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Sample records for strongest activity ec50

  1. Ketone EC50 values in the Microtox test.

    Science.gov (United States)

    Chen, H F; Hee, S S

    1995-03-01

    The Microtox EC50 values for the following ketones are reported in the following homologous series: straight chain methyl ketones (acetone, 2-butanone, 2-pentanone, 2-hepatonone, 2-octanone, 2-decanone, and 2-tridecanone); methyl ketones substituted at one alpha carbon (3-methyl-2-butanone; 3,3-dimethyl-2-butanone); methyl substituted at two alpha carbons (2,4-dimethyl-3-pentanone; 2,2,4,4-tetramethyl-3-pentanone); phenyl groups replacing methyl in acetone (acetophenone; benzophenone); methyl groups substituted at the alpha carbons of cyclohexanone; and 2,3- 2,4-, and 2,5-hexanediones, most for the first time. While there were linear relationships between log EC50 and MW for the straight chain methyl ketones, and for methyl substitution at the alpha carbon for methyl ketones, there were no other linear relationships. As molecular weight increased, the EC50 values of soluble ketones decreased; as distance between two carbonyl groups decreased so too did EC50 values. Thus, for the ketones the geometry around the carbonyl group is an important determinant of toxicity as well as MW, water solubility, and octanol/water coefficient.

  2. Annona muricata leaves have strongest cytotoxic activity against breast cancer cells

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    Susi Endrini

    2014-12-01

    Full Text Available Background Plant-derived herbal compounds have a long history of clinical use, better patient tolerance and acceptance. They are freely available natural compounds that can be safely used to prevent various ailments. Plants have been the basis of traditional medicine throughout the world for thousands of years and are providing mankind with new remedies. The objective of this study was to determine the cytotoxicity of soursop (Anona muricata Linn leaves and pearl grass (Hedyotis corymbosa (L. Lam. on the hormone-dependent human breast carcinoma Michigan Cancer Foundation-7 (MCF-7 cell line. Methods This study used two types of solvents (water and ethanol in the extraction process and two incubation times (24 hours and 48 hours in the MTT assays to analyze the cytotoxic effects of both plants. Results Preliminary results showed that the ethanolic extract of soursop leaves (SE displayed cytotoxic effects against MCF-7 on 24- and 48-hour incubation times with IC50 values of 88.788 ìg/ml and 14.678 mg/ml, respectively. Ethanolic pearl grass extract (PE showed similar results, with IC50 values of 65.011 mg/ml on 24-hour incubation time and 52.329 mg/ml on 48-hour incubation time against MCF-7 cell line. However, the water extract of both plants displayed lower cytotoxic effect against MCF-7 cell line. Conclusion The ethanolic extract of both plants displayed cytotoxic effect against MCF-7. Soursop (Anona muricata Linn leaves have the strongest cytotoxic activity against MCF-7 breast cancer cell line.

  3. Annona muricata leaves have strongest cytotoxic activity against breast cancer cells

    Directory of Open Access Journals (Sweden)

    Susi Endrini

    2015-12-01

    Full Text Available BACKGROUND Plant-derived herbal compounds have a long history of clinical use, better patient tolerance and acceptance. They are freely available natural compounds that can be safely used to prevent various ailments. Plants have been the basis of traditional medicine throughout the world for thousands of years and are providing mankind with new remedies. The objective of this study was to determine the cytotoxicity of soursop (Anona muricata Linn leaves and pearl grass (Hedyotis corymbosa (L. Lam. on the hormone-dependent human breast carcinoma Michigan Cancer Foundation-7 (MCF-7 cell line. METHODS This study used two types of solvents (water and ethanol in the extraction process and two incubation times (24 hours and 48 hours in the MTT assays to analyze the cytotoxic effects of both plants. RESULTS Preliminary results showed that the ethanolic extract of soursop leaves (SE displayed cytotoxic effects against MCF-7 on 24- and 48-hour incubation times with IC50 values of 88.788 μg/ml and 14.678 μg/ml, respectively. Ethanolic pearl grass extract (PE showed similar results, with IC50 values of 65.011 μg/ ml on 24-hour incubation time and 52.329 μg/ml on 48-hour incubation time against MCF-7 cell line. However, the water extract of both plants displayed lower cytotoxic effect against MCF-7 cell line. CONCLUSION The ethanolic extract of both plants displayed cytotoxic effect against MCF-7. Soursop (Anona muricata Linn leaves have the strongest cytotoxic activity against MCF-7 breast cancer cell line.

  4. ICECAP: an integrated, general-purpose, automation-assisted IC50/EC50 assay platform.

    Science.gov (United States)

    Li, Ming; Chou, Judy; King, Kristopher W; Jing, Jing; Wei, Dong; Yang, Liyu

    2015-02-01

    IC50 and EC50 values are commonly used to evaluate drug potency. Mass spectrometry (MS)-centric bioanalytical and biomarker labs are now conducting IC50/EC50 assays, which, if done manually, are tedious and error-prone. Existing bioanalytical sample preparation automation systems cannot meet IC50/EC50 assay throughput demand. A general-purpose, automation-assisted IC50/EC50 assay platform was developed to automate the calculations of spiking solutions and the matrix solutions preparation scheme, the actual spiking and matrix solutions preparations, as well as the flexible sample extraction procedures after incubation. In addition, the platform also automates the data extraction, nonlinear regression curve fitting, computation of IC50/EC50 values, graphing, and reporting. The automation-assisted IC50/EC50 assay platform can process the whole class of assays of varying assay conditions. In each run, the system can handle up to 32 compounds and up to 10 concentration levels per compound, and it greatly improves IC50/EC50 assay experimental productivity and data processing efficiency. © 2014 Society for Laboratory Automation and Screening.

  5. Mathematical modeling improves EC50 estimations from classical dose-response curves.

    Science.gov (United States)

    Nyman, Elin; Lindgren, Isa; Lövfors, William; Lundengård, Karin; Cervin, Ida; Sjöström, Theresia Arbring; Altimiras, Jordi; Cedersund, Gunnar

    2015-03-01

    The β-adrenergic response is impaired in failing hearts. When studying β-adrenergic function in vitro, the half-maximal effective concentration (EC50 ) is an important measure of ligand response. We previously measured the in vitro contraction force response of chicken heart tissue to increasing concentrations of adrenaline, and observed a decreasing response at high concentrations. The classical interpretation of such data is to assume a maximal response before the decrease, and to fit a sigmoid curve to the remaining data to determine EC50 . Instead, we have applied a mathematical modeling approach to interpret the full dose-response curve in a new way. The developed model predicts a non-steady-state caused by a short resting time between increased concentrations of agonist, which affect the dose-response characterization. Therefore, an improved estimate of EC50 may be calculated using steady-state simulations of the model. The model-based estimation of EC50 is further refined using additional time-resolved data to decrease the uncertainty of the prediction. The resulting model-based EC50 (180-525 nm) is higher than the classically interpreted EC50 (46-191 nm). Mathematical modeling thus makes it possible to re-interpret previously obtained datasets, and to make accurate estimates of EC50 even when steady-state measurements are not experimentally feasible. The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database, and may be accessed at http://jjj.bio.vu.nl/database/nyman. © 2015 FEBS.

  6. The dynamics of competitive activity performance of the strongest athletes in the world during the Olympic year

    Directory of Open Access Journals (Sweden)

    Rabin Muhammad Fahmi

    2016-12-01

    Full Text Available The paper scrutinizes the annual dynamics of competitive activity performance of prize winners in track and field of the Games of the XXXI Olympiad in Rio de Janeiro. The studies performed allow to identify two basic strategies of participation of elite athletes in the competitions. The first implies a strong focus on achieving the best results in major competitions of the year. It is used by most of the strongest athletes in the world. The second focuses the athlete on the effective combination of competitive activity in major competitions of the year (the Olympics and World Championships and in the Diamond League. As shown by the experience of the best sports practice, only a limited number of athletes manage to implement the latter strategy. The methodological approaches to planning competitive activity during the year are identified. The first involves the rational allocation of the optimal number of competitions throughout the year, the second focuses on preparatory competitive activities of a fairly high intensity, and the third involves the use of a small number of competitions in the system of annual training.

  7. In vitro antiviral activities of Caesalpinia pulcherrima and its related flavonoids.

    Science.gov (United States)

    Chiang, L C; Chiang, W; Liu, M C; Lin, C C

    2003-08-01

    The aim of this study was to search for new antiviral agents from Chinese herbal medicine. Pure flavonoids and aqueous extracts of Caesalpinia pulcherrima Swartz were used in experiments to test their influence on a series of viruses, namely herpesviruses (HSV-1, HSV-2) and adenoviruses (ADV-3, ADV-8, ADV-11). The EC50 was defined as the concentration required to achieve 50% protection against virus-induced cytopathic effects, and the selectivity index (SI) was determined as the ratio of CC50 (concentration of 50% cellular cytotoxicity) to EC50. Results showed that aqueous extracts of C. pulcherrima and its related quercetin possessed a broad-spectrum antiviral activity. Among them, the strongest activities against ADV-8 were fruit and seed (EC50 = 41.2 mg/l, SI = 83.2), stem and leaf (EC50 = 61.8 mg/l, SI = 52.1) and flower (EC50 = 177.9 mg/l, SI = 15.5), whereas quercetin possessed the strongest anti-ADV-3 activity (EC50 = 24.3 mg/l, SI = 20.4). In conclusion, some compounds of C. pulcherrima which possess antiviral activities may be derived from the flavonoid of quercetin. The mode of action of quercetin against HSV-1 and ADV-3 was found to be at the early stage of multiplication and with SI values greater than 20, suggesting the potential use of this compound for treatment of the infection caused by these two viruses.

  8. Analysis of the competitive activities of Ukrainian champions with the strongest fighters of world (based on world championship in Greco-Roman wrestling in 2011

    Directory of Open Access Journals (Sweden)

    Radchenko Y.А.

    2012-06-01

    Full Text Available The comparative analysis of results of competition activity of the strongest fighters is presented Greco-Roman style on a world of 2011 cup. Found out some tendencies and conformities to the law in application technical tactical actions by fighters in a competition duel on the modern stage of development to Greco-Roman fight. It is set that in most cases sportsmen won due to ability to win with insignificant advantage for all of competitors. They most adjusted to the modern requirements of conduct of duel, conduct an active fight and own effective attacking receptions, reliably they are applied and rarely attack without an estimation. One of more effective receptions in an orchestra there is defence of fighter which is down. Found out failings in preparation of the Ukrainian sportsmen can underlie correction of the programs of preparation to the Olympic games. It is recommended to utillize the resulted information for the design of the special trainings tasks which are conditioned the individual features of separate sportsmen.

  9. The median effective concentration (EC50) of propofol with different doses of fentanyl during colonoscopy in elderly patients.

    Science.gov (United States)

    Li, Shiyang; Yu, Fang; Zhu, Huichen; Yang, Yuting; Yang, Liqun; Lian, Jianfeng

    2016-04-21

    Propofol and fentanyl are the most widely administered anesthesia maintaining drugs during colonoscopy. In this study, we determined the median effective concentration (EC50) of propofol required for colonoscopy in elderly patients, and the purpose of this study was to describe the pharmacodynamic interaction between fentanyl and propofol when used in combination for colonoscopy in elderly patients. Ninety elderly patients scheduled for colonoscopy were allocated into three groups in a randomized, double-blinded manner as below, F0.5 group (0.5 μg.kg(-1) fentanyl), F1.0 group (1.0 μg.kg(-1) fentanyl) and saline control group. Anaesthesia was achieved by target-controlled infusion of propofol (Marsh model, with an initial plasma concentration of 2.0 μg.ml(-1)) and fentanyl. Colonoscopy was started 3 min after the injection of fentanyl. The EC50 of propofol for colonoscopy with different doses of fentanyl was measured by using an up-and-down sequential method with an adjacent concentration gradient at 0.5 μg.ml(-1) to inhibit purposeful movements. Anaesthesia associated adverse events and recovery characters were also recorded. The EC50 of propofol for colonoscopy in elderly patients were 2.75 μg.ml(-1) (95% CI, 2.50-3.02 μg.ml(-1)) in F0.5 group, 2.05 μg.ml(-1) (95% CI, 1.98-2.13 μg.ml(-1)) in F1.0 group and 3.08 μg.ml(-1) (95% CI, 2.78-3.42 μg.ml(-1)) in control group respectively (P fentanyl up to 1.0 μg.kg(-1) reduces the propofol EC50 required for elderly patients undergoing colonoscopy, and there was no significant difference in anaesthesia associated adverse events but prolonged awake and discharge time. Chinese Clinical Trial Registry ChiCTR15006368. Date of registration: May 3, 2015.

  10. Acute toxicity of heavy metals to acetate-utilizing mixed cultures of sulfate-reducing bacteria: EC100 and EC50.

    Science.gov (United States)

    Utgikar, V P; Chen, B Y; Chaudhary, N; Tabak, H H; Haines, J R; Govind, R

    2001-12-01

    Acid mine drainage from abandoned mines and acid mine pit lakes is an important environmental concern and usually contains appreciable concentrations of heavy metals. Because sulfate-reducing bacteria (SRB) are involved in the treatment of acid mine drainage, knowledge of acute metal toxicity levels for SRB is essential for the proper functioning of the treatment system for acid mine drainage. Quantification of heavy metal toxicity to mixed cultures of SRB is complicated by the confounding effects of metal hydroxide and sulfide precipitation, biosorption, and complexation with the constituents of the reaction matrix. The objective of this paper was to demonstrate that measurements of dissolved metal concentrations could be used to determine the toxicity parameters for mixed cultures of sulfate-reducing bacteria. The effective concentration, 100% (EC100), the lowest initial dissolved metal concentrations at which no sulfate reduction is observed, and the effective concentration, 50% (EC50), the initial dissolved metal concentrations resulting in a 50% decrease in sulfate reduction, for copper and zinc were determined in the present study by means of nondestructive, rapid physical and chemical analytical techniques. The reaction medium used in the experiments was designed specifically (in terms of pH and chemical composition) to provide the nutrients necessary for the sulfidogenic activity of the SRB and to preclude chemical precipitation of the metals under investigation. The toxicity-mitigating effects of biosorption of dissolved metals were also quantified. Anaerobic Hungate tubes were set up (at least in triplicate) and monitored for sulfate-reduction activity. The onset of SRB activity was detected by the blackening of the reaction mixture because of formation of insoluble ferrous sulfide. The EC100 values were found to be 12 mg/L for copper and 20 mg/L for zinc. The dissolved metal concentration measurements were effective as the indicators of the effect of the

  11. Acute toxicity of metals and reference toxicants to a freshwater ostracod, Cypris subglobosa Sowerby, 1840 and correlation to EC50 values of other test models

    International Nuclear Information System (INIS)

    Khangarot, B.S.; Das, Sangita

    2009-01-01

    The ostracod Cypris subglobosa Sowerby, 1840 static bioassay test on the basis of a 48 h of 50% of immobilization (EC 50 ) has been used to measure the toxicity of 36 metals and metalloids and 12 reference toxicants. Among the 36 metals and metalloids, osmium (Os) was found to be the most toxic in the test while boron (B), the least toxic. The EC 50 values of this study revealed positive linear relationship with the established test models of cladoceran (Daphnia magna), sludge worm (Tubifex tubifex), chironomid larvae (Chironomus tentans), protozoan (Tetrahymena pyriformis), fathead minnow (Pimephales promelas), bluegill sunfish (Lepomis macrochirus), and aquatic macrophyte duckweed (Lemna minor). Correlation coefficients (r 2 ) for 17 physicochemical properties of metals or metal ions and EC 50 s (as pM) were examined by linear regression analysis. The electronegativity, ionization potential, melting point, solubility product of metal sulfides (pK sp ), softness parameter and some other physicochemical characteristics were significantly correlated with EC 50 s of metals to C. subglobosa. The reproducibility of toxicity test was determined using 12 reference toxicants. The coefficient of variability of the EC 50 s ranged from 6.95% to 55.37% and variability was comparable to that noticed for D. magna and other aquatic test models. The study demonstrated the need to include crustacean ostracods in a battery of biotests to detect the presence of hazardous chemicals in soils, sewage sludges, sediments and aquatic systems.

  12. The Strongest Magnetic Field in Sunspots

    Science.gov (United States)

    Okamoto, J.; Sakurai, T.

    2017-12-01

    Sunspots are concentrations of magnetic fields on the solar surface. Generally, the strongest magnetic field in each sunspot is located in the dark umbra in most cases. A typical field strength in sunspots is around 3,000 G. On the other hand, some exceptions also have been found in complex sunspots with bright regions such as light bridges that separate opposite polarity umbrae, for instance with a strength of 4,300 G. However, the formation mechanism of such strong fields outside umbrae is still puzzling. Here we report an extremely strong magnetic field in a sunspot, which was located in a bright region sandwiched by two opposite-polarity umbrae. The strength is 6,250 G, which is the largest ever observed since the discovery of magnetic field on the Sun in 1908 by Hale. We obtained 31 scanned maps of the active region observed by Hinode/SOT/SP with a cadence of 3 hours over 5 days (February 1-6, 2014). Considering the spatial and temporal evolution of the vector magnetic field and the Doppler velocity in the bright region, we suggested that this strong field region was generated as a result of compression of one umbra pushed by the outward flow from the other umbra (Evershed flow), like the subduction of the Earth's crust in plate tectonics.

  13. Linking algal growth inhibition to chemical activity

    DEFF Research Database (Denmark)

    Schmidt, Stine N.; Mayer, Philipp

    2015-01-01

    for baseline toxicity. First, the reported effective concentrations (EC50) were divided by the respective water solubilities (Swater), since the obtained EC50/Swater ratio essentially equals the effective chemical activity (Ea50). The majority of EC50/Swater ratios were within the expected chemical activity...

  14. Anti-citrullinated peptide antibodies are the strongest predictor of clinically relevant radiographic progression in rheumatoid arthritis patients achieving remission or low disease activity: A post hoc analysis of a nationwide cohort in Japan.

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    Tomohiro Koga

    Full Text Available To determine prognostic factors of clinically relevant radiographic progression (CRRP in patients with rheumatoid arthritis (RA achieving remission or low disease activity (LDA in clinical practice.Using data from a nationwide, multicenter, prospective study in Japan, we evaluated 198 biological disease-modifying antirheumatic drug (bDMARD-naïve RA patients who were in remission or had LDA at study entry after being treated with conventional synthetic DMARDs (csDMARDs. CRRP was defined as the yearly progression of modified total Sharp score (mTSS >3.0 U. We performed a multiple logistic regression analysis to explore the factors to predict CRRP at 1 year. We used receiver operating characteristic (ROC curve to estimate the performance of relevant variables for predicting CRRP.The mean Disease Activity Score in 28 joints-erythrocyte sedimentation rate (DAS28-ESR was 2.32 ± 0.58 at study entry. During the 1-year observation, remission or LDA persisted in 72% of the patients. CRRP was observed in 7.6% of the patients. The multiple logistic regression analysis revealed that the independent variables to predict the development of CRRP were: anti-citrullinated peptide antibodies (ACPA positivity at baseline (OR = 15.2, 95%CI 2.64-299, time-integrated DAS28-ESR during the 1 year post-baseline (7.85-unit increase, OR = 1.83, 95%CI 1.03-3.45, and the mTSS at baseline (13-unit increase, OR = 1.22, 95%CI 1.06-1.42.ACPA positivity was the strongest independent predictor of CRRP in patients with RA in remission or LDA. Physicians should recognize ACPA as a poor-prognosis factor regarding the radiographic outcome of RA, even among patients showing a clinically favorable response to DMARDs.

  15. The strongest magnetic fields in the universe

    CERN Document Server

    Balogh, A; Falanga, M; Lyutikov, M; Mereghetti, S; Piran, T; Treumann, RA

    2016-01-01

    This volume extends the ISSI series on magnetic fields in the Universe into the domain of what are by far the strongest fields in the Universe, and stronger than any field that could be produced on Earth. The chapters describe the magnetic fields in non-degenerate strongly magnetized stars, degenerate stars (such as white dwarfs and neutron stars), exotic members called magnetars, and in their environments, as well as magnetic fields in the environments of black holes. These strong fields have a profound effect on the behavior of matter, visible in particular in highly variable processes like radiation in all known wavelengths, including Gamma-Ray bursts. The generation and structure of such strong magnetic fields and effects on the environment are also described.

  16. Salomon: '97 E and P looking strongest in 9 years

    International Nuclear Information System (INIS)

    Anon.

    1997-01-01

    Based on companies' disclosed spending plans, 1997 is shaping up to be the strongest year-ahead outlook in 9 years, according to Salomon Bros. Inc. Salomon Bros.' conclusion stems from its 15th annual survey of worldwide oil and gas exploration and production spending. The survey, released last month, included 125 US independents, 97 Canadian companies, 103 companies outside the US and Canada, and 15 majors. Significantly, when the 15% growth experienced in 1996 is combined with the 1997 outlook, it represents the strongest indicator of 2-year activity in the past 15 years, said Salomon Bros. Double-digit spending growth is projected in all regions for 1997, the analyst said. Salomon Bros. said a higher percentage of companies' E and P budgets are being allocated to offshore projects, driven in part by attractive prospects, 3D seismic technology, and increased operational efficiencies

  17. HPLC PROFILING OF PHENOLIC ACIDS AND FLAVONOIDS AND EVALUATION OF ANTI-LIPOXYGENASE AND ANTIOXIDANT ACTIVITIES OF AQUATIC VEGETABLE LIMNOCHARIS FLAVA.

    Science.gov (United States)

    Ooh, Keng-fei; Ong, Hean-Chooi; Wong, Fai-Chu; Chai, Tsun-Thai

    2015-01-01

    Limnocharis flava is an edible wetland plant, whose phenolic acid and flavonoid compositions as well as bioactivities were underexplored. This study analyzed the profiles of selected hydroxybenzoic acids, hydroxycinnamic acids and flavonoids in the aqueous extracts of L. flava leaf, rhizome and root by high performance liquid chromatography (HPLC). Anti-lipoxygenase and antioxidant (iron chelating, 2,2-diphenyl-l-picrylhydrazyl (DPPH) radical scavenging, and nitric oxide (NO) scavenging) activities of the extracts were also evaluated. Leaf extract had the highest phenolic contents, being most abundant in p-hydroxybenzoic acid (3861.2 nmol/g dry matter), ferulic acid (648.8 nmol/g dry matter), and rutin (4110.7 nmol/g dry matter). Leaf extract exhibited the strongest anti-lipoxygenase (EC50 6.47 mg/mL), iron chelating (EC50 6.65 mg/mL), DPPH scavenging (EC50 15.82 mg/mL) and NO scavenging (EC50 3.80 mg/mL) activities. Leaf extract also had the highest ferric reducing ability. This is the most extensive HPLC profiling of phenolic acids and flavonoids in L.flava to date. In conclusion, L. flava leaf is a source of health-promoting phenolics, anti-lipoxygenase agents and antioxidants.

  18. Fractionation and antioxidant activity potency of the extract of Garcinia lateriflora Blume var. javanica Boerl leaf

    Science.gov (United States)

    Mahayasih, Putu Gita Maya Widyaswari; Elya, Berna; Hanafi, Muhammad

    2018-02-01

    Garcinia lateriflora leaves extract of the family Guttiferae has been known to have excellent antioxidant activity. The objective of the study was to determine the antioxidant effect of the n-hexane, ethyl acetate and methanol extracts of G. lateriflora leaves extract. The antioxidant activity was determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging methods and Feric Reducing Antioxidant Power (FRAP) to determine the antioxidant properties. The extracts were fractionated by using column chromatography. The Methanol extract exhibited the strongest antioxidant activity with EC50 values are 13.95 and 19.65 µg/mL by DPPH and FRAP methods respectively. E13 fraction was the most active fraction from ethyl acetate extract with EC50 value for DPPH scavenging method was 37.14 µg/mL and 34.46 µg/mL for reducing power by the FRAP method. Meanwhile M3 fraction was the most active fraction in methanol extract with EC50 value for DPPH scavenging method was 50.02 µg/mL and 37.32 µg/mL for reducing power by the FRAP method.

  19. Antimicrobial activities of pyridinium-tailored pyrazoles bearing 1,3,4-oxadiazole scaffolds

    Directory of Open Access Journals (Sweden)

    Lei Zhou

    2017-11-01

    Full Text Available Herein, a series of pyridinium-tailored 5-trifluoromethylpyrazoles containing 1,3,4-oxadiazole moieties were constructed through coupling key pharmaceutical fragments of pyridinium, pyrazole, and 1,3,4-oxadiazole scaffolds in single molecular architecture. Antimicrobial results suggested that this kind of compounds exhibited significant activities against three types of pathogenic bacteria and six fungal strains in vitro. The minimal EC50 values of designed compounds against Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri could reach to 0.467, 1.04, and 0.600 μg/mL, respectively, through tuning and optimizing N-substituents, bridging atom, and alkyl length of the tailor. Antifungal assays revealed that all title molecules possessed considerable activity against Botrytis cinerea with the minimal EC50 value up to 2.71 μg/mL; and compounds I-8, I-10, I-12, II-12, and IV-12 showed the strongest growth suppression toward Rhizoctonia solani with EC50 values ranging from 10.2 to 24.0 μg/mL. Given the above results, this kind of compounds could serve as new lead compounds in the research of antimicrobial chemotherapy.

  20. The Strength of the Strongest Ties in Collaborative Problem Solving

    DEFF Research Database (Denmark)

    de Montjoye, Yves-Alexandre; Stopczynski, Arkadiusz; Shmueli, Erez

    2014-01-01

    Complex problem solving in science, engineering, and business has become a highly collaborative endeavor. Teams of scientists or engineers collaborate on projects using their social networks to gather new ideas and feedback. Here we bridge the literature on team performance and information networks...... by studying teams' problem solving abilities as a function of both their within-team networks and their members' extended networks. We show that, while an assigned team's performance is strongly correlated with its networks of expressive and instrumental ties, only the strongest ties in both networks have...... an effect on performance. Both networks of strong ties explain more of the variance than other factors, such as measured or self-evaluated technical competencies, or the personalities of the team members. In fact, the inclusion of the network of strong ties renders these factors non...

  1. The Strength of the Strongest Ties in Collaborative Problem Solving

    Science.gov (United States)

    de Montjoye, Yves-Alexandre; Stopczynski, Arkadiusz; Shmueli, Erez; Pentland, Alex; Lehmann, Sune

    2014-06-01

    Complex problem solving in science, engineering, and business has become a highly collaborative endeavor. Teams of scientists or engineers collaborate on projects using their social networks to gather new ideas and feedback. Here we bridge the literature on team performance and information networks by studying teams' problem solving abilities as a function of both their within-team networks and their members' extended networks. We show that, while an assigned team's performance is strongly correlated with its networks of expressive and instrumental ties, only the strongest ties in both networks have an effect on performance. Both networks of strong ties explain more of the variance than other factors, such as measured or self-evaluated technical competencies, or the personalities of the team members. In fact, the inclusion of the network of strong ties renders these factors non-significant in the statistical analysis. Our results have consequences for the organization of teams of scientists, engineers, and other knowledge workers tackling today's most complex problems.

  2. Strongest gravitational waves from neutrino oscillations at supernova core bounce

    International Nuclear Information System (INIS)

    Mosquera Cuesta, H.J.; Fiuza, K.

    2004-01-01

    Resonant active-to-active (ν a →ν a ), as well as active-to-sterile (ν a →ν s ) neutrino (ν) oscillations can take place during the core bounce of a supernova collapse. Besides, over this phase, weak magnetism increases the antineutrino (anti ν) mean free path, and thus its luminosity. Because the oscillation feeds mass-energy into the target ν species, the large mass-squared difference between the species (ν a →ν s ) implies a huge amount of energy to be given off as gravitational waves (L GW ∝10 49 erg s -1 ), due to anisotropic but coherent ν flow over the oscillation length. This asymmetric ν-flux is driven by both the spin-magnetic and the universal spin-rotation coupling. The novel contribution of this paper stems from (1) the new computation of the anisotropy parameter α∝0.1-0.01, and (2) the use of the tight constraints from neutrino experiments as SNO and KamLAND, and the cosmic probe WMAP, to compute the gravitational-wave emission during neutrino oscillations in supernovae core collapse and bounce. We show that the mass of the sterile neutrino ν s that can be resonantly produced during the flavor conversions makes it a good candidate for dark matter as suggested by Fuller et al., Phys. Rev. D 68, 103002 (2003). The new spacetime strain thus estimated is still several orders of magnitude larger than those from ν diffusion (convection and cooling) or quadrupole moments of neutron star matter. This new feature turns these bursts into the more promising supernova gravitational-wave signals that may be detected by observatories as LIGO, VIRGO, etc., for distances far out to the VIRGO cluster of galaxies. (orig.)

  3. The Philippine tobacco industry: "the strongest tobacco lobby in Asia".

    Science.gov (United States)

    Alechnowicz, K; Chapman, S

    2004-12-01

    To highlight revelations from internal tobacco industry documents about the conduct of the industry in the Philippines since the 1960s. Areas explored include political corruption, health, employment of consultants, resisting pack labelling, and marketing and advertising. Systematic keyword Minnesota depository website searches of tobacco industry internal documents made available through the Master Settlement Agreement. The Philippines has long suffered a reputation for political corruption where collusion between state and business was based on the exchange of political donations for favourable economic policies. The tobacco industry was able to limit the effectiveness of proposed anti-tobacco legislation. A prominent scientist publicly repudiated links between active and passive smoking and disease. The placement of health warning labels was negotiated to benefit the industry, and the commercial environment allowed it to capitalise on their marketing freedoms to the fullest potential. Women, children, youth, and the poor have been targeted. The politically laissez faire Philippines presented tobacco companies with an environment ripe for exploitation. The Philippines has seen some of the world's most extreme and controversial forms of tobacco promotion flourish. Against international standards of progress, the Philippines is among the world's slowest nations to take tobacco control seriously.

  4. Create positive contraceptive images for strongest impact in single lesson.

    Science.gov (United States)

    1987-05-01

    Health educators attempting to deliver contraceptive information to adolescents in the classroom must seek ways to make a major impact in a very short period of time. A Planned Parenthood professional from New Jersey has developed a single-shot birth control lesson that, rather than presenting the pros and cons of various contraceptive methods, has teenagers identify themselves as at high, low, or no risk of pregnancy. Students estimate the number of classmates who are in each category and then assess whether they personally are at risk of an unintended pregnancy. In general, teens overestimate the number of classmates who are sexually active. This approach seems to make the ensuing discussion of contraceptive methods more meaningful. This discussion presents the condom and foam, the sponge, and visiting a family planning clinic. After this 40 minute presentation, fewer adolescents report being afraid of contraceptive side effects; they also have more knowledge about the efficacy and availability of different methods. A lesson in preparation is centered around a videotape entitled "Swept Away is Not Okay." It shows a teen couple going to a family planning clinic before they ever have intercourse. This strategy of encouraging adolescents to seek contraception before sexual involvement begins is considered more realistic than pressuring teens to abstain from sex. School officials and teachers have been receptive to this educational approach, viewing it as presenting important public health information.

  5. Toxicities of triclosan, phenol, and copper sulfate in activated sludge.

    Science.gov (United States)

    Neumegen, Rosalind A; Fernández-Alba, Amadeo R; Chisti, Yusuf

    2005-04-01

    The effect of toxicants on the BOD degradation rate constant was used to quantitatively establish the toxicity of triclosan, phenol, and copper (II) against activated sludge microorganisms. Toxicities were tested over the following ranges of concentrations: 0-450 mg/L for phenol, 0-2 mg/L for triclosan, and 0-35 mg/L for copper sulfate (pentahydrate). According to the EC(50) values, triclosan was the most toxic compound tested (EC(50) = 1.82 +/- 0.1 mg/L), copper (II) had intermediate toxicity (EC(50) = 18.3 +/- 0.37 mg/L), and phenol was the least toxic (EC(50) = 270 +/- 0.26 mg/L). The presence of 0.2% DMSO had no toxic effect on the activated sludge. The toxicity evaluation method used was simple, reproducible, and directly relevant to activated sludge wastewater treatment processes.

  6. Strongest Tropical cyclones: 1980-2009: A 30-year collage of Hurricane Satellite (HURSAT) data

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Strongest Tropical Cyclones: 1980-2009 poster - a 30-year collage of Hurricane Satellite (HURSAT) data. This poster depicts a series of 5 degree grids where within...

  7. The Dual Antimelanogenic and Antioxidant Activities of the Essential Oil Extracted from the Leaves of Acorus macrospadiceus (Yamamoto F. N. Wei et Y. K. Li

    Directory of Open Access Journals (Sweden)

    Huey-Chun Huang

    2012-01-01

    Full Text Available The antimelanogenic and antioxidant activities of the essential oil extracted from the leaves of Acorus macrospadiceus (Yamamoto F. N. Wei et Y. K. Li have never been explored. The essential oil effectively inhibited mushroom tyrosinase activity (EC50 = 1.57 mg/mL and B16F10 tyrosinase activity (IC50 = 1.01 mg/mL, decreased the melanin content (EC50 = 1.04 mg/mL, and depleted the cellular level of the reactive oxygen species (ROS (EC50 = 1.87 mg/mL. The essential oil effectively scavenged 2,2-diphenyl-1-picryl-hydrazyl (DPPH (EC50 = 0.121 mg/mL and 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid ABTS+ radicals (EC50 = 0.122 mg/mL. It also exhibited an apparent reducing power (EC50 = 0.021 mg/mL and metal-ion chelating activity (EC50 = 0.029 mg/mL. The chemical constituents of the essential oil are ethers (55.73%, ketones (19.57%, monoterpenes (7.82%, alcohols (3.85%, esters (3.77%, sesquiterpenes (3.72%, and aromatic compounds (2.85%. The results confirm that A. macrospadiceus essential oil is a natural antioxidant and inhibitor of melanogenesis.

  8. The Dual Antimelanogenic and Antioxidant Activities of the Essential Oil Extracted from the Leaves of Acorus macrospadiceus (Yamamoto) F. N. Wei et Y. K. Li

    Science.gov (United States)

    Huang, Huey-Chun; Wang, Hsiao-Fen; Yih, Kuang-Hway; Chang, Long-Zen; Chang, Tsong-Min

    2012-01-01

    The antimelanogenic and antioxidant activities of the essential oil extracted from the leaves of Acorus macrospadiceus (Yamamoto) F. N. Wei et Y. K. Li have never been explored. The essential oil effectively inhibited mushroom tyrosinase activity (EC50 = 1.57 mg/mL) and B16F10 tyrosinase activity (IC50 = 1.01 mg/mL), decreased the melanin content (EC50 = 1.04 mg/mL), and depleted the cellular level of the reactive oxygen species (ROS) (EC50 = 1.87 mg/mL). The essential oil effectively scavenged 2,2-diphenyl-1-picryl-hydrazyl (DPPH) (EC50 = 0.121 mg/mL) and 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) ABTS+ radicals (EC50 = 0.122 mg/mL). It also exhibited an apparent reducing power (EC50 = 0.021 mg/mL) and metal-ion chelating activity (EC50 = 0.029 mg/mL). The chemical constituents of the essential oil are ethers (55.73%), ketones (19.57%), monoterpenes (7.82%), alcohols (3.85%), esters (3.77%), sesquiterpenes (3.72%), and aromatic compounds (2.85%). The results confirm that A. macrospadiceus essential oil is a natural antioxidant and inhibitor of melanogenesis. PMID:23304214

  9. ON POTENTIAL REPRESENTATIONS OF THE DISTRIBUTION LAW OF RARE STRONGEST EARTHQUAKES

    Directory of Open Access Journals (Sweden)

    M. V. Rodkin

    2014-01-01

    'bend-down' is described by the finite distribution law, i.e. the bend-down occurs more efficiently than it is envisaged in the commonly used model developed by Y. Kagan (which treats the bend-dawn as an exponential decay law. However, despite the finiteness of the distribution law, density of magnitudes decline quite slowly in the area close to the maximum possible Мmах event as (Мmах – Mn, where n varies in the range between 4 and 6 in the majority of cases. As a result Мmах value can be estimated only with a large error. In rare cases, if the space-and-time area under study contains higher number of strongest earthquakes, the empirical distribution law becomes close to the exponential law; in this case n value is quite high, and Мmах values becomes unstable and tend to infinite growth.In our study, the distribution law of strongest earthquakes was investigated by the methods based on the extreme values theory (world data and several regional catalogues were examined, and the results of calculation do not reveal cases of  occurrence of characteristic events. However, such a seismic regime was revealed in a number of cases from paleoseismicity data and from some instrumental regional catalogues. Conditions providing for the occurrence of characteristic earthquakes are studied here using the multiplicative cascade model. According to [Rodkin, 2011], this model provides the simulation of all known regularities of seismic regime, such as a decrease in b-value in the vicinity of strong earthquakes, development of aftershock power cascade, and existence of seismic cycle and foreshock activity. This article considers an extension of the cascade model by adding of non-linear members in the kinetic cascade equation in order to describe effects of the 'bend-down' of the earthquake recurrence curve and the characteristic earthquakes occurrence. It is shown that in terms of the multiplicative cascade model, the occurrence of characteristic earthquakes is connected

  10. Homoisoflavonoids and Chalcones Isolated from Haematoxylum campechianum L., with Spasmolytic Activity

    Directory of Open Access Journals (Sweden)

    Armando Escobar-Ramos

    2017-08-01

    Full Text Available Haematoxylum campechianum is a medicinal plant employed as an astringent to purify the blood and to treat stomach problems such as diarrhea and dysentery. A bio-guided chemical fractionation of the methanolic extract obtained from this plant allowed for the isolation of five compounds: two chalcones known as sappanchalcone (1; 3-deoxysappanchalcone (2; three homoisoflavonoids known as hematoxylol A (3; 4-O-methylhematoxylol (4; and, hematoxin (5. The spasmolytic activity was determined in an in vitro model (electrically induced contractions of guinea pig ileum, and allowed to demonstrate that the methanolic extract (EC50 = 62.11 ± 3.23 fractions HcF7 (EC50 = 61.75 ± 3.55 and HcF9 (EC50 = 125.5 ± 10.65 and compounds 1 (EC50 = 16.06 ± 2.15 and 2 (EC50 = 25.37 ± 3.47 of Haematoxylum campechianum present significant relaxing activity as compared to papaverine (EC50 = 20.08 ± 2.0 as a positive control.

  11. Antioxidant, Antitubercular and Cytotoxic Activities of Piper imperiale

    Directory of Open Access Journals (Sweden)

    Sanjib Bhakta

    2012-04-01

    Full Text Available Phenolic compounds are widely distributed in Nature and act as pharmacologically active constituents in many herbal medicines. They have multiple biological properties, most notably antioxidant, antibacterial and cytotoxic activities. In the present study an attempt to correlate the phenolic composition of leaf, flower and wood extracts of Piper imperiale, with antioxidant, antitubercular and cytotoxic activities was undertaken. The total phenol content ranged from 1.98 to 6.94 mg GAE/gDW among ethanolic extracts, and gallic acid, catechin, epicatechin, ferulic acid, resveratrol and quercetin were identified and quantified by HPLC. DPPH and ABTS assays showed high antioxidant activity of the leaf extract (EC50ABTS = 15.6 µg/mL, EC50DPPH = 27.3 µg/mL with EC50 in the same order of magnitude as the hydroxyquinone (EC50ABTS = 10.2 µg/mL, EC50DPPH = 15.7 µg/mL. The flower extract showed strong antimicrobial activity against Mycobacterium tuberculosis H37Rv. All the extracts exhibited dose-dependent cytotoxic effects against MCF-7 cancer cells. This is the first time that a Piper extract has been found to be highly active against M. tuberculosis. This study shows the biological potential of Piper imperiale extracts and gives way to bio-guided studies with well-defined biological activities.

  12. The strongest spectral lines of stable elements with other interfering elements in compiled and plotted version

    International Nuclear Information System (INIS)

    Bauer, M.; Weitkamp, C.

    1977-01-01

    The strongest spectra lines of the 85 stable chemical elements have been compiled and plotted along with lines from other elements that may interfere in applications like spectroscopic multielement analysis. For each line a wavelength range of +- 0.25 A.U. around the line of interest has been considered. The tables contain the wavelength, intensity and assignment to an ionization state of the emitting atom, the plots visualize the lines with a doppler broadening corresponding to 8,000 K. (orig.) [de

  13. Pitfall of the Strongest Cells in Static Random Access Memory Physical Unclonable Functions

    Directory of Open Access Journals (Sweden)

    Mingyang Gong

    2018-06-01

    Full Text Available Static Random Access Memory (SRAM Physical Unclonable Functions (PUFs are some of the most popular PUFs that provide a highly-secured solution for secret key storage. Given that PUF responses are noisy, the key reconstruction must use error correcting code (ECC to reduce the noise. Repetition code is widely used in resource constrained systems as it is concise and lightweight, however, research has shown that repetition codes can lead to information leakage. In this paper we found that the strongest cell distribution in a SRAM array may leak information of the responses of SRAM PUF when the repetition code is directly applied. Experimentally, on an ASIC platform with the HHGRACE 0.13 μm process, we recovered 8.3% of the measured response using the strongest cells revealed by the helper data, and we finally obtained a clone response 79% similar to weak response using the public helper data. We therefore propose Error Resistant Fuzzy Extractor (ERFE, a 4-bit error tolerant fuzzy extractor, that extracts the value of the sum of the responses as a unique key and reduces the failure rate to 1.8 × 10−8 with 256 bit entropy.

  14. Muscle quality and relative adiposity are the strongest predictors of lower-extremity physical function in older women.

    Science.gov (United States)

    Straight, Chad R; Brady, Anne O; Evans, Ellen M

    2015-01-01

    The aim of this study was to examine the relative contributions of physical activity, adiposity, lean mass and muscle quality to lower-extremity physical function (LEPF) in older women. Cross-sectional analysis at a university research laboratory. Community-dwelling older women (n=96, 73.9 ± 5.6 years, BMI=26.5 ± 4.7 kg/m(2)) were assessed for body composition via dual-energy X-ray absorptiometry, leg extension power using the Nottingham power rig, muscle quality (W/kg) as the ratio of leg extension power (W) to lower-body mineral free lean mass (kg) and moderate-intensity physical activity via questionnaire. A composite measure of LEPF was calculated by summing Z-scores of the 6-min walk, 8-foot up-and-go and 30-s chair stand tests. Muscle quality and physical activity were associated with all measures of LEPF (all p0.05). Hierarchical linear regression analyses revealed that muscle quality (standardized β=0.47, pquality and relative adiposity are the strongest independent predictors of LEPF in older women. These findings suggest that maintaining muscle quality, especially relative to adiposity, may be a critical target for interventions to prevent declines in physical function in older women. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Alcohol abuse as the strongest risk factor for violent offending in patients with paranoid schizophrenia.

    Science.gov (United States)

    Kudumija Slijepcevic, Marija; Jukic, Vlado; Novalic, Darko; Zarkovic-Palijan, Tija; Milosevic, Milan; Rosenzweig, Ivana

    2014-04-01

    To determine predictive risk factors for violent offending in patients with paranoid schizophrenia in Croatia. The cross-sectional study including male in-patients with paranoid schizophrenia with (N=104) and without (N=102) history of physical violence and violent offending was conducted simultaneously in several hospitals in Croatia during one-year period (2010-2011). Data on their sociodemographic characteristics, duration of untreated illness phase (DUP), alcohol abuse, suicidal behavior, personality features, and insight into illness were collected and compared between groups. Binary logistic regression model was used to determine the predictors of violent offending. Predictors of violent offending were older age, DUP before first contact with psychiatric services, and alcohol abuse. Regression model showed that the strongest positive predictive factor was harmful alcohol use, as determined by AUDIT test (odds ratio 37.01; 95% confidence interval 5.20-263.24). Psychopathy, emotional stability, and conscientiousness were significant positive predictive factors, while extroversion, pleasantness, and intellect were significant negative predictive factors for violent offending. This study found an association between alcohol abuse and the risk for violent offending in paranoid schizophrenia. We hope that this finding will help improve public and mental health prevention strategies in this vulnerable patient group.

  16. GAMMA BAND PLASTICITY IN SENSORY CORTEX IS A SIGNATURE OF THE STRONGEST MEMORY RATHER THAN MEMORY OF THE TRAINING STIMULUS

    Science.gov (United States)

    Weinberger, Norman M.; Miasnikov, Alexandre A.; Bieszczad, Kasia M.; Chen, Jemmy C.

    2013-01-01

    Gamma oscillations (~30–120 Hz) are considered to be a reflection of coordinated neuronal activity, linked to processes underlying synaptic integration and plasticity. Increases in gamma power within the cerebral cortex have been found during many cognitive processes such as attention, learning, memory and problem solving in both humans and animals. However, the specificity of gamma to the detailed contents of memory remains largely unknown. We investigated the relationship between learning-induced increased gamma power in the primary auditory cortex (A1) and the strength of memory for acoustic frequency. Adult male rats (n = 16) received three days (200 trials each) of pairing a tone (3.66 kHz) with stimulation of the nucleus basalis, which implanted a memory for acoustic frequency as assessed by associatively-induced disruption of ongoing behavior, viz., respiration. Post-training frequency generalization gradients (FGGs) revealed peaks at non-CS frequencies in 11/16 cases, likely reflecting normal variation in pre-training acoustic experiences. A stronger relationship was found between increased gamma power and the frequency with the strongest memory (peak of the difference between individual post- and pre-training FGGs) vs. behavioral responses to the CS training frequency. No such relationship was found for the theta/alpha band (4–15 Hz). These findings indicate that the strength of specific increased neuronal synchronization within primary sensory cortical fields can determine the specific contents of memory. PMID:23669065

  17. Gamma band plasticity in sensory cortex is a signature of the strongest memory rather than memory of the training stimulus.

    Science.gov (United States)

    Weinberger, Norman M; Miasnikov, Alexandre A; Bieszczad, Kasia M; Chen, Jemmy C

    2013-09-01

    Gamma oscillations (∼30-120Hz) are considered to be a reflection of coordinated neuronal activity, linked to processes underlying synaptic integration and plasticity. Increases in gamma power within the cerebral cortex have been found during many cognitive processes such as attention, learning, memory and problem solving in both humans and animals. However, the specificity of gamma to the detailed contents of memory remains largely unknown. We investigated the relationship between learning-induced increased gamma power in the primary auditory cortex (A1) and the strength of memory for acoustic frequency. Adult male rats (n=16) received three days (200 trials each) of pairing a tone (3.66 kHz) with stimulation of the nucleus basalis, which implanted a memory for acoustic frequency as assessed by associatively-induced disruption of ongoing behavior, viz., respiration. Post-training frequency generalization gradients (FGGs) revealed peaks at non-CS frequencies in 11/16 cases, likely reflecting normal variation in pre-training acoustic experiences. A stronger relationship was found between increased gamma power and the frequency with the strongest memory (peak of the difference between individual post- and pre-training FGGs) vs. behavioral responses to the CS training frequency. No such relationship was found for the theta/alpha band (4-15 Hz). These findings indicate that the strength of specific increased neuronal synchronization within primary sensory cortical fields can determine the specific contents of memory. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. The strongest magnetic barrier in the DIII-D tokamak and comparison with the ASDEX UG

    Science.gov (United States)

    Ali, Halima; Punjabi, Alkesh

    2013-05-01

    (2010)] based on continued fraction decomposition of the rotational transform labeling the barriers for selecting and identifying the strongest noble irrational barrier is used. The results are compared and contrasted with our previous results on the ASDEX UG. About six times stronger a barrier can be built in the DIII-D than in the ASDEX UG. High magnetic shear near the separatrix in the DIII-D is inferred as the possible cause of this. Implications of this for the DIII-D and the International Thermonuclear Experimental Reactor (ITER) are discussed.

  19. Education is the strongest socio-economic predictor of smoking in pregnancy.

    Science.gov (United States)

    Härkönen, Juho; Lindberg, Matti; Karlsson, Linnea; Karlsson, Hasse; Scheinin, Noora M

    2018-06-01

    To investigate socio-economic disparities in smoking in pregnancy (SIP) by the mother's education, occupational class and current economic conditions. Cross-sectional analysis with linked survey and register data. South-western Finland. A total of 2667 pregnant women [70% of the original sample (n = 3808)] from FinnBrain, a prospective pregnancy cohort study. The outcome was smoking during the first pregnancy trimester, measured from the Finnish Medical Birth Register. Education and occupational class were linked from population registers. Income support recipiency and subjective economic wellbeing were questionnaire-based measures of current economic conditions. These were adjusted for age, partnership status, residential area type, parental separation, parity, childhood socio-economic background, childhood adversities (the Trauma and Distressing Events During Childhood scale) and antenatal stress (Edinburgh Postnatal Depression Scale). Logistic regressions and attributable fractions (AF) were estimated. Mother's education was the strongest socio-economic predictor of SIP. Compared with university education, adjusted odds ratios (aORs) of SIP were: 2.2 [95% confidence interval (CI) = 1.2-3.9; P = 0.011] for tertiary vocational education, 4.4 (95% CI = 2.1-9.0; P < 0.001) for combined general and vocational secondary education, 2.9 (95% CI = 1.4-6.1; P = 0.006) for general secondary education, 9.5 (95% CI 5.0-18.2; P < 0.001) for vocational secondary education and 14.4 (95% CI = 6.3-33.0; P < 0.001) for compulsory schooling. The total AF of education was 0.5. Adjusted for the other variables, occupational class and subjective economic wellbeing did not predict SIP. Income support recipiency was associated positively with SIP (aOR = 1.8; 95% CI = 1.1-3.1; P = 0.022). Antenatal stress predicted SIP (aOR = 2.0; 95% CI = 1.4-2.8; P < 0.001), but did not attenuate its socio-economic disparities. In Finland, socio-economic disparities in

  20. 2-(Substituted phenyl-3,4-dihydroisoquinolin-2-iums as Novel Antifungal Lead Compounds: Biological Evaluation and Structure-Activity Relationships

    Directory of Open Access Journals (Sweden)

    Xin-Juan Yang

    2013-08-01

    Full Text Available The title compounds are a class of structurally simple analogues of quaternary benzo[c]phenanthridine alkaloids (QBAs. In order to develop novel QBA-like antifungal drugs, in this study, 24 of the title compounds with various substituents on the N-phenyl ring were evaluated for bioactivity against seven phytopathogenic fungi using the mycelial growth rate method and their SAR discussed. Almost all the compounds showed definite activities in vitro against each of the test fungi at 50 μg/mL and a broad antifungal spectrum. In most cases, the mono-halogenated compounds 2–12 exhibited excellent activities superior to the QBAs sanguinarine and chelerythrine. Compound 8 possessed the strongest activities on each of the fungi with EC50 values of 8.88–19.88 µg/mL and a significant concentration-dependent relationship. The SAR is as follows: the N-phenyl group is a high sensitive structural moiety for the activity and the characteristics and position of substituents intensively influence the activity. Generally, electron-withdrawing substituents remarkably enhance the activity while electron-donating substituents cause a decrease of the activity. In most cases, ortha- and para-halogenated isomers were more active than the corresponding m-halogenated isomers. Thus, the title compounds emerged as promising lead compounds for the development of novel biomimetic antifungal agrochemicals. Compounds 8 and 2 should have great potential as new broad spectrum antifungal agents for plant protection.

  1. Pulsar discoveries by volunteer distributed computing and the strongest continuous gravitational wave signal

    Science.gov (United States)

    Knispel, Benjamin

    2011-07-01

    Neutron stars are the endpoints of stellar evolution and one of the most compact forms of matter in the universe. They can be observed as radio pulsars and are promising sources for the emission of continuous gravitational waves. Discovering new radio pulsars in tight binary orbits offers the opportunity to conduct very high precision tests of General Relativity and to further our understanding of neutron star structure and matter at super-nuclear densities. The direct detection of gravitational waves would validate Einstein's theory of Relativity and open a new window to the universe by offering a novel astronomical tool. This thesis addresses both of these scientific fields: the first fully coherent search for radio pulsars in tight, circular orbits has been planned, set up and conducted in the course of this thesis. Two unusual radio pulsars, one of them in a binary system, have been discovered. The other half of this thesis is concerned with the simulation of the Galactic neutron star population to predict their emission of continuous gravitational waves. First realistic statistical upper limits on the strongest continuous gravitational-wave signal and detection predictions for realistic all-sky blind searches have been obtained. The data from a large-scale pulsar survey with the 305-m Arecibo radio telescope were searched for signals from radio pulsars in binary orbits. The massive amount of computational work was done on hundreds of thousands of computers volunteered by members of the general public through the distributed computing project Einstein@Home. The newly developed analysis pipeline searched for pulsar spin frequencies below 250 Hz and for orbital periods as short as 11 min. The structure of the search pipeline consisting of data preparation, data analysis, result post-processing, and set-up of the pipeline components is presented in detail. The first radio pulsar, discovered with this search, PSR J2007+2722, is an isolated radio pulsar, likely from

  2. Where was ENSO strongest?

    Science.gov (United States)

    Cane, M. A.; Chen, D.; Kaplan, A.

    2008-12-01

    Mark A. Cane, Dake Chen, Alexey Kaplan The description of this session begins: "Historical SST records suggest that for the past three decades, ENSO has been anomalously strong" and goes on to ask why. In this talk we dispute this interpretation of the historical record from within the historical record. In particular, we suggest that the most "anomalously strong" period in the historical ENSO record is the late nineteenth century. This claim requires a discussion of how we measure "ENSO strength". We also speculate on possible reasons for the strength of ENSO in this earlier period. Finally, we consult the models, and in reiteration of the collective conclusion of all speakers at this session, find that the riddles the models provide are inelegant and disobliging, lacking the cryptic wisdom of the classical oracles.

  3. Correlation between activation of PPAR¿ and resistin downregulation in a mouse adipocyte cell line by a series of thiazolidinediones.

    NARCIS (Netherlands)

    Sotiriou, A.; Blaauw, R.H.; Meijer, C.; Gijsbers, L.H.; Burg, van der B.; Vervoort, J.; Rietjens, I.M.C.M.

    2013-01-01

    The present study shows significant correlations between the EC50 for PPAR¿ activation in a reporter gene cell line and resistin downregulation in mouse adipocytes, and between the IC50 for resistin downregulation and the already published minimum effective dose for antihyperglycemic activity in a

  4. Atividade de três drogas antivirais sobre os herpesvírus bovino tipos 1, 2 e 5 em cultivo celular Activity of three antiviral drugs against bovine herpesviruses 1, 2 and 5 in cell culture

    Directory of Open Access Journals (Sweden)

    Renata Dezengrini

    2010-10-01

    Full Text Available A atividade de três fármacos antivirais (Aciclovir [ACV], Ganciclovir [GCV] e Foscarnet [PFA] foi testada in vitro frente aos herpesvírus bovino tipos 1 (BoHV-1, 2 (BoHV-2 e 5 (BoHV-5. Para isso, utilizou-se o teste de reducao de placas virais em cultivo celular, testando-se diferentes concentracoes dos farmacos frente a 100 doses infectantes para 50% dos cultivos celulares (DICC50 dos respectivos virus. Pelo teste de MTT (3-(4,5-Dimethylthiazol- 2-yl-2,5-diphenyltetrazolium bromide, verificou-se que concentracoes inferiores a 200ƒÊg/mL dos tres antivirais resultaram em indices de viabilidade de celulas MDBK e Hep2 superiores a 80%. Com base na concentracao citotoxica para 50% das celulas (CC50 e na concentracao dos farmacos efetiva para inibir em 50% o numero de placas virais (EC50, calculou-se o indice de seletividade (IS dos antivirais para os tres herpesvirus. Assim, o ACV demonstrou ser moderadamente ativo frente ao BoHV-1 (EC50: 112,9ƒÊg/mL e IS: 4,5, ao BoHV-2 (EC50: 114,2 ƒÊg/mL e IS: 4,5 e BoHV-5 (EC50: 96,9ƒÊg/mL e IS: 5,3. O GCV apresentou atividade moderada frente ao BoHV-2 (EC50: 33,5ƒÊg/mL e IS: 16,6 e, em menor grau, contra o BoHV-5 (EC50: 123,2ƒÊg/mL e IS: 4,5, sendo ineficaz frente ao BoHV-1 (EC50: 335,8ƒÊg/mL e IS: 1,7. O PFA apresentou atividade antiviral mais pronunciada, sendo o unico farmaco que, na concentracao de 100ƒÊg/mL, inibiu completamente a producao de placas pelos tres virus testados. O PFA foi o mais efetivo in vitro frente ao BoHV-1 (EC50: 29,5ƒÊg/mL e IS: 42,2, ao BoHV-2 (EC50: 45,2ƒÊg/mL e IS: 27,6 e ao BoHV-5 (EC50: 7,8ƒÊg/mL e IS: 160,6. Portanto, os resultados obtidos indicam que o PFA pode se constituir em um candidato para terapia experimental de infeccoes pelos herpesvirus de bovinos in vivo.The activity of three anti-herpetic drugs (Acyclovir [ACV], Gancyclovir [GCV] and Foscarnet [PFA] was tested against bovine herpesvirus 1 (BoHV-1, 2 (BoHV-2 and 5 (BoHV-5 in vitro using the

  5. The orphan G protein-coupled receptor GPR139 is activated by the peptides

    DEFF Research Database (Denmark)

    Jensen, Anne Cathrine Nøhr; Shehata, Mohamed A; Hauser, Alexander S

    2017-01-01

    GPR139 is an orphan G protein-coupled receptor that is expressed primarily in the brain. Not much is known regarding the function of GPR139. Recently we have shown that GPR139 is activated by the amino acids l-tryptophan and l-phenylalanine (EC50 values of 220 μM and 320 μM, respectively), as well...

  6. Mechanism of action of a novel human ether-a-go-go-related gene channel activator

    DEFF Research Database (Denmark)

    Casis, Oscar; Olesen, Søren-Peter; Sanguinetti, Michael C

    2005-01-01

    depolarizations, NS1643 enhanced the magnitude of wild-type hERG current in a concentration- and voltage-dependent manner with an EC(50) of 10.4 microM at -10 mV. The fully activated current-voltage relationship revealed that the drug increased outward but not inward currents, consistent with altered inactivation...

  7. Passive dosing of pyrethroid insecticides to Daphnia magna: Expressing excess toxicity by chemical activity

    DEFF Research Database (Denmark)

    Nørgaard Schmidt, Stine; Gan, Jay; Kretschmann, A. C.

    2015-01-01

    ) Effective chemical activities resulting in 50% immobilisation (Ea50) will be estimated from pyrethroid EC50 values via the correlation of sub-cooled liquid solubility (S L, [mmol/L], representing a=1) and octanol to water partitioning ratios (Kow), (3) The excess toxicity observed for pyrethroids...

  8. Metal ion site engineering indicates a global toggle switch model for seven-transmembrane receptor activation

    DEFF Research Database (Denmark)

    Elling, Christian E; Frimurer, Thomas M; Gerlach, Lars-Ole

    2006-01-01

    for monoamine binding in TM-III, was used as the starting point to engineer activating metal ion sites between the extracellular segments of the beta2-adrenergic receptor. Cu(II) and Zn(II) alone and in complex with aromatic chelators acted as potent (EC50 decreased to 0.5 microm) and efficacious agonists...

  9. Do nonphysical punishments reduce antisocial behavior more than spanking? a comparison using the strongest previous causal evidence against spanking

    Directory of Open Access Journals (Sweden)

    Cox Ronald B

    2010-02-01

    Full Text Available Abstract Background The strongest causal evidence that customary spanking increases antisocial behavior is based on prospective studies that control statistically for initial antisocial differences. None of those studies have investigated alternative disciplinary tactics that parents could use instead of spanking, however. Further, the small effects in those studies could be artifactual due to residual confounding, reflecting child effects on the frequency of all disciplinary tactics. This study re-analyzes the strongest causal evidence against customary spanking and uses these same methods to determine whether alternative disciplinary tactics are more effective in reducing antisocial behavior. Methods This study re-analyzed a study by Straus et al.1 on spanking and antisocial behavior using a sample of 785 children who were 6 to 9 years old in the 1988 cohort of the American National Longitudinal Survey of Youth. The comprehensiveness and reliability of the covariate measure of initial antisocial behavior were varied to test for residual confounding. All analyses were repeated for grounding, privilege removal, and sending children to their room, and for psychotherapy. To account for covarying use of disciplinary tactics, the analyses were redone first for the 73% who had reported using at least one discipline tactic and second by controlling for usage of other disciplinary tactics and psychotherapy. Results The apparently adverse effect of spanking on antisocial behavior was replicated using the original trichotomous covariate for initial antisocial behavior. A similar pattern of adverse effects was shown for grounding and psychotherapy and partially for the other two disciplinary tactics. All of these effects became non-significant after controlling for latent comprehensive measures of externalizing behavior problems. Conclusions These results are consistent with residual confounding, a statistical artifact that makes all corrective actions by

  10. In Vitro Studies on Phytochemical Content, Antioxidant, Anticancer, Immunomodulatory, and Antigenotoxic Activities of Lemon, Grapefruit, and Mandarin Citrus Peels.

    Science.gov (United States)

    Diab, Kawthar Ae

    2016-01-01

    In recent years, there has been considerable research on recycling of agroindustrial waste for production of bioactive compounds. The food processing industry produces large amounts of citrus peels that may be an inexpensive source of useful agents. The present work aimed to explore the phytochemical content, antioxidant, anticancer, antiproliferation, and antigenotxic activities of lemon, grapefruit, and mandarin peels. Peels were extracted using 98% ethanol and the three crude extracts were assessed for their total polyphenol content (TPC), total flavonoid content (TFC), and antioxidant activity using DPPH (1, 1diphenyl2picrylhydrazyl). Their cytotoxic and mitogenic proliferation activities were also studied in human leukemia HL60 cells and mouse splenocytes by CCK8 assay. In addition, genotoxic/ antigenotoxic activity was explored in mouse splenocytes using chromosomal aberrations (CAs) assay. Lemon peels had the highest of TPC followed by grapefruit and mandarin. In contrast, mandarin peels contained the highest of TFC followed by lemon and grapefruit peels. Among the extracts, lemon peel possessed the strongest antioxidant activity as indicated by the highest DPPH radical scavenging, the lowest effective concentration 50% (EC50= 42.97 ?g extract/ mL), and the highest Trolox equivalent antioxidant capacity (TEAC=0.157). Mandarin peel exhibited moderate cytotoxic activity (IC50 = 77.8 ?g/mL) against HL60 cells, whereas grapefruit and lemon peels were ineffective antileukemia. Further, citrus peels possessed immunostimulation activity via augmentation of proliferation of mouse splenocytes (Tlymphocytes). Citrus extracts exerted noncytotoxic, and antigenotoxic activities through remarkable reduction of CAs induced by cisplatin in mouse splenocytes for 24 h. The phytochemical constituents of the citrus peels may exert biological activities including anticancer, immunostimulation and antigenotoxic potential.

  11. Docking and Antiherpetic Activity of 2-Aminobenzo[de]-isoquinoline-1,3-diones

    Directory of Open Access Journals (Sweden)

    Rashad Al-Salahi

    2015-03-01

    Full Text Available As part of our search for new compounds having antiviral effects, the prepared 2-aminonaphthalimide series was examined for its activity against the herpes simplex viruses HSV-1 and HSV-2. This represents the first study of the antiviral effects of this class of compounds. The new series of 2-amino-1H-benzo[de]isoquinoline-1,3-diones was examined against HSV-1 and HSV-2 using a cytopathic effect inhibition assay. In terms of effective concentration (EC50, furaldehyde, thiophene aldehyde and allyl isothiocyanide derivatives 14‒16 showed potent activity against HSV-1 (EC50 = 19.6, 16.2 and 17.8 μg/mL, compared to acyclovir as a reference drug (EC50 = 1.8 μg/mL. Moreover, 14 and 15 were found to exhibit valuable activity against HSV-2. Many of the tested compounds demonstrated weak to moderate EC50 values relative to their inactive parent compound (2-amino-1H-benzo[de]isoquinoline-1,3-dione, while compounds 7, 9, 13, 14, 15, 16, 21 and 22 were the most active set of antiviral compounds throughout this study. The cytotoxicity (CC50, EC50, and the selectivity index (SI values were determined. In a molecular docking study, the ligand-receptor interactions of compounds 1–24 and their parent with the HSV-1 thymidine kinase active site were investigated using the Molegro Virtual Docker (MVD software. Based on the potent anti-HSV properties of the previous naphthalimide condensate products, further exploration of this series of 2-amino-1H-benzo[de]isoquinoline-1,3-diones is warranted.

  12. The 100 strongest radio point sources in the field of the Large Magellanic Cloud at 1.4 GHz

    Directory of Open Access Journals (Sweden)

    Payne J.L.

    2009-01-01

    Full Text Available We present the 100 strongest 1.4 GHz point sources from a new mosaic image in the direction of the Large Magellanic Cloud (LMC. The observations making up the mosaic were made using Australia Telescope Compact Array (ATCA over a ten year period and were combined with Parkes single dish data at 1.4 GHz to complete the image for short spacing. An initial list of co-identifications within 1000 at 0.843, 4.8 and 8.6 GHz consisted of 2682 sources. Elimination of extended objects and artifact noise allowed the creation of a refined list containing 1988 point sources. Most of these are presumed to be background objects seen through the LMC; a small portion may represent compact H ii regions, young SNRs and radio planetary nebulae. For the 1988 point sources we find a preliminary average spectral index (α of -0.53 and present a 1.4 GHz image showing source location in the direction of the LMC.

  13. The 100 Strongest Radio Point Sources in the Field of the Large Magellanic Cloud at 1.4 GHz

    Directory of Open Access Journals (Sweden)

    Payne, J. L.

    2009-06-01

    Full Text Available We present the 100 strongest 1.4~GHz point sources from a new mosaicimage in the direction of the Large Magellanic Cloud (LMC. The observationsmaking up the mosaic were made using Australia Telescope Compact Array (ATCAover a ten year period and were combined with Parkes single dish data at 1.4 GHz to complete the image for short spacing. An initial list of co-identifications within 10arcsec at 0.843, 4.8 and 8.6 GHz consisted of 2682 sources. Elimination of extended objects and artifact noise allowed the creation of a refined list containing 1988 point sources. Most of these are presumed to be background objects seen through the LMC; a small portion may represent compact HII regions, young SNRs and radio planetary nebulae. For the 1988 point sources we find a preliminary average spectral index ($alpha$ of -0.53 and present a 1.4 GHz image showing source locationin the direction of the LMC.

  14. Perception and the strongest sensory memory trace of multi-stable displays both form shortly after the stimulus onset.

    Science.gov (United States)

    Pastukhov, Alexander

    2016-02-01

    We investigated the relation between perception and sensory memory of multi-stable structure-from-motion displays. The latter is an implicit visual memory that reflects a recent history of perceptual dominance and influences only the initial perception of multi-stable displays. First, we established the earliest time point when the direction of an illusory rotation can be reversed after the display onset (29-114 ms). Because our display manipulation did not bias perception towards a specific direction of illusory rotation but only signaled the change in motion, this means that the perceptual dominance was established no later than 29-114 ms after the stimulus onset. Second, we used orientation-selectivity of sensory memory to establish which display orientation produced the strongest memory trace and when this orientation was presented during the preceding prime interval (80-140 ms). Surprisingly, both estimates point towards the time interval immediately after the display onset, indicating that both perception and sensory memory form at approximately the same time. This suggests a tighter integration between perception and sensory memory than previously thought, warrants a reconsideration of its role in visual perception, and indicates that sensory memory could be a unique behavioral correlate of the earlier perceptual inference that can be studied post hoc.

  15. Evidence for the strongest version of the 4d a-theorem via a-maximization along RG flows

    International Nuclear Information System (INIS)

    Barnes, Edwin; Intriligator, Ken; Wecht, Brian; Wright, Jason

    2004-01-01

    In earlier work, we (KI and BW) gave a two line 'almost proof' (for supersymmetric RG flows) of the weakest form of the conjectured 4d a-theorem, that aIRaUV, using our result that the exact superconformal R-symmetry of 4d SCFTs maximizes a=3TrR3-TrR. The proof was incomplete because of two identified loopholes: theories with accidental symmetries, and the fact that it is only a local maximum of a. Here we discuss and extend a proposal of Kutasov (which helps close the latter loophole) in which a-maximization is generalized away from the endpoints of the RG flow, with Lagrange multipliers that are conjectured to be identified with the running coupling constants. a-maximization then yields a monotonically decreasing 'a-function' along the RG flow to the IR. As we discuss, this proposal in fact suggests the strongest version of the a-theorem: that 4d RG flows are gradient flows of an a-function, with positive-definite metric. In the perturbative limit, the RG flow metric thus obtained is shown to agree precisely with that found by very different computations by Osborn and collaborators. As examples, we discuss a new class of 4d SCFTs, along with their dual descriptions and IR phases, obtained from SQCD by coupling some of the flavors to added singlets

  16. Seasonal influenza vaccination is the strongest correlate of cross-reactive antibody responses in migratory bird handlers.

    Science.gov (United States)

    Oshansky, Christine M; Wong, Sook-San; Jeevan, Trushar; Smallwood, Heather S; Webby, Richard J; Shafir, Shira C; Thomas, Paul G

    2014-12-09

    Avian species are reservoirs of influenza A viruses and could harbor viruses with significant pandemic potential. We examined the antibody and cellular immune responses to influenza A viruses in field or laboratory workers with a spectrum of occupational exposure to avian species for evidence of zoonotic infections. We measured the seroprevalence and T cell responses among 95 individuals with various types and degrees of prior field or laboratory occupational exposure to wild North American avian species using whole blood samples collected in 2010. Plasma samples were tested using endpoint enzyme-linked immunosorbent assay (ELISA) and hemagglutination (HA) inhibition (HAI) assays to subtypes H3, H4, H5, H6, H7, H8, and H12 proteins. Detectable antibodies were found against influenza HA antigens in 77% of individuals, while 65% of individuals tested had measurable T cell responses (gamma interferon [IFN-γ] enzyme-linked immunosorbent spot assay [ELISPOT]) to multiple HA antigens of avian origin. To begin defining the observed antibody specificities, Spearman rank correlation analysis showed that ELISA responses, which measure both head- and stalk-binding antibodies, do not predict HAI reactivities, which measure primarily head-binding antibodies. This result suggests that ELISA titers can report cross-reactivity based on the levels of non-head-binding responses. However, the strongest positive correlate of HA-specific ELISA antibody titers was receipt of seasonal influenza virus vaccination. Occupational exposure was largely uncorrelated with serological measures, with the exception of individuals exposed to poultry, who had higher levels of H7-specific antibodies than non-poultry-exposed individuals. While the cohort had antibody and T cell reactivity to a broad range of influenza viruses, only occupational exposure to poultry was associated with a significant difference in antibody levels to a specific subtype (H7). There was no evidence that T cell assays

  17. In Vitro Antioxidant and Antiproliferative Activities of Novel Orange Peel Extract and It's Fractions on Leukemia HL-60 Cells.

    Science.gov (United States)

    Diab, Kawthar A E; Shafik, Reham Ezzat; Yasuda, Shin

    2015-01-01

    In the present work, novel orange peel was extracted with 100%EtOH (ethanol) and fractionated into four fractions namely F1, F2, F3, F4 which were eluted from paper chromatographs using 100%EtOH, 80%EtOH, 50%EtOH and pure water respectively. The crude extract and its four fractions were evaluated for their total polyphenol content (TPC), total flavonoid content (TFC) and radical scavenging activity using DPPH (1,1-diphenyl-2-picrylhydrazyl) assay. Their cytotoxic activity using WST assay and DNA damage by agarose gel electrophoresis were also evaluated in a human leukemia HL-60 cell line. The findings revealed that F4 had the highest TPC followed by crude extract, F2, F3 and F1. However, the crude extract had the highest TFC followed by F4, F3, F2, and F1. Depending on the values of EC50 and trolox equivalent antioxidant capacity, F4 possessed the strongest antioxidant activity while F1 and F2 displayed weak antioxidant activity. Further, incubation HL-60 cells with extract/fractions for 24h caused an inhibition of cell viability in a concentration- dependent manner. F3 and F4 exhibited a high antiproliferative activity with a narrow range of IC50 values (45.9 - 48.9 μg/ml). Crude extract exhibited the weakest antiproliferative activity with an IC50 value of 314.89 μg/ml. Analysis of DNA fragmentation displayed DNA degradation in the form of a smear-type pattern upon agarose gel after incubation of HL-60 cells with F3 and F4 for 6 h. Overall, F3 and F4 appear to be good sources of phytochemicals with antioxidant and potential anticancer activities.

  18. Hemoglobin to Hematocrit Ratio: The Strongest Predictor of Femoral Head Osteonecrosis in Children With Sickle Cell Disease.

    Science.gov (United States)

    Worrall, Douglas; Smith-Whitley, Kim; Wells, Lawrence

    2016-03-01

    Femoral head osteonecrosis (ON) secondary to sickle cell disease (SCD) often progresses to femoral head collapse, requiring total hip arthroplasty. However, this treatment has a limited durability and patients with SCD have higher rates of complications, requiring multiple revision operations. Identifying risk factors linked to ON in SCD can facilitate earlier precollapse diagnosis and surgical treatment aimed at preservation of the native hip joint. Fifty-nine children treated at our institution between January 2001 and April 2012 with SCD and ON, as diagnosed by magnetic resonance imaging or radiographic imaging, were compared with age-matched and sickle cell phenotype-matched (SS, SC, Sβ, Sβ) controls with no evidence of ON. Two sided t-tests assuming unequal variances determined statistically risk factors and threshold values were assigned to calculate odds ratios. Systolic blood pressure (P=1.2×10, OR=3.68), diastolic blood pressure (P=0.0084, OR=1.41), weight in the SCD-SS population (P=0.04, OR=1.85), and hemoglobin (Hb) in the SCD-SS population (P=0.036, OR=2.56) were elevated in cases. Curiously, dividing the Hb by the hematocrit to serve as a clinical proxy for the mean corpuscular Hb concentration (MCHC) produced an excellent predictor of ON (P=2.06×10, OR=5.17), which was especially pronounced in the SCD-SS subpopulation (P=2.28×10, OR=8.65). Among children with SCD, the overall prevalence of ON was 9% (59/658) and the phenotype with the highest prevalence of ON was Sβ thalassemia with an ON prevalence of 11.1%. There was no observed correlation between ON and height, body mass index, cholesterol, mean corpuscular volume, hematocrit, or glucocorticoid use. These data support a novel clinical marker, the MCHC proxy, as the strongest predictor of ON in children with SCD. High-risk children should receive hip magnetic resonance imaging to diagnose early ON and facilitate interventions focused on hip preservation, forestalling, or possibly preventing

  19. Identification of some chemical constituents of Indigofera hirsuta Linn. (Fabaceae) by HPLC-ESI-MS (TOF) and evaluation of the anti radical activity

    International Nuclear Information System (INIS)

    Moura, Adriana Candido da Silva; Vilegas, Wagner; Santos, Lourdes Campaner dos

    2011-01-01

    A rapid analytical approach, suitable to characterize the compounds present in the aqueous and methanol extracts prepared from the aerial parts of Indigofera hirsute, was developed. The method based on high-performance liquid chromatography coupled to mass spectrometry, electrospray positive ionization and detection by time of flight (HPLC-ESI-MS-TOF) identified, tryptophan, uracil, rutin, kempferol-3-Oβ - -D-glucopyranoside, gallic acid and methyl gallate. The antiradical activity of this extract was evaluated using DPPH assay, with gallic acid as antiradical pattern. The study revealed the antiradical activity of methyl galatte (EC 50 = 5 ± 0.3 μg mL -1 ) gallic acid (EC 50 = 5 ± 0.2 μg mL -1 ) and rutin (EC 50 = 21.6 ± 0.6 μg m L -1 ), isolated from methanol extract (EC 50 = 67.7 ± 0.9 μg mL -1 ), which showed strong antiradical activity. (author)

  20. Novel Phenolic Inhibitors of Small/Intermediate-Conductance Ca(2+)-Activated K(+) Channels, KCa3.1 and KCa2.3

    DEFF Research Database (Denmark)

    Olivan-Viguera, Aida; Valero, Marta Sofía; Murillo, María Divina

    2013-01-01

    -inflammatory drugs (NSAIDs), with known cytoprotective, anti-inflammatory, and/or cytostatic activities. METHODOLOGYPRINCIPAL FINDINGS: In electrophysiological experiments, we identified the natural phenols, caffeic acid (EC50 1.3 µM) and resveratrol (EC50 10 µM) as KCa3.1 inhibitors with moderate potency....... The phenols, vanillic acid, gallic acid, and hydroxytyrosol had weak or no blocking effects. Out of the NSAIDs, flufenamic acid was moderately potent (EC50 1.6 µM), followed by mesalamine (EC50≥10 µM). The synthetic fluoro-trivanillic ester, 13b ([3,5-bis[(3-fluoro-4-hydroxy-benzoyl)oxymethyl]phenyl]methyl 3.......3 activation. CONCLUSIONSSIGNIFICANCE: We identified the natural phenols, caffeic acid and resveratrol, the NSAID, flufenamic acid, and the polyphenol 13b as novel KCa3.1 inhibitors. The high potency of 13b with pan-activity on KCa3.1/KCa2 channels makes 13b a new pharmacological tool to manipulate...

  1. The 9.2 ka event in Asian summer monsoon area: the strongest millennial scale collapse of the monsoon during the Holocene

    Science.gov (United States)

    Zhang, Wenchao; Yan, Hong; Dodson, John; Cheng, Peng; Liu, Chengcheng; Li, Jianyong; Lu, Fengyan; Zhou, Weijian; An, Zhisheng

    2018-04-01

    Numerous Holocene paleo-proxy records exhibit a series of centennial-millennial scale rapid climatic events. Unlike the widely acknowledged 8.2 ka climate anomaly, the likelihood of a significant climate excursion at around 9.2 cal ka BP, which has been notably recognized in some studies, remains to be fully clarified in terms of its magnitude and intensity, as well as its characteristics and spatial distributions in a range of paleoclimatic records. In this study, a peat sediment profile from the Dajiuhu Basin in central China was collected with several geochemical proxies and a pollen analysis carried out to help improve understanding of the climate changes around 9.2 cal ka BP. The results show that the peat development was interrupted abruptly at around 9.2 cal ka BP, when the chemical weathering strength decreased and the tree-pollen declined. This suggests that a strong drier regional climatic event occurred at around 9.2 cal ka BP in central China, which was, in turn, probably connected to the rapid 9.2 ka climate event co-developing worldwide. In addition, based on the synthesis of our peat records and the other Holocene hydrological records from Asian summer monsoon (ASM) region, we further found that the 9.2 ka event probably constituted the strongest abrupt collapse of the Asian monsoon system during the full Holocene interval. The correlations between ASM and the atmospheric 14C production rate, the North Atlantic drift ice records and Greenland temperature indicated that the weakened ASM event at around 9.2 cal ka BP could be interpreted by the co-influence of external and internal factors, related to the changes of the solar activity and the Atlantic Meridional Overturning Circulation (AMOC).

  2. Heart and/or soul : reality and fiction in the association between the two strongest contributors to the global burden of disease - ischemic heart disease and depression

    NARCIS (Netherlands)

    de Jonge, Peter

    Depression and heart disease are the strongest contributors to the global burden of disease and are often intertwined: depression is a risk factor for heart disease and vice versa. Moreover, depression in patients with established heart disease is associated with cardiovascular disease progression.

  3. Total phenolics and antioxidant activity of five medicinal plant

    International Nuclear Information System (INIS)

    Sousa, Cleyton Marcos de M.; Silva, Hilris Rocha e; Vieira-Junior, Gerardo Magela; Ayres, Mariane Cruz C.; Costa, Charllyton Luis S. da; Araajo, Delton Servulo; Cavalcante, Luis Carlos D.; Barros, Elcio Daniel S.; Araujo, Paulo Breitner de M.; Brandao, Marcela S.; Chaves, Mariana H.

    2007-01-01

    This paper describes total phenolics content and antioxidant activity in the ethanolic extract of leaves, bark and roots of five medicinal plants: Terminalia brasiliensis Camb., Terminalia fagifolia Mart. and Zucc., Copernicia cerifera (Miller) H.E. Moore, Cenostigma macrophyllum Tul. var. acuminata Teles Freire and Qualea grandiflora Mart. The total phenolics content of the plant extracts, determined by the Folin-Ciocalteu method, varied from 250.0 ±8,2 to 763,63 ±13.03 mg of gallic acid equivalent/g dry EtOH extract. The antioxidant activity of extracts was evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay system. Extract of bark from T. brasiliensis, the most active, with an EC 50 value of 27.59 ± 0.82 μg/mL, was comparable to rutin (EC 50 = 27.80 ± 1.38) and gallic acid (EC 50 = 24.27 ± 0.31), used as positive controls. The relationship between total phenolic content and antioxidant activity was positive and significant for T. brasiliensis, C. macrophyllum and C. cerifera. (author)

  4. "My Voice Is Definitely Strongest in Online Communities": Students Using Social Media for Queer and Disability Identity-Making

    Science.gov (United States)

    Miller, Ryan A.

    2017-01-01

    In this qualitative study I explored the social media activities of 25 lesbian, gay, bisexual, transgender, and queer students with disabilities at a research-intensive university. Using a framework of identity-making that accounts for students' reflections, narrations, and actions, I detail students' experiences exploring queer/ disability…

  5. Nematicidal activity of furanocoumarins from parsley against Meloidogyne spp.

    Science.gov (United States)

    Caboni, Pierluigi; Saba, Marco; Oplos, Chrisostomos; Aissani, Nadhem; Maxia, Andrea; Menkissoglu-Spiroudi, Urania; Casu, Laura; Ntalli, Nikoletta

    2015-08-01

    This report describes activity against Meloidogyne spp. and chemical characterisation of the essential oil and methanol extract of Petroselinum crispum aerial parts. The study was based on the hypothesis that P. crispum could be used as an intercrop and soil amendment in tomato culture for nematode control. The methanol extract and the essential oil exhibited significant nematicidal activity against M. incognita, M. hapla and M. arenaria, the first being the most sensitive species, with EC50 /72 h values of 140 ± 15 and 795 ± 125 mg L(-1) for the extract and oil respectively. The most abundant furanocoumarin compounds in the methanolic extract were xanthotoxin, psoralen, bergapten and oxypeucedanin; levels ranged from 1.77 to 46.04 mg kg(-1) wet weight. The EC50 /24 h values of xanthotoxol, psoralen and xanthotoxin against M. incognita were 68 ± 33, 147 ± 88 and 200 ± 21 mg L(-1) respectively. The addition of fresh parsley paste to soil reduced the number of M. incognita females and plant galls on tomato roots; EC50 values were 24.79 and 28.07 mg g(-1) respectively. Moreover, parsley paste enhanced tomato growth in a dose-response manner. Parsley exhibits promising nematicidal activity as an organic amendment and as a source of nematotoxic furanocoumarins. © 2014 Society of Chemical Industry.

  6. In vitro anthelmintic activity of active compounds of the fringed rue Ruta chalepensis against dairy ewe gastrointestinal nematodes.

    Science.gov (United States)

    Ortu, E; Sanna, G; Scala, A; Pulina, G; Caboni, P; Battacone, G

    2017-07-01

    Infections by gastrointestinal nematodes negatively affect small ruminant health and at the same time cause substantial economic losses worldwide. Because resistance to conventional anthelmintic compounds is growing, target studies evaluating the effectiveness of alternative ingredients of botanical origin on gastrointestinal nematodes are needed. In this study, we evaluated the in vitro anthelmintic activity of Ruta chalepensis L. extracts on the third-stage larvae of sheep gastrointestinal nematodes. A methanol extract showed the highest anthelmintic activity, with an EC50 = 0.10 ± 0.06 mg/ml after 96 h, while the essential oil had an EC50 = 1.45 ± 1.22 mg/ml after 48 h. Moreover, three secondary metabolites of the essential oil, i.e. 2-decanone, 2-nonanone and 2-undecanone, showed EC50 values of 0.07 ± 0.06, 0.25 ± 0.29 and 0.88 ± 0.73 mg/ml at 24 h, respectively. The present study indicated that the R. chalepensis methanol extract, the essential oil and its metabolites 2-decanone, 2-nonanone and 2-undecanone showed promising anthelmintic activity on gastrointestinal nematodes.

  7. Antiherpetic activity of a flavonoid fraction from Ocotea notata leaves

    Directory of Open Access Journals (Sweden)

    Rafael Garrett

    2012-01-01

    Full Text Available This study describes the isolation of a flavonoid fraction from leaves of Ocotea notata (Nees & Mart. Mez, Lauraceae, the identification of six major compounds (an A-type proanthocyanidin trimer [3], isoquercitrin [4], reynoutrin [5], miquelianin [6], quercitrin [7], afzelin [8] and four minor compounds (catechin [1], epicatechin [2], quercetin [9], kaempferol [10] present in the fraction and its activity against the Herpes simplex virus type 1 (HSV-1 and type 2 (HSV-2. The 50% effective concentrations values (EC50 calculated from the dose-response curve and the selectivity indices (SI against the virus were: EC50 35.8 µg/mL and SI 5.5 to HSV-1 and EC50 23.5 µg/mL and SI 8.5 to HSV-2. The flavonoid fraction was more active against HSV-2 than HSV-1. The mechanisms of antiviral action of the flavonoid fraction against the virus were also evaluated. The percentage inhibition (PI obtained for HSV-2 was higher than 90% in the following assays: virucidal, pre-treatment of cells, treatment of cells after viral adsorption and treatment of cells after viral penetration. For HSV-1, the flavonoid fraction had no effect in pre-treatment of cells and showed 60% of inhibition in virucidal assay.

  8. Antiherpetic activity of a flavonoid fraction from Ocotea notata leaves

    Directory of Open Access Journals (Sweden)

    Rafael Garrett

    2012-04-01

    Full Text Available This study describes the isolation of a flavonoid fraction from leaves of Ocotea notata (Nees & Mart. Mez, Lauraceae, the identification of six major compounds (an A-type proanthocyanidin trimer [3], isoquercitrin [4], reynoutrin [5], miquelianin [6], quercitrin [7], afzelin [8] and four minor compounds (catechin [1], epicatechin [2], quercetin [9], kaempferol [10] present in the fraction and its activity against the Herpes simplex virus type 1 (HSV-1 and type 2 (HSV-2. The 50% effective concentrations values (EC50 calculated from the dose-response curve and the selectivity indices (SI against the virus were: EC50 35.8 µg/mL and SI 5.5 to HSV-1 and EC50 23.5 µg/mL and SI 8.5 to HSV-2. The flavonoid fraction was more active against HSV-2 than HSV-1. The mechanisms of antiviral action of the flavonoid fraction against the virus were also evaluated. The percentage inhibition (PI obtained for HSV-2 was higher than 90% in the following assays: virucidal, pre-treatment of cells, treatment of cells after viral adsorption and treatment of cells after viral penetration. For HSV-1, the flavonoid fraction had no effect in pre-treatment of cells and showed 60% of inhibition in virucidal assay.

  9. Structure-Activity Relationships of Acyclic Selenopurine Nucleosides as Antiviral Agents

    Directory of Open Access Journals (Sweden)

    Pramod K. Sahu

    2017-07-01

    Full Text Available A series of acyclic selenopurine nucleosides 3a–f and 4a–g were synthesized based on the bioisosteric rationale between oxygen and selenium, and then evaluated for antiviral activity. Among the compounds tested, seleno-acyclovir (4a exhibited the most potent anti-herpes simplex virus (HSV-1 (EC50 = 1.47 µM and HSV-2 (EC50 = 6.34 µM activities without cytotoxicity up to 100 µM, while 2,6-diaminopurine derivatives 4e–g exhibited significant anti-human cytomegalovirus (HCMV activity, which is slightly more potent than the guanine derivative 4d, indicating that they might act as prodrugs of seleno-ganciclovir (4d.

  10. Activity of alkanediol alkanoates against pathogenic plant fungi Rhizoctonia solani and Sclerotium rolfsii.

    Science.gov (United States)

    Shukla, Paraj; Walia, Suresh; Ahluwalia, Vivek; Parmar, Balraj S; Nair, Muraleedharan G

    2012-09-01

    Thirty known dialkanoates of ethylene, propylene and diethylene glycols were synthesized by reacting the glycols with acyl chlorides and their structures confirmed by IR, NMR and mass spectral analyses. They exhibited significant antifungal activity against two phytopathogenic fungi Rhizoctonia solani Kuehn and Sclerotium rolfsii Sacc in a dose dependent manner. Propylene glycol dipentanoate was the most active against R. solani. followed by diethylene glycol dibutanoate and ethylene glycol dibutanoate. Against S. rolfsii ethylene glycol diheptanoate was found to be most active followed by diethylene glycol diisobutanoate As compared to the standard reference benomyl (EC50 5.16 microg/mL), the potential alkanediol dialkanoates showed EC50 in the range of 33 - 60 microg/mL.

  11. Evaluation of the antioxidant activity of extracts and flavonoids obtained from Bunium alpinum Waldst.

    Directory of Open Access Journals (Sweden)

    Lefahal Mostefa

    2017-03-01

    Full Text Available The aim of the present work was to evaluate the antioxidant activity of extracts and four flavonoids that had been isolated from the aerial parts of Bunium alpinum Waldst. et Kit. (Apiaceae and Tamarix gallica L. (Tamaricaceae. In this work, the four flavonoids were first extracted via various solvents, then purified through column chromatography (CC and thin layer chromatography (TLC. The four compounds were subsequently identified by spectroscopic methods, including: UV, mass spectrum 1H NMR and 13C NMR. The EtOAc extract of Bunium alpinum Waldst. et Kit yielded quercetin-3-O-β-glucoside (3’,4’,5,7-Tetrahydroxyflavone-3-β-D-glucopyranoside (1, while the EtOAc and n-BuOH extracts of Tamarix gallica L. afforded 3,5,3’-trihydroxy-7,4’-dimethoxyflavone (2, 3,5,7-trihydroxy-4’-methoxyflavone (3 and 5-hydroxy-3,7,4’-trimethoxyflavone (4. The antioxidant activity of the extracts and the flavonoids were then evaluated through DPPH free radical-scavenging assay. Of all studied extracts, the n-Butanol extract of Bunium alpinum (EC50 = 1.84 μg/ml showed the best antioxidant activity against (DPPH. In contrast, the isolates demonstrated varying degrees of antioxidant activity: compound (1 was the more active (EC50 = 0.28 μg/ml, followed by compound (3 and (2 (EC50 = 0.309μg/ml, EC50 = 0.406 μg/ml, respectively, compound (4 showed the lowest activity. All the isolated flavonoids exhibited antioxidant activity, but this was lower than the control (Trolox. In conclusion, due to the presence of flavonoids in their ariel parts, the studied plants could be natural sources of several important antioxidant agents

  12. N-ω-chloroacetyl-L-ornithine has in-vitro activity against cancer cell lines and in-vivo activity against ascitic and solid tumors.

    Science.gov (United States)

    Vargas-Ramírez, Alba L; Medina-Enríquez, Miriam M; Cordero-Rodríguez, Neira I; Ruiz-Cuello, Tatiana; Aguilar-Faisal, Leopoldo; Trujillo-Ferrara, José G; Alcántara-Farfán, Verónica; Rodríguez-Páez, Lorena

    2016-07-01

    N-ω-chloroacetyl-L-ornithine (NCAO) is an ornithine decarboxylase (ODC) inhibitor that is known to exert cytotoxic and antiproliferative effects on three neoplastic human cancer cell lines (HeLa, MCF-7, and HepG2). Here, we show that NCAO has antiproliferative activity in 13 cancer cell lines, of diverse tissue origin from human and mice, and in a mouse cancer model in vivo. All cell lines were sensitive to NCAO after 72 h of treatment (the EC50 ranged from 1 to 50.6 µmol/l). The Ca Ski cell line was the most sensitive (EC50=1.18±0.07 µmol/l) and MDA-MB-231 was the least sensitive (EC50=50.6±0.3 µmol/l). This ODC inhibitor showed selectivity for cancer cells, exerting almost no cytotoxic effect on the normal Vero cell line (EC50>1000 µmol/l). NCAO induced apoptosis and inhibited tumor cell migration in vitro. Furthermore, in vivo, this compound (at 50 and 100 mg/kg, daily intraperitoneal injection for 7 days) exerted potent antitumor activity against both solid and ascitic tumors in a mouse model using the myeloma (Ag8) cell line. At these same two doses, the toxicological evaluation showed that NCAO has no obvious systemic toxicity. The current results suggest that the antitumor activity is exerted by apoptosis related not only to a local but also a systemic cytotoxic effect exerted by NCAO on tumor cells. The applications for NCAO as an antitumor agent may be extensive; however, further studies are needed to ascertain the antitumor activity on other types of tumor in vivo and to determine the precise molecular mechanism of its activity.

  13. Remote population-based intervention for disruptive behavior at age four: study protocol for a randomized trial of Internet-assisted parent training (Strongest Families Finland-Canada)

    Science.gov (United States)

    2013-01-01

    Background Oppositional Defiant Disorder (ODD) is characterized by angry and noncompliant behaviour. It is the most common disruptive behaviour disorder (DBD), with prevalence estimates of 6-9% for preschoolers and is closely linked to several long-term difficulties, including disorders of conduct, mood, anxiety, impulse-control, and substance abuse. ODD in children is related to parental depression, family dysfunction, and impairments in parental work performance. Children displaying early DBDs exhibit more symptoms of greater severity, more frequent offences, and commit more serious crimes later in life. The goal of the Strongest Families™ Finland Canada (SFFC) Smart Website intervention research program is to develop and evaluate an affordable, accessible, effective secondary prevention parent training program for disruptive behaviour in preschoolers to prevent the negative sequelae of ODD. Strongest Families is an 11-session program with two booster sessions that focuses on teaching skills to: strengthen parent–child relationships; reinforce positive behaviour; reduce conflict; manage daily transitions; plan for potentially problematic situations; promote emotional regulation and pro-social behaviour and decrease antisocial behaviour. Methods/design This protocol paper describes an ongoing population-based randomized controlled trial (RCT) of high-risk 4 year-olds attending well-child clinics in Turku, Finland and environs to examine the effectiveness of the Strongest Families Smart Website intervention compared to an Education Control condition. Randomization consists of a 1:1 ratio for intervention versus the education group, stratified by the child’s sex. The participants randomized to the intervention group receive access to the Strongest Families Smart Website and weekly telephone coaching sessions. The participants randomized to the Education Control condition receive access to a static website with parenting tips. Children are followed using

  14. Remote population-based intervention for disruptive behavior at age four: study protocol for a randomized trial of Internet-assisted parent training (Strongest Families Finland-Canada).

    Science.gov (United States)

    McGrath, Patrick J; Sourander, Andre; Lingley-Pottie, Patricia; Ristkari, Terja; Cunningham, Charles; Huttunen, Jukka; Filbert, Katharine; Aromaa, Minna; Corkum, Penny; Hinkka-Yli-Salomäki, Susanna; Kinnunen, Malin; Lampi, Katja; Penttinen, Anne; Sinokki, Atte; Unruh, Anita; Vuorio, Jenni; Watters, Carolyn

    2013-10-21

    Oppositional Defiant Disorder (ODD) is characterized by angry and noncompliant behaviour. It is the most common disruptive behaviour disorder (DBD), with prevalence estimates of 6-9% for preschoolers and is closely linked to several long-term difficulties, including disorders of conduct, mood, anxiety, impulse-control, and substance abuse. ODD in children is related to parental depression, family dysfunction, and impairments in parental work performance. Children displaying early DBDs exhibit more symptoms of greater severity, more frequent offences, and commit more serious crimes later in life. The goal of the Strongest Families Finland Canada (SFFC) Smart Website intervention research program is to develop and evaluate an affordable, accessible, effective secondary prevention parent training program for disruptive behaviour in preschoolers to prevent the negative sequelae of ODD. Strongest Families is an 11-session program with two booster sessions that focuses on teaching skills to: strengthen parent-child relationships; reinforce positive behaviour; reduce conflict; manage daily transitions; plan for potentially problematic situations; promote emotional regulation and pro-social behaviour and decrease antisocial behaviour. This protocol paper describes an ongoing population-based randomized controlled trial (RCT) of high-risk 4 year-olds attending well-child clinics in Turku, Finland and environs to examine the effectiveness of the Strongest Families Smart Website intervention compared to an Education Control condition. Randomization consists of a 1:1 ratio for intervention versus the education group, stratified by the child's sex. The participants randomized to the intervention group receive access to the Strongest Families Smart Website and weekly telephone coaching sessions. The participants randomized to the Education Control condition receive access to a static website with parenting tips. Children are followed using parental and daycare teacher measures

  15. Synthesis, Antifungal Activity and QSAR of Some Novel Carboxylic Acid Amides

    Directory of Open Access Journals (Sweden)

    Shijie Du

    2015-03-01

    Full Text Available A series of novel aromatic carboxylic acid amides were synthesized and tested for their activities against six phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to good activity. Among them N-(2-(1H-indazol-1-ylphenyl-2-(trifluoromethylbenzamide (3c exhibited the highest antifungal activity against Pythium aphanidermatum (EC50 = 16.75 µg/mL and Rhizoctonia solani (EC50 = 19.19 µg/mL, compared to the reference compound boscalid with EC50 values of 10.68 and 14.47 µg/mL, respectively. Comparative molecular field analysis (CoMFA and comparative molecular similarity indices analysis (CoMSIA were employed to develop a three-dimensional quantitative structure-activity relationship model for the activity of the compounds. In the molecular docking, a fluorine atom and the carbonyl oxygen atom of 3c formed hydrogen bonds toward the hydroxyl hydrogens of TYR58 and TRP173.

  16. Ecotoxicological effects of copper and selenium combined pollution on soil enzyme activities in planted and unplanted soils.

    Science.gov (United States)

    Hu, Bin; Liang, Dongli; Liu, Juanjuan; Xie, Junyu

    2013-04-01

    The present study explored the joint effects of Cu and Se pollution mechanisms on soil enzymes to provide references for the phytoremediation of contaminated areas and agricultural environmental protection. Pot experiments and laboratory analyses were carried out to study the individual and combined influences of Cu and Se on soil enzyme activities. The activities of four soil enzymes (urease, catalase, alkaline phosphatase, and nitrate reductase) were chosen. All soil enzyme activities tested were inhibited by Cu and Se pollution, either individually or combined, in varying degrees, following the order nitrate reductase>urease>catalase>alkaline phosphatase. Growing plants stimulated soil enzyme activity in a similar trend compared with treatments without plants. The joint effects of Cu and Se on catalase activity showed synergism at low concentrations and antagonism at high concentrations, whereas the opposite was observed for urease activity. However, nitrate reductase activity showed synergism both with and without plant treatments. The half maximal effective concentration (EC50) of exchangeable fractions had a similar trend with the EC50 of total content and was lower than that of total content. The EC50 values of nitrate reductase and urease activities were significantly lower for both Se and Cu (p<0.05), which indicated that they were more sensitive than the other two enzymes. Copyright © 2013 SETAC.

  17. Isocyanides Derived from α,α-Disubstituted Amino Acids: Synthesis and Antifouling Activity Assessment.

    Science.gov (United States)

    Inoue, Yuki; Takashima, Shuhei; Nogata, Yasuyuki; Yoshimura, Erina; Chiba, Kazuhiro; Kitano, Yoshikazu

    2018-03-01

    Herein, we contribute to the development of environmentally friendly antifoulants by synthesizing eighteen isocyanides derived from α,α-disubstituted amino acids and evaluating their antifouling activity/toxicity against the cypris larvae of the Balanus amphitrite barnacle. Almost all isocyanides showed good antifouling activity without significant toxicity and exhibited EC 50 values of 0.07 - 7.30 μg/mL after 120-h exposure. The lowest EC 50 values were observed for valine-, methionine-, and phenylalanine-derived isocyanides, which achieved > 95% cypris larvae settlement inhibition at concentrations of less than 30 μg/mL without exhibiting significant toxicity. Thus, the prepared isocyanides should be useful for further research focused on the development of environmentally friendly antifouling agents. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

  18. Chemical Constituents and Antioxidant Activity of fresh leaves of psidium guajava cultivated in pakistan

    International Nuclear Information System (INIS)

    Begum, S.; Ali, S.N.; Tauseef, S.

    2014-01-01

    The in vitro antioxidant activities of the methanol extract of fresh leaves of Psidium guajava cultivated in Pakistan and its different fractions were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay. The methanol extract, main ethyl acetate fraction and its polar sub fraction showed high free radical scavenging activity with EC50 11.72, 11.72 and 46.8 micro g/mL respectively. The first two values are comparable with that of reference compound ascorbic acid (EC50 9.4 ?g/mL). The known antioxidants gallic acid (1), methyl ferulate (2) and methyl p-E-coumarate (3) were isolated from the ethyl acetate insoluble fraction. Their structures were identified by mass, 1H- and 13C-NMR spectroscopy. Compounds 2 and 3 are reported for the first time from the genus Psidium. (author)

  19. In vitro antiviral activity of aqueous extract of Phaleria macrocarpa fruit against herpes simplex virus type 1

    Science.gov (United States)

    Ismaeel, Mahmud Yusef Yusef; Dyari, Herryawan Ryadi Eziwar; Yaacob, Wan Ahmad; Ibrahim, Nazlina

    2018-04-01

    Phaleria macrocarpa fruits have been used as herbal medicine for several diseases. This study aims to determine the cytotoxicity and antiviral activity of aqueous extract of P. macrocarpa fruit (AEPMF). Phytochemical analysis showed the presence of steroids, tannins, flavones aglycones, saponins, terpenoids and alkaloids. AEPMF was found to contain protein with the concentration of 740 µg/mL. The cytotoxicity towards Vero cell was evaluated using MTT assay with 50% cytotoxic concentration (CC50) value of AEPMF 5 mg/mL. The finding indicates that AEPMF is safe and not toxic towards Vero cells. Screening by plaque reduction assay showed that AEPMF have antiviral activity against herpes simplex virus type 1 (HSV-1) with effective concentration (EC50) was 0.28 mg/mL. The selective index (SI=CC50/EC50) of AEPMF is 17.9 indicating AEPMF have potential for further evaluation in antiviral activity.

  20. Synthesis and anthelmintic activity of arctigenin derivatives against Dactylogyrus intermedius in goldfish.

    Science.gov (United States)

    Hu, Yang; Liu, Lei; Liu, Guang-Lu; Tu, Xiao; Wang, Gao-Xue; Ling, Fei

    2017-08-01

    To control the parasitic disease of Dactylogyrus intermedius, a series of new arctigenin derivatives were designed, synthesized and tested in our study. The anthelmintic activity of most of the derivatives ranged from 1 to 10mg/L. Compared to traditional drug praziquantel (EC 50 =2.69mg/L), ether derivatives 2g and 2h exhibited slightly higher anti-parasitic activity, with the EC 50 values of 2.48 and 1.52mg/L, respectively. Furthermore, the arctigenin-imidazole hybrids 4a and 4b also removed D. intermedius effectively, with the EC 50 values of 2.13 and 2.07mg/L, respectively. The structure-activity relationship analysis indicated that four carbon atoms length of linker and imidazole substitute group could significantly increase the anthelmintic activity, and reduced the toxicity. Through the scanning electron microscope observation, compounds 4a and 4b caused the D. intermedius tegumental damage such as intensive wrinkles, holes and nodular structures. Overall, the structural optimization analysis of arctigenin suggested that 4a and 4b can be used for preventing and controlling Dactylogyrus infections and considered as promising lead compounds for the development of commercial drugs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Antiviral activity of Petiveria alliacea against the bovine viral diarrhea virus.

    Science.gov (United States)

    Ruffa, M J; Perusina, M; Alfonso, V; Wagner, M L; Suriano, M; Vicente, C; Campos, R; Cavallaro, L

    2002-07-01

    Natural products are a relevant source of antiviral drugs. Five medicinal plants used in Argentina have been assayed to detect inhibition of viral growth. Antiviral activity of the infusions and methanolic extracts of Aristolochia macroura, Celtis spinosa, Plantago major, Schinus areira, Petiveria alliacea and four extracts obtained from the leaves and stems of the last plant were evaluated by the plaque assay. P. alliacea, unlike A. macroura, C. spinosa, P. major and S. areira, inhibited bovine viral diarrhea virus (BVDV) replication. Neither P. alliacea nor the assays of the other plants were active against herpes simplex virus type 1, poliovirus type 1, adenovirus serotype 7 and vesicular stomatitis virus type 1. Four extracts of P. alliacea were assayed to detect anti-BVDV activity. Ethyl acetate (EC(50) of 25 microg/ml) and dichloromethane (EC(50) of 43 microg/ml) extracts were active; moreover, promising SI (IC(50)/EC(50)) values were obtained. BVDV is highly prevalent in the cattle population, there are no antiviral compounds available; additionally, it is a viral model of the hepatitis C virus. For these reasons and in view of the results obtained, the isolation and characterization of the antiviral components present in the P. alliacea extracts is worth carrying out in the future. Copyright 2002 S. Karger AG, Basel

  2. In Vitro Antiviral Activity and Resistance Profile Characterization of the Hepatitis C Virus NS5A Inhibitor Ledipasvir.

    Science.gov (United States)

    Cheng, Guofeng; Tian, Yang; Doehle, Brian; Peng, Betty; Corsa, Amoreena; Lee, Yu-Jen; Gong, Ruoyu; Yu, Mei; Han, Bin; Xu, Simin; Dvory-Sobol, Hadas; Perron, Michel; Xu, Yili; Mo, Hongmei; Pagratis, Nikos; Link, John O; Delaney, William

    2016-01-11

    Ledipasvir (LDV; GS-5885), a component of Harvoni (a fixed-dose combination of LDV with sofosbuvir [SOF]), is approved to treat chronic hepatitis C virus (HCV) infection. Here, we report key preclinical antiviral properties of LDV, including in vitro potency, in vitro resistance profile, and activity in combination with other anti-HCV agents. LDV has picomolar antiviral activity against genotype 1a and genotype 1b replicons with 50% effective concentration (EC50) values of 0.031 nM and 0.004 nM, respectively. LDV is also active against HCV genotypes 4a, 4d, 5a, and 6a with EC50 values of 0.11 to 1.1 nM. LDV has relatively less in vitro antiviral activity against genotypes 2a, 2b, 3a, and 6e, with EC50 values of 16 to 530 nM. In vitro resistance selection with LDV identified the single Y93H and Q30E resistance-associated variants (RAVs) in the NS5A gene; these RAVs were also observed in patients after a 3-day monotherapy treatment. In vitro antiviral combination studies indicate that LDV has additive to moderately synergistic antiviral activity when combined with other classes of HCV direct-acting antiviral (DAA) agents, including NS3/4A protease inhibitors and the nucleotide NS5B polymerase inhibitor SOF. Furthermore, LDV is active against known NS3 protease and NS5B polymerase inhibitor RAVs with EC50 values equivalent to those for the wild type. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  3. Phytochemical screening, cytotoxicity and antiviral activity of hexane fraction of Phaleria macrocarpa fruits

    Science.gov (United States)

    Ismaeel, Mahmud Yusef Yusef; Yaacob, Wan Ahmad; Tahir, Mariya Mohd.; Ibrahim, Nazlina

    2015-09-01

    Phaleria macrocarpa fruits have been widely used in the traditional medicine for the treatment of several infections. The current study was done to determine the phytochemical content, cytotoxicity and antiviral activity of the hexane fraction (HF) of P. macrocarpa fruits. In the hexane fraction of P. macarocarpa fruits, phytochemical screening showed the presence of terpenoids whereas saponins, alkaloids, tannins and anthraquinones were not present. Evaluation on Vero cell lines by using MTT assay showed that the 50% cytotoxic concentration (CC50) value was 0.48 mg/mL indicating that the fraction is not cytotoxic. Antiviral properties of the plant extracts were determined by plaque reduction assay. The effective concentration (EC50) was 0.18 mg/mL. Whereas the selective index (SI = CC50/EC50) of hexane fraction is 2.6 indicating low to moderate potential as antiviral agent.

  4. Cytotoxicity and antiviral activities of Asplenium nidus, Phaleria macrocarpa and Eleusine indica

    Science.gov (United States)

    Tahir, Mariya Mohd; Ibrahim, Nazlina; Yaacob, Wan Ahmad

    2014-09-01

    Three local medicinal plants namely Asplenium nidus (langsuyar), Eleusine indica (sambau) and Phaleria macrocarpa (mahkota dewa) were screened for the cytotoxicity and antiviral activities. Six plant extracts were prepared including the aqueous and methanol extracts from A. nidus leaf and root, aqueous extract from dried whole plant of E. indica and methanol extract from P. macrocarpa fruits. Cytotoxicity screening in Vero cell line by MTT assay showed that the CC50 values ranged from 15 to 60 mg/mL thus indicating the safety of the extracts even at high concentrations. Antiviral properties of the plant extracts were determined by plaque reduction assay. The EC50 concentrations were between 3.2 to 47 mg/mL. The selectivity indices (SI = CC50/EC50) of each tested extracts ranged from 4.3 to 63.25 indicating the usefulness of the extracts as potential antiviral agents.

  5. Antioxidant activity from the leaf extracts of Jacaranda puberula Cham., Bignoniaceae, a Brazilian medicinal plant used for blood depuration

    Directory of Open Access Journals (Sweden)

    Paula Macedo Lessa dos Santos

    Full Text Available The antioxidant activity of leaf extracts from Jacaranda puberula Cham., Bignoniaceae, was assayed by the DPPH (2,2-diphenyl-1-picryl-hydrazyl free radical scavenging method. Three phytomedicines (F1, F2, and F3 used as blood depurative, were tested by the same method. The free radical scavenger potential was measured by the discoloration of the solution. The EC50 values from Gingko bilobaEGb 761® extract and rutin, used as antioxidant for medical purposes, were used as reference. The ethanol extract (EE, ethyl acetate (EA, butanol (EB, aqueous (EAq and the sample A (obtained from extract EB, showed lower EC50 values than other extracts and phytomedicines. The antioxidant activity (AA of the extracts was related with the presence of the polyphenol compounds such as verbascoside (1 and cis-caffeoyl aldehyde (2. These structures were determined by chemical and spectroscopic methods and comparison with literature data.

  6. Synthesis and biological activity of allosteric modulators of GABAB receptors part 3. 3-(2,6-bis-iso-propyl-4-hydroxyphenyl)propanols

    International Nuclear Information System (INIS)

    Kerr, David I.B.; Ong, Jennifer; Khalafy, Jabbar; Rimaz, Mehdi; Prager, Rolf H.

    2007-01-01

    A series of six 2,2-disubstituted 3-[3,5-di-iso-propyl-4-hydroxyphenyl]propan-1-ol derivatives have been prepared for evaluation as allosteric modulators of GABA B receptors. The activity (EC 50 30 μM) was greatest for the dimethyl analogue, but the isopropylphenyl compounds were generally weaker than the corresponding t-butyl compounds. Methylation of the phenolic group led to loss of activity. (author)

  7. Spasmogenic and spasmolytic activity of rind of Punica granatum Linn.

    Science.gov (United States)

    Ali, Niaz; Jamil, Ayesha; Shah, Syed Wadood Ali; Shah, Ismail; Ahmed, Ghayour

    2017-02-07

    Rind of Punica granatum is traditionally used in treatment of abdominal cramps and various GIT disorders. So far spasmolytic activity of rind of Punica granatum has been reported using in vitro model. However, its mode of action is not explored yet. Therefore, the current work describes the possible mode of action for spasmolytic activity of methanolic extract of rind of Punica granatum (Pg. Cr). Acute toxicity study is also performed to determine its safe dose range. Rind of Punica granatum was subjected to shade drying. Shade dried materials were pulverized using conventional grinder. Grinded materials were macerated in commercial grade methanol. The extract of rind of P. granatum was concentrated using a rotary evaporator. Rabbits' jejunal preparations were mounted in organ bath containing 10 ml Tyrode's solution, constantly aerated with carbogen gas. Pg. Cr was tested on spontaneous rabbits' jejunal preparations in concentrations 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, 5.0 and 10.0 mg/ml. Pg. Cr was also tested on KCl (80 mM)-induced contractions in rabbits' jejunal preparations. Since we observed spasmogenic activity for the first time, hence we also determined the effects of Pg. Cr in presence of atropine (0.03 μM). Pg. Cr was also tested in presence of 0.03 μM of loratadine HCl. Pg. Cr was also tested on barium chloride induced contractions. Calcium Concentration Response Curves (CCRCs) were constructed in the absence and presence of test samples of Pg. Cr in decalcified tissues to explore its possible mode of action. Acute toxicity screening was also performed to determine its safe dose range. Phytochemical screening revealed the presence of saponins, tannins, carbohydrates, proteins, flavonoids, saponins and steroids. However, Pg. Cr tested negative for alkaloids and triterpenoids. Pg. Cr was safe up to 100 mg/kg with its LD 50 = 1305 mg/kg. Its respective EC 50, in the absence and presence of atropine, were 9.7 ± 0.3 and 3.12 ± 0.45 mg/ml. In

  8. Allosteric activation of the follicle-stimulating hormone (FSH) receptor by selective, nonpeptide agonists.

    Science.gov (United States)

    Yanofsky, Stephen D; Shen, Emily S; Holden, Frank; Whitehorn, Erik; Aguilar, Barbara; Tate, Emily; Holmes, Christopher P; Scheuerman, Randall; MacLean, Derek; Wu, May M; Frail, Donald E; López, Francisco J; Winneker, Richard; Arey, Brian J; Barrett, Ronald W

    2006-05-12

    The pituitary glycoprotein hormones, luteinizing hormone and follicle-stimulating hormone (FSH), act through their cognate receptors to initiate a series of coordinated physiological events that results in germ cell maturation. Given the importance of FSH in regulating folliculogenesis and fertility, the development of FSH mimetics has been sought to treat infertility. Currently, purified and recombinant human FSH are the only FSH receptor (FSH-R) agonists available for infertility treatment. By screening unbiased combinatorial chemistry libraries, using a cAMP-responsive luciferase reporter assay, we discovered thiazolidinone agonists (EC50's = 20 microm) of the human FSH-R. Subsequent analog library screening and parallel synthesis optimization resulted in the identification of a potent agonist (EC50 = 2 nm) with full efficacy compared with FSH that was FSH-R-selective and -dependent. The compound mediated progesterone production in Y1 cells transfected with the human FSH-R (EC50 = 980 nm) and estradiol production from primary rat ovarian granulosa cells (EC50 = 10.5 nm). This and related compounds did not compete with FSH for binding to the FSH-R. Use of human FSH/thyroid-stimulating hormone (TSH) receptor chimeras suggested a novel mechanism for receptor activation through a binding site independent of the natural hormone binding site. This study is the first report of a high affinity small molecule agonist that activates a glycoprotein hormone receptor through an allosteric mechanism. The small molecule FSH receptor agonists described here could lead to an oral alternative to the current parenteral FSH treatments used clinically to induce ovarian stimulation for both in vivo and in vitro fertilization therapy.

  9. [Synthesis and biological activity of 2,3-secotriterpene acid mono- and diamides].

    Science.gov (United States)

    Tolmacheva, I A; Igosheva, E V; Vikharev, Iu B; Grishko, V V; Savinova, O V; Boreko, E I; Eremin, V F

    2013-01-01

    Four types of amide (C3; C28; C3-C28) conjugates based on 2,3-seco-18alphaH-oleanane and 2,3-secolupane mono- and dicarboxylic acids were synthesized. The range of diamide derivatives was supplemented with C3-C3' and C28-C28' dicondensed amides with two A-secotriterpene backbones educed by reacting monocarboxylic A-secoacids with biogenic amino acid lysine. Compounds with inhibitory action against herpes virus reproduction (EC50 8.7 and 4.1 McM) were found among the synthesized mono- and diamide derivatives containing an ethyl-beta-alaninate fragment. It has been ascertained that diamide with ethyl-beta-alaninate fragment combines anti-herpes virus properties and anti-HIV activity (EC50 5.1 McM). For active compounds, the maximum non-toxic concentration (MNTC)/EC50 ratios ranges from 9.7 to 40.8. The synthesized amide conjugates do not exhibit any marked cytotoxic effects against human tumor cell lines rabdomiosarcoma RD TE32, A549 lung carcinoma and melanoma MS.

  10. Comparative antioxidant activity of cultivated and wild Vaccinium species investigated by EPR, human neutrophil burst and COMET assay.

    Science.gov (United States)

    Braga, P C; Antonacci, R; Wang, Y Y; Lattuada, N; Dal Sasso, M; Marabini, L; Fibiani, M; Lo Scalzo, R

    2013-01-01

    The Vaccinium (V.) spp. berries are considered a source of antioxidants, mainly belonging to polyphenols, specifically flavonoids and anthocyanins. Wild genotypes generally contain more antioxidants than cultivated counterparts. So, seven different antioxidants assays on extracts from cultivated and wild Vaccinium berries were performed, to evaluate their difference in terms of bioactivity on oxidative protection and minimum dosage to have a significant action. Four cell-free antioxidant assays (ABTS radical scavenging and electronic paramagnetic resonance using Fremy's salt, superoxide anion and hydroxyl radical), and three assays on human cells (two luminol amplified chemiluminescence, LACL, one on DNA damage, COMET) were used to measure the effects of cultivated blueberry (V. corymbosum) and wild bilberry (V. myrtillus) on the differently induced oxidative stress. Concentrations vs activity patterns were obtained by successive dilutions of extracts in order to identify both EC50 and minimum significant activity (MSA). All the assays (except for the hydroxyl radical scavenging) showed a good relationship mainly with anthocyanin and polyphenol content and the significant greater activity of wild Vaccinium extracts. In fact, LACL data gave an EC50 of 11.8 and an MSA of 5.2 g were calculated as fresh weight dosage in cultivated berries, compared with lower doses in wild berries, EC50 of 5.7 g and MSA of 3.4 g. Wild Vaccinium extracts averaged 3.04 and 2.40 fold more activity than cultivated extracts by EC50 and MSA, respectively. COMET assay confirmed the stronger action on DNA protection in wild samples.

  11. In Vitro Antiviral Activity and Resistance Profile of the Next-Generation Hepatitis C Virus NS5A Inhibitor Pibrentasvir.

    Science.gov (United States)

    Ng, Teresa I; Krishnan, Preethi; Pilot-Matias, Tami; Kati, Warren; Schnell, Gretja; Beyer, Jill; Reisch, Thomas; Lu, Liangjun; Dekhtyar, Tatyana; Irvin, Michelle; Tripathi, Rakesh; Maring, Clarence; Randolph, John T; Wagner, Rolf; Collins, Christine

    2017-05-01

    Pibrentasvir (ABT-530) is a novel and pan-genotypic hepatitis C virus (HCV) NS5A inhibitor with 50% effective concentration (EC 50 ) values ranging from 1.4 to 5.0 pM against HCV replicons containing NS5A from genotypes 1 to 6. Pibrentasvir demonstrated similar activity against a panel of chimeric replicons containing HCV NS5A of genotypes 1 to 6 from clinical samples. Resistance selection studies were conducted using HCV replicon cells with NS5A from genotype 1a, 1b, 2a, 2b, 3a, 4a, 5a, or 6a at a concentration of pibrentasvir that was 10- or 100-fold over its EC 50 for the respective replicon. With pibrentasvir at 10-fold over the respective EC 50 , only a small number of colonies (0.00015 to 0.0065% of input cells) with resistance-associated amino acid substitutions were selected in replicons containing genotype 1a, 2a, or 3a NS5A, and no viable colonies were selected in replicons containing NS5A from other genotypes. With pibrentasvir at 100-fold over the respective EC 50 , very few colonies (0.0002% of input cells) were selected by pibrentasvir in genotype 1a replicon cells while no colonies were selected in other replicons. Pibrentasvir is active against common resistance-conferring substitutions in HCV genotypes 1 to 6 that were identified for other NS5A inhibitors, including those at key amino acid positions 28, 30, 31, or 93. The combination of pibrentasvir with HCV inhibitors of other classes produced synergistic inhibition of HCV replication. In summary, pibrentasvir is a next-generation HCV NS5A inhibitor with potent and pan-genotypic activity, and it maintains activity against common amino acid substitutions of HCV genotypes 1 to 6 that are known to confer resistance to currently approved NS5A inhibitors. Copyright © 2017 Ng et al.

  12. Brazilian savanna fruits contain higher bioactive compounds content and higher antioxidant activity relative to the conventional red delicious apple.

    Directory of Open Access Journals (Sweden)

    Egle Machado de Almeida Siqueira

    Full Text Available The bioactive compounds content and the antioxidant activity (AA of twelve fruits native to the Cerrado were compared with the Red Delicious apple by means of the antiradical efficiency (using the 2,2-diphenyl-1-picrylhydrazil assay/DPPH, ferric reducing antioxidant power (FRAP and the β-carotene/linoleic system. The antiradical efficiency (AE and the kinetic parameters (Efficient concentration/EC50 and time needed to reach the steady state to EC50 concentration/TEC50 of the DPPH curve were also evaluated for comparison with the Trolox equivalent (TE values. A strong, significant and positive correlation was observed between the TE and AE values, whereas a weak and negative correlation was observed between TE and EC50, suggesting that the values of AE and TE are more useful for the determination of antiradical activity in fruits than the widely used EC50. The total phenolic content found in the fruits corresponded positively to their antioxidant activity. The high content of bioactive compounds (flavanols, anthocyanins or vitamin C relative to the apple values found in araticum, cagaita, cajuzinho, jurubeba, lobeira, magaba and tucum corresponded to the high antioxidant activity of these fruits. Flavanols and anthocyanins may be the main bioactive components in these Cerrado fruits. The daily consumption of at least seven of the twelve Cerrado fruits studied, particularly, araticum, cagaita, lobeira and tucum, may confer protection against oxidative stress, and thus, they may prevent chronic diseases and premature aging. The findings of this study should stimulate demand, consumption and cultivation of Cerrado fruits and result in sustainable development of the region where this biome dominates.

  13. High performance liquid chromatography profiling of health-promoting phytochemicals and evaluation of antioxidant, anti-lipoxygenase, iron chelating and anti-glucosidase activities of wetland macrophytes.

    Science.gov (United States)

    Ooh, Keng-Fei; Ong, Hean-Chooi; Wong, Fai-Chu; Sit, Nam-Weng; Chai, Tsun-Thai

    2014-08-01

    The phytochemistry and bioactivity of wetland macrophytes are underexplored. Plants are known as the natural sources of phytochemical beneficial to health. The objective of this study is to analyze the phytochemical profiles and bioactivities of 10 extracts prepared from different plant parts of wetland macrophytes Hanguana malayana, Ludwigia adscendens and Monochoria hastata. High performance liquid chromatography (HPLC) was used to analyze the phytochemical profile of the extracts. Antioxidant assay such as 2,2-diphenyl-1-picrylhydrazyl, nitric oxide (NO) radical scavenging activity and ferric reducing antioxidant power were performed. Bioactivity assays carried out were anti-lipoxygenase, anti-glucosidase, and iron chelating. Leaf extract of L. adscendens had the highest 2,2-diphenyl-1-picrylhydrazyl (half of maximal effective concentration [EC50] =0.97 mg/mL) and NO (EC50 = 0.31 mg/mL) scavenging activities. The extract also exhibited the highest iron chelating (EC50 = 3.24 mg/mL) and anti-glucosidase (EC50 = 27.5 μg/mL) activities. The anti-glucosidase activity of L. adscendens leaf extract was comparable or superior to those of acarbose, myricetin and quercetin. Correlation between iron chelating and radical scavenging activities among the extracts implies the presence of dual-function phytoconstituents with concurrent iron chelating and radical scavenging activities. HPLC analysis revealed the presence of p-coumaric acid (p-CA), gallic acid (GA) and myricetin in all or most extracts. M. hastata fruit and leaf extracts had the highest p-hydroxybenzoic acid content. Antioxidant and anti-glucosidase activities of the extracts were correlated with p-CA, GA, and myricetin contents. Our study demonstrated that wetland macrophytes H. malayana, L. adscendens and M. hastata are potential sources of health-promoting phytochemicals with potent therapeutically-relevant bioactivities.

  14. High performance liquid chromatography profiling of health-promoting phytochemicals and evaluation of antioxidant, anti-lipoxygenase, iron chelating and anti-glucosidase activities of wetland macrophytes

    Science.gov (United States)

    Ooh, Keng-Fei; Ong, Hean-Chooi; Wong, Fai-Chu; Sit, Nam-Weng; Chai, Tsun-Thai

    2014-01-01

    Background: The phytochemistry and bioactivity of wetland macrophytes are underexplored. Plants are known as the natural sources of phytochemical beneficial to health. Objective: The objective of this study is to analyze the phytochemical profiles and bioactivities of 10 extracts prepared from different plant parts of wetland macrophytes Hanguana malayana, Ludwigia adscendens and Monochoria hastata. Materials and Methods: High performance liquid chromatography (HPLC) was used to analyze the phytochemical profile of the extracts. Antioxidant assay such as 2,2-diphenyl-1-picrylhydrazyl, nitric oxide (NO) radical scavenging activity and ferric reducing antioxidant power were performed. Bioactivity assays carried out were anti-lipoxygenase, anti-glucosidase, and iron chelating. Results: Leaf extract of L. adscendens had the highest 2,2-diphenyl-1-picrylhydrazyl (half of maximal effective concentration [EC50] =0.97 mg/mL) and NO (EC50 = 0.31 mg/mL) scavenging activities. The extract also exhibited the highest iron chelating (EC50 = 3.24 mg/mL) and anti-glucosidase (EC50 = 27.5 μg/mL) activities. The anti-glucosidase activity of L. adscendens leaf extract was comparable or superior to those of acarbose, myricetin and quercetin. Correlation between iron chelating and radical scavenging activities among the extracts implies the presence of dual-function phytoconstituents with concurrent iron chelating and radical scavenging activities. HPLC analysis revealed the presence of p-coumaric acid (p-CA), gallic acid (GA) and myricetin in all or most extracts. M. hastata fruit and leaf extracts had the highest p-hydroxybenzoic acid content. Antioxidant and anti-glucosidase activities of the extracts were correlated with p-CA, GA, and myricetin contents. Conclusion: Our study demonstrated that wetland macrophytes H. malayana, L. adscendens and M. hastata are potential sources of health-promoting phytochemicals with potent therapeutically-relevant bioactivities. PMID:25298659

  15. Determination and quantification of the in vitro activity of Aloe marlothii (A. Berger subsp. marlothii and Elephantorrhiza elephantina (Burch. skeels acetone extracts against Ehrlichia ruminantium

    Directory of Open Access Journals (Sweden)

    V. Naidoo

    2006-09-01

    Full Text Available An Ehrlichia ruminantium culture system was utilized for the anti-rickettsial evaluation of two ethnoveterinary plants, Elephantorrhiza elephantina and Aloe marlothii. Well-established E. ruminantium cultures were incubated with the plant leaf acetone extracts and compared to oxytetracycline and untreated controls. Effectivity was established by comparing the percentage parasitised cells and the calculation of both EC50 and extrapolated EC90 in µg/ml. The plant extracts were also screened for antibacterial activity using bioautography. Elephantorrhiza elephantina and A. marlothii demonstrated anti-ehrlichial activity with an EC50 of 111.4 and 64.5 µg/ml and EC 90 of 228.9 and 129.9 µg/ml, respectively. The corresponding EC50 and EC90 for oxytetracycline was 0.29 and 0.08 µg/ml. Both plants appeared to produce their inhibitory activity by a similar mechanism, unrelated to that of the tetracyclines. Both the plant acetone extracts demonstrated antibacterial activity against Escherichia coli and Staphylococcus aureus (ATCC strains.

  16. Investigation on Antibacterial and Antioxidant Activities, Phenolic and Flavonoid Contents of Some Thai Edible Plants as an Alternative for Antibiotics

    Directory of Open Access Journals (Sweden)

    J. H. Lee

    2014-10-01

    Full Text Available This study was aimed to examine the antibacterial and antioxidative properties of seven edible plants from Thailand to develop alternative antibiotics as feed additives. The plants include Citrus aurantifolia Swingle (Lime fruits and its leaves, Sesbania grandiflora L. (Agati sesbania leaves, Piper sarmentosum Roxb (Wild betal leaves, Curcuma domestica Valeton (Turmeric roots, Morinda citrifolia L. (Beach mulberry leaves, Cassia siamea britt (Siamea cassia leaves, and Cocos nucifera L. (Coconut peels. The plants were extracted by methanol, n-hexane, chloroform, ethyl acetate, butanol and water. Antibacterial activities with minimum inhibitory concentration (MIC were determined by agar diffusion assay against Escherichia coli, Burkholderia sp., Haemopilus somnus, Haemopilus parasuis, and Clostridium perfringens that were considered pathogenic strains in livestock infection. Methanol extracts of C. aurantifolia Swingle fruits and leaves showed the broadest spectrum of antibacterial activities except for C. perfringens. Butanol extract of S. grandiflora L. leaves showed the strongest activity against Burkholderia sp. with MIC, 135 μg/mL. P. sarmentosum Roxb leaves showed antibacterial activities against E. coli, Burkholderia sp. and H. parasuis. Ethyl acetate and water extracts from C. domesitca Valeton roots showed MIC of 306 μg/mL and 183 μg/mL, respectively against only C. perfringens. Antioxidative activity was determined by 2-diphenyl-2-picryl hydrazyl photometric assay. The methanol extracts of C. aurantifolia Swingle fruits and P. sarmentosum Roxb leaves showed the highest antioxidant activity among all the extracts with 3.46 mg/mL and 2.70 mg/mL effective concentration 50% (EC50 values, respectively. Total contents of phenolics and flavonoids were measured from the plant extracts. Methanol extracts of S. grandiflora L. and chloroform extracts of C. domestica Valeton were found to have the highest amount of total phenolics, 41.7 and 47

  17. Alpha-glucosidase Inhibitory and Antioxidant Potential of Antidiabetic Herb Alternanthera sessilis: Comparative Analyses of Leaf and Callus Solvent Fractions.

    Science.gov (United States)

    Chai, Tsun-Thai; Khoo, Chee-Siong; Tee, Chong-Siang; Wong, Fai-Chu

    2016-01-01

    Alternanthera sessilis is a medicinal herb which is consumed as vegetable and used as traditional remedies of various ailments in Asia and Africa. This study aimed to investigate the antiglucosidase and antioxidant activity of solvent fractions of A. sessilis leaf and callus. Leaf and callus methanol extracts were fractionated to produce hexane, chloroform, ethyl acetate, butanol, and water fractions. Antiglucosidase and 1,1-diphenyl-2-picrylhydrazyl scavenging activities as well as total phenolic (TP), total flavonoid (TF), and total coumarin (TC) contents were evaluated. Lineweaver-Burk plot analysis was performed on leaf and callus fractions with the strongest antiglucosidase activity. Leaf ethyl acetate fraction (LEF) had the strongest antiglucosidase (EC 50 0.55 mg/mL) and radical scavenging (EC 50 10.81 μg/mL) activity among leaf fractions. Callus ethyl acetate fraction (CEF) and chloroform fraction had the highest antiglucosidase (EC 50 0.25 mg/mL) and radical scavenging (EC 50 34.12 μg/mL) activity, respectively, among callus fractions. LEF and CEF were identified as noncompetitive and competitive α-glucosidase inhibitors, respectively. LEF and CEF had greater antiglucosidase activity than acarbose. Leaf fractions had higher phytochemical contents than callus fractions. LEF had the highest TP, TF, and TC contents. Antiglucosidase and antioxidant activities of leaf fractions correlated with phytochemical contents. LEF had potent antiglucosidase activity and concurrent antioxidant activity. CEF had the highest antiglucosidase activity among all fractions. Callus culture is a promising tool for enhancing production of potent α-glucosidase inhibitors. Leaf ethyl acetate fraction (LEF) had the strongest antiglucosidase (EC 50 0.55 mg/mL) and radical scavenging (EC 50 10.81 μg/mL) activity among leaf fractionsCallus ethyl acetate fraction (CEF) and chloroform fraction had the highest antiglucosidase (EC 50 0.25 mg/mL) and radical scavenging (EC 50 34.12

  18. Automated evaluation of pharmaceutically active ionic liquids’ (eco)toxicity through the inhibition of human carboxylesterase and Vibrio fischeri

    International Nuclear Information System (INIS)

    Costa, Susana P.F.; Justina, Vanessa D.; Bica, Katharina; Vasiloiu, Maria; Pinto, Paula C.A.G.; Saraiva, M. Lúcia M.F.S.

    2014-01-01

    Highlights: • IL-APIs toxicity on humans and aquatic environment was evaluated by inhibition assays. • The inhibition assays were implemented through automated screening bioassays. • Automation of bioassays enabled a rigorous control of the reaction conditions. • EC 50 obtained provide vital information on IL-APIs safety and potential use as drugs. -- Abstract: The toxicity of 16 pharmaceutical active ionic liquids (IL-APIs) was evaluated by automated approaches based on sequential injection analysis (SIA). The implemented bioassays were centered on the inhibition of human carboxylesterase 2 and Vibrio fischeri, in the presence of the tested compounds. The inhibitory effects were quantified by calculating the inhibitor concentration required to cause 50% of inhibition (EC 50 ). The EC 50 values demonstrated that the cetylpyridinium group was one of the most toxic cations and that the imidazolium group was the less toxic. The obtained results provide important information about the safety of the studied IL-APIs and their possible use as pharmaceutical drugs. The developed automated SIA methodologies are robust screening bioassays, and can be used as a generic tools to identify the (eco)toxicity of the structural elements of ILs, contributing to a sustainable development of drugs

  19. Design, Synthesis, and Antifouling Activity of Glucosamine-Based Isocyanides.

    Science.gov (United States)

    Umezawa, Taiki; Hasegawa, Yuki; Novita, Ira S; Suzuki, Junya; Morozumi, Tatsuya; Nogata, Yasuyuki; Yoshimura, Erina; Matsuda, Fuyuhiko

    2017-06-29

    Biofouling, an undesirable accumulation of organisms on sea-immersed structures such as ship hulls and fishing nets, is a serious economic issue whose effects include oil wastage and clogged nets. Organotin compounds were utilized since the 1960s as an antifouling material; however, the use of such compounds was later banned by the International Maritime Organization (IMO) due to their high toxicity toward marine organisms, resulting in masculinization and imposex. Since the ban, there have been extensive efforts to develop environmentally benign antifoulants. Natural antifouling products obtained from marine creatures have been the subject of considerable attention due to their potent antifouling activity and low toxicity. These antifouling compounds often contain isocyano groups, which are well known to have natural antifouling properties. On the basis of our previous total synthesis of natural isocyanoterpenoids, we envisaged the installation of an isocyano functional group onto glucosamine to produce an environmentally friendly antifouling material. This paper describes an effective synthetic method for various glucosamine-based isocyanides and evaluation of their antifouling activity and toxicity against cypris larvae of the barnacle Amphibalanus amphitrite . Glucosamine isocyanides with an ether functionality at the anomeric position exhibited potent antifouling activity, with EC 50 values below 1 μg/mL, without detectable toxicity even at a high concentration of 10 μg/mL. Two isocyanides had EC 50 values of 0.23 and 0.25 μg/mL, comparable to that of CuSO₄, which is used as a fouling inhibitor (EC 50 = 0.27 μg/mL).

  20. Double positivity for HPV-DNA/p16ink4a is the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patients.

    Science.gov (United States)

    Mena, Marisa; Taberna, Miren; Tous, Sara; Marquez, Sandra; Clavero, Omar; Quiros, Beatriz; Lloveras, Belen; Alejo, Maria; Leon, Xavier; Quer, Miquel; Bagué, Silvia; Mesia, Ricard; Nogués, Julio; Gomà, Montserrat; Aguila, Anton; Bonfill, Teresa; Blazquez, Carmen; Guix, Marta; Hijano, Rafael; Torres, Montserrat; Holzinger, Dana; Pawlita, Michael; Pavon, Miguel Angel; Bravo, Ignacio G; de Sanjosé, Silvia; Bosch, Francesc Xavier; Alemany, Laia

    2018-03-01

    The etiologic role of human papillomaviruses (HPV) in oropharyngeal cancer (OPC) is well established. Nevertheless, information on survival differences by anatomic sub-site or treatment remains scarce, and it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. We conducted a retrospective cohort study of all patients diagnosed with a primary OPC in four Catalonian hospitals from 1990 to 2013. Formalin-fixed, paraffin-embedded cancer tissues were subjected to histopathological evaluation, DNA quality control, HPV-DNA detection, and p16 INK4a /pRb/p53/Cyclin-D1 immunohistochemistry. HPV-DNA positive and a random sample of HPV-DNA negative cases were subjected to HPV-E6*I mRNA detection. Demographic, tobacco/alcohol use, clinical and follow-up data were collected. Multivariate models were used to evaluate factors associated with HPV positivity as defined by four different HPV-relatedness definitions. Proportional-hazards models were used to compare the risk of death and recurrence among HPV-related and non-related OPC. 788 patients yielded a valid HPV-DNA result. The percentage of positive cases was 10.9%, 10.2%, 8.5% and 7.4% for p16 INK4a , HPV-DNA, HPV-DNA/HPV-E6*I mRNA, and HPV-DNA/p16 INK4a , respectively. Being non-smoker or non-drinker was consistently associated across HPV-relatedness definitions with HPV positivity. A suggestion of survival differences between anatomic sub-sites and treatments was observed. Double positivity for HPV-DNA/p16 INK4a showed strongest diagnostic accuracy and prognostic value. Double positivity for HPV-DNA/p16 INK4a , a test that can be easily implemented in the clinical practice, has optimal diagnostic accuracy and prognostic value. Our results have strong clinical implications for patients' classification and handling and also suggest that not all the HPV-related OPC behave similarly. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Quantitative structure-activity relationships for chronic toxicity of alkyl-chrysenes and alkyl-benz[a]anthracenes to Japanese medaka embryos (Oryzias latipes).

    Science.gov (United States)

    Lin, Hongkang; Morandi, Garrett D; Brown, R Stephen; Snieckus, Victor; Rantanen, Toni; Jørgensen, Kåre B; Hodson, Peter V

    2015-02-01

    Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are a class of compounds found at significant concentrations in crude oils, and likely the main constituents responsible for the chronic toxicity of oil to fish. Alkyl substituents at different locations on the aromatic rings change the size and shape of PAH molecules, which results in different interactions with tissue receptors and different severities of toxicity. The present study is the first to report the toxicity of several alkylated derivatives of chrysene and benz[a]anthracene to the embryos of Japanese medaka (Oryzias latipes) using the partition controlled delivery (PCD) method of exposure. The PCD method maintained the desired exposure concentrations by equilibrium partitioning of hydrophobic test compounds from polydimethylsiloxane (PDMS) films. Test concentrations declined by only 13% over a period of 17 days. Based on the prevalence of signs of blue sac disease (BSD), as expressed by median effective concentrations (EC50s), benz[a]anthracene (B[a]A) was more toxic than chrysene. Alkylation generally increased toxicity, except at position 2 of B[a]A. Alkyl-PAHs substituted in the middle region had a lower EC50 than those substituted at the distal region. Except for B[a]A and 7-methylbenz[a]anthracene (7-MB), estimated EC50 values were higher than their solubility limits, which resulted in limited toxicity within the range of test concentrations. The regression between log EC50s and logKow values provided a rough estimation of structure-activity relationships for alkyl-PAHs, but Kow alone did not provide a complete explanation of the chronic toxicity of alkyl PAHs. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Activities of Jatropha curcas phorbol esters in various bioassays.

    Science.gov (United States)

    Devappa, Rakshit K; Rajesh, Sanjay K; Kumar, Vikas; Makkar, Harinder P S; Becker, Klaus

    2012-04-01

    Jatropha curcas seeds contain 30-35% oil, which can be converted to high quality biodiesel. However, Jatropha oil is toxic, ascribed to the presence of phorbol esters (PEs). In this study, isolated phorbol ester rich fraction (PEEF) was used to evaluate the activity of PEs using three aquatic species based bioassays (snail (Physa fontinalis), brine shrimp (Artemeia salina), daphnia (Daphnia magna)) and microorganisms. In all the bioassays tested, increase in concentration of PEs increased mortality with an EC(50) (48 h) of 0.33, 26.48 and 0.95 mg L(-1) PEs for snail, artemia and daphnia, respectively. The sensitivity of various microorganisms for PEs was also tested. Among the bacterial species tested, Streptococcus pyogenes and Proteus mirabilis were highly susceptible with a minimum inhibitory concentration (MIC) of 215 mg L(-1) PEs; and Pseudomonas putida were also sensitive with MIC of 251 mg L(-1) PEs. Similarly, Fusarium species of fungi exhibited EC(50) of 58 mg L(-1) PEs, while Aspergillus niger and Curvularia lunata had EC(50) of 70 mg L(-1). The snail bioassay was most sensitive with 100% snail mortality at 1 μg of PEs mL(-1). In conclusion, snail bioassay could be used to monitor PEs in Jatropha derived products such as oil, biodiesel, fatty acid distillate, kernel meal, cake, glycerol or for contamination in soil or other environmental matrices. In addition, PEs with molluscicidal/antimicrobial activities could be utilized for agricultural and pharmaceutical applications. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Olive Mill Waste Extracts: Polyphenols Content, Antioxidant, and Antimicrobial Activities

    Directory of Open Access Journals (Sweden)

    Inass Leouifoudi

    2015-01-01

    Full Text Available Natural polyphenols extracts have been usually associated with great bioactive properties. In this work, we investigated in vitro antioxidant and antimicrobial potential of the phenolic olive mill wastewater extracts (OWWE and the olive cake extracts (OCE. Using the Folin Ciocalteux method, OWWE contained higher total phenol content compared to OCE (8.90±0.728 g/L versus 0.95±0.017 mg/g. The phenolic compounds identification was carried out with a performance liquid chromatograph coupled to tandem mass spectrometry equipment (HPLC-ESI-MS. With this method, a list of polyphenols from OWWE and OCE was obtained. The antioxidant activity was measured in aqueous (DPPH and emulsion (BCBT systems. Using the DPPH assay, the results show that OWWE was more active than OCE and interestingly the extracts originating from mountainous areas were more active than those produced from plain areas (EC50=12.1±5.6 μg/mL; EC50=157.7±34.9 μg/mL, resp.. However, when the antioxidant activity was reversed in the BCBT, OCE produced from plain area was more potent than mountainous OCE. Testing by the gel diffusion assay, all the tested extracts have showed significant spectrum antibacterial activity against Staphylococcus aureus, whereas the biophenols extracts showed more limited activity against Escherichia coli and Streptococcus faecalis.

  4. Novel phenolic inhibitors of small/intermediate-conductance Ca²⁺-activated K⁺ channels, KCa3.1 and KCa2.3.

    Directory of Open Access Journals (Sweden)

    Aida Oliván-Viguera

    Full Text Available BACKGROUND: KCa3.1 channels are calcium/calmodulin-regulated voltage-independent K(+ channels that produce membrane hyperpolarization and shape Ca(2+-signaling and thereby physiological functions in epithelia, blood vessels, and white and red blood cells. Up-regulation of KCa3.1 is evident in fibrotic and inflamed tissues and some tumors rendering the channel a potential drug target. In the present study, we searched for novel potent small molecule inhibitors of KCa3.1 by testing a series of 20 selected natural and synthetic (polyphenols, synthetic benzoic acids, and non-steroidal anti-inflammatory drugs (NSAIDs, with known cytoprotective, anti-inflammatory, and/or cytostatic activities. METHODOLOGY/PRINCIPAL FINDINGS: In electrophysiological experiments, we identified the natural phenols, caffeic acid (EC50 1.3 µM and resveratrol (EC50 10 µM as KCa3.1 inhibitors with moderate potency. The phenols, vanillic acid, gallic acid, and hydroxytyrosol had weak or no blocking effects. Out of the NSAIDs, flufenamic acid was moderately potent (EC50 1.6 µM, followed by mesalamine (EC50≥10 µM. The synthetic fluoro-trivanillic ester, 13b ([3,5-bis[(3-fluoro-4-hydroxy-benzoyloxymethyl]phenyl]methyl 3-fluoro-4-hydroxy-benzoate, was identified as a potent mixed KCa2/3 channel inhibitor with an EC50 of 19 nM for KCa3.1 and 360 pM for KCa2.3, which affected KCa1.1 and Kv channels only at micromolar concentrations. The KCa3.1/KCa2-activator SKA-31 antagonized the 13b-blockade. In proliferation assays, 13b was not cytotoxic and reduced proliferation of 3T3 fibroblasts as well as caffeic acid. In isometric vessel myography, 13b increased contractions of porcine coronary arteries to serotonin and antagonized endothelium-derived hyperpolarization-mediated vasorelaxation to pharmacological KCa3.1/KCa2.3 activation. CONCLUSIONS/SIGNIFICANCE: We identified the natural phenols, caffeic acid and resveratrol, the NSAID, flufenamic acid, and the polyphenol 13b as novel

  5. Potentiated virucidal activity of pomegranate rind extract (PRE and punicalagin against Herpes simplex virus (HSV when co-administered with zinc (II ions, and antiviral activity of PRE against HSV and aciclovir-resistant HSV.

    Directory of Open Access Journals (Sweden)

    David M J Houston

    Full Text Available There is a clinical need for new therapeutic products against Herpes simplex virus (HSV. The pomegranate, fruit of the tree Punica granatum L, has since ancient times been linked to activity against infection. This work probed the activity of pomegranate rind extract (PRE and co-administered zinc (II ions.PRE was used in conjunction with zinc (II salts to challenge HSV-1 and aciclovir-resistant HSV in terms of virucidal plaque assay reduction and antiviral activities in epithelial Vero host cells. Cytotoxicity was determined by the MTS assay using a commercial kit.Zinc sulphate, zinc citrate, zinc stearate and zinc gluconate demonstrated similar potentiated virucidal activity with PRE against HSV-1 by up to 4-fold. A generally parabolic relationship was observed when HSV-1 was challenged with PRE and varying concentrations of ZnSO4, with a maximum potentiation factor of 5.5. Punicalagin had 8-fold greater virucidal activity than an equivalent mass of PRE. However, antiviral data showed that punicalagin had significantly lower antiviral activity compared to the activity of PRE (EC50 = 0.56 μg mL-1 a value comparable to aciclovir (EC50 = 0.18 μg mL-1; however, PRE also demonstrated potency against aciclovir-resistant HSV (EC50 = 0.02 μg mL-1, whereas aciclovir showed no activity. Antiviral action of PRE was not influenced by ZnSO4. No cytotoxicity was detected with any test solution.The potentiated virucidal activity of PRE by coadministered zinc (II has potential as a multi-action novel topical therapeutic agent against HSV infections, such as coldsores.

  6. Secondary Metabolites from Vietnamese Marine Invertebrates with Activity against Trypanosoma brucei and T. cruzi

    Directory of Open Access Journals (Sweden)

    Nguyen Phuong Thao

    2014-06-01

    Full Text Available Marine-derived natural products from invertebrates comprise an extremely diverse and promising source of the compounds from a wide variety of structural classes. This study describes the discovery of five marine natural products with activity against Trypanosoma species by natural product library screening using whole cell in vitro assays. We investigated the anti-trypanosomal activity of the extracts from the soft corals and echinoderms living in Vietnamese seas. Of the samples screened, the methanolic extracts of several marine organisms exhibited potent activities against cultures of Trypanosoma brucei and T. cruzi (EC50 < 5.0 μg/mL. Among the compounds isolated from these extracts, laevigatol B (1 from Lobophytum crassum and L. laevigatum, (24S-ergost-4-ene-3-one (2 from Sinularia dissecta, astropectenol A (3 from Astropecten polyacanthus, and cholest-8-ene-3β,5α,6β,7α-tetraol (4 from Diadema savignyi showed inhibitory activity against T. brucei with EC50 values ranging from 1.57 ± 0.14 to 14.6 ± 1.36 μM, relative to the positive control, pentamidine (EC50 = 0.015 ± 0.003 μM. Laevigatol B (1 and 5α-cholest-8(14-ene-3β,7α-diol (5 exhibited also significant inhibitory effects on T. cruzi. The cytotoxic activity of the pure compounds on mammalian cells was also assessed and found to be insignificant in all cases. This is the first report on the inhibitory effects of marine organisms collected in Vietnamese seas against Trypanosoma species responsible for neglected tropical diseases.

  7. Antifouling Activity of Secondary Metabolites Isolated from Chinese Marine Organisms

    KAUST Repository

    Li, Yong Xin

    2013-04-25

    Biofouling results in tremendous economic losses to maritime industries around the world. A recent global ban on the use of organotin compounds as antifouling agents has further raised demand for safe and effective antifouling compounds. In this study, 49 secondary metabolites, including diterpenoids, steroids, and polyketides, were isolated from soft corals, gorgonians, brown algae, and fungi collected along the coast of China, and their antifouling activity was tested against cyprids of the barnacle Balanus (Amphibalanus) amphitrite. Twenty of the compounds were found to inhibit larval settlement significantly at a concentration of 25 μg ml-1. Two briarane diterpenoids, juncin O (2) and juncenolide H (3), were the most promising non-toxic antilarval settlement candidates, with EC50 values less than 0.13 μg ml-1 and a safety ratio (LC50/EC50) higher than 400. A preliminary structure-activity relationships study indicated that both furanon and furan moieties are important for antifouling activity. Intriguingly, the presence of hydroxyls enhanced their antisettlement activity. © 2013 Springer Science+Business Media New York.

  8. Antifouling Activity of Secondary Metabolites Isolated from Chinese Marine Organisms

    KAUST Repository

    Li, Yong Xin; Wu, Hui Xian; Xu, Ying; Shao, Chang Lun; Wang, Chang Yun; Qian, Pei Yuan

    2013-01-01

    Biofouling results in tremendous economic losses to maritime industries around the world. A recent global ban on the use of organotin compounds as antifouling agents has further raised demand for safe and effective antifouling compounds. In this study, 49 secondary metabolites, including diterpenoids, steroids, and polyketides, were isolated from soft corals, gorgonians, brown algae, and fungi collected along the coast of China, and their antifouling activity was tested against cyprids of the barnacle Balanus (Amphibalanus) amphitrite. Twenty of the compounds were found to inhibit larval settlement significantly at a concentration of 25 μg ml-1. Two briarane diterpenoids, juncin O (2) and juncenolide H (3), were the most promising non-toxic antilarval settlement candidates, with EC50 values less than 0.13 μg ml-1 and a safety ratio (LC50/EC50) higher than 400. A preliminary structure-activity relationships study indicated that both furanon and furan moieties are important for antifouling activity. Intriguingly, the presence of hydroxyls enhanced their antisettlement activity. © 2013 Springer Science+Business Media New York.

  9. Exploration of the anti-enterovirus activity of a series of pleconaril/pirodavir-like compounds.

    Science.gov (United States)

    Bernard, Angela; Lacroix, Céline; Cabiddu, Maria G; Neyts, Johan; Leyssen, Pieter; Pompei, Raffaello

    2015-04-01

    The Enterovirus genus of the Picornaviridae is represented by several viral pathogens that are associated with human disease, namely Poliovirus 1, Enterovirus 71 and Rhinoviruses. Enterovirus 71 has been associated with encephalitis, while Rhinoviruses are a major cause of asthma exacerbations and chronic obstructive pulmonary disease. Based on the structure of both pleconaril and pirodavir, we previously synthesized some original compounds as potential inhibitors of Rhinovirus replication. These compounds were explored for in vitro antiviral potential on other human pathogenic Enteroviruses, namely Enterovirus 71 on rhabdo-myosarcoma cells, Coxsackievirus B3 on Vero cells, Poliovirus 1 and Echovirus 11 on BGM cells. Activity was confirmed for compound against Rhinovirus 14. Furthermore, few compounds showed a cell-protective effect on Enterovirus 71, presented a marked improvement as compared to the reference drug pleconaril for inhibitory activity on both Enterovirus 71 and Poliovirus 1. The most striking observation was the clear cell protective effect for the set of analogues in a virus-cell-based assay for Echovirus 11 with an effective concentration (EC50) as low as 0.3 µM (Selectivity index or SI = 483), and selectivity indexes greater than 857 (EC50 = 0.6 µM) and 1524 (EC50 = 0.33 µM). Some of the evaluated compounds showed potent and selective antiviral activity against several enterovirus species, such as Enterovirus 71 (EV-A), Echovirus 11 (EV-B), and Poliovirus 1 (EV-C). This could be used as a starting point for the development of other pleconaril/pirodavir-like enterovirus inhibitors with broad-spectrum activity and improved effects as compared to the reference drugs. © The Author(s) 2015.

  10. Antioxidative, Antiproliferative and Antimicrobial Activities of Phenolic Compounds from Three Myrcia Species

    Directory of Open Access Journals (Sweden)

    Catarina dos Santos

    2018-04-01

    Full Text Available Myrcia bella Cambess., Myrcia fallax (Rich. DC. and Myrcia guianensis (Aubl. DC. (Myrtaceae are trees found in Brazilian Cerrado. They have been widely used in folk medicine for the treatment of gastrointestinal disorders, hemorrhagic and infectious diseases. Few reports have been found in the literature connecting their phenolic composition and biological activities. In this regard, we have profiled the main phenolic constituents of Myrcia spp. leaves extracts by ESI(−Q-TOF-MS. The main constituents found were ellagic acid (M. bella, galloyl glucose isomers (M. guianensis and hexahydroxydiphenic (HHDP acid derivatives (M. fallax. In addition, quercetin and myricetin derivatives were also found in all Myrcia spp. extracts. The most promising antioxidant activity, measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH scavenging activity, was found for M. fallax extracts (EC50 8.61 ± 0.22 µg·mL−1, being slightly less active than quercetin and gallic acid (EC50 2.96 ± 0.17 and 2.03 ± 0.02 µg·mL−1, respectively. For in vitro antiproliferative activity, M. guianensis showed good activity against leukemia (K562 TGI = 7.45 µg·mL−1. The best antimicrobial activity was observed for M. bella and M. fallax to Escherichia coli (300 and 250 µg·mL−1, respectively. In conclusion, the activities found are closely related to the phenolic composition of these plants.

  11. Chemical composition and anti-herpes simplex virus type 1 (HSV-1) activity of extracts from Cornus canadensis.

    Science.gov (United States)

    Lavoie, Serge; Côté, Isabelle; Pichette, André; Gauthier, Charles; Ouellet, Michaël; Nagau-Lavoie, Francine; Mshvildadze, Vakhtang; Legault, Jean

    2017-02-22

    Many plants of boreal forest of Quebec have been used by Native Americans to treat a variety of microbial infections. However, the antiviral activities of these plants have been seldom evaluated on cellular models to validate their in vitro efficiencies. In this study, Cornus canadensis L. (Cornaceae), a plant used in Native American traditional medicine to treat possible antiviral infections, has been selected for further examination. The plant was extracted by decoction and infusion with water, water/ethanol 1:1 and ethanol to obtain extracts similar to those used by Native Americans. The effects of the extracts were tested on herpes simplex virus type-1 (HSV-1) using a plaque reduction assay. Moreover, bioassay-guided fractionation was achieved to isolate bioactive compounds. Water/ethanol 1:1 infusion of C. canadensis leaves were the most active extracts to inhibit virus absorption with EC 50 of about 9 μg mL -1 , whereas for direct mode, both extraction methods using water or water/ethanol 1:1 as solvent were relatively similar with EC 50 ranging from 11 to 17 μg mL -1 . The fractionation led to the identification of active fractions containing hydrolysable tannins. Tellimagrandin I was found the most active compound with an EC 50 of 2.6 μM for the direct mode and 5.0 μM for the absorption mode. Altogether, the results presented in this work support the antiviral activity of Cornus canadensis used in Native American traditional medicine.

  12. Apoptosis caused by triterpenes and phytosterols and antioxidant activity of an enriched flavonoid extract and from Passiflora mucronata.

    Science.gov (United States)

    da Silva, Isabel Cristina Vieira; Kaluderovic, Goran; de Oliveira, Pollyana Felix; Guimaraes, Denise Oliveira; Quaresma, Carla Holandino; Porzel, Andrea; Muzitano, Michelle Frazao; Wessjohann, Ludger A; Leal, Ivana Correa Ramos

    2018-03-14

    The genus Passiflora is knew for food consumption mainly and it extracts present a variety of methabolites, including flavones, alkaloids and triterpenes usually correlated with their antioxidant and antitumoral activities. P. mucronata (Pm) is from Brazil South America and is characterized as "Maracujá de Restinga", being used in the folk medicine for treating insomnia and soothing. The present study evaluated in the first time, the antioxidant and cytotoxicity of the hydroalcoholic leaves extract and fractions from Pm. Their cytotoxic effects were against human prostate cancer (PC3) and mouse malignant melanoma (B16F10) cell lines, by the MTT and CV assays. β-Amyrin, oleanolic acid, β-sitosterol and stigmasterol were isolated as the main components of the most active hexane fraction. These substances were tested individually against the tumor cell lines, whereby β-sitosterol and stigmasterol showed the most relevant activity to PC3 in CV assay and, oleanolic acid to B16F10 by the MTT assay. In addition, these compounds were analysed to cell cycle arrest, and stigmasterol decreased the number of cells in B16F10 line in the G1/G0 phase and subsequently, increased the cell number in sub-G1 phase, presumably indicating apoptosis as possible mode of cell death.The antioxidant activity by the DPPH method showed that the hydroalcoholic extract from the leaves presented higher antioxidant activity (EC50= 133.3 µg/mL) compared to the flowers (EC50= 152.3 µg/mL) and fruits (EC50=207.9 µg/mL) extracts. By the HPLC-MS it was possible to identify the main flavones present in the leaf extract (isoschaftoside, schaftoside, isovitexin, vitexin, isoorientin, orientin). Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Chemical constituents and antioxidant activity from leaves extracts of Terminalia fagifolia Mart. et Zucc

    International Nuclear Information System (INIS)

    Ayres, Mariane Cruz Costa; Chaves, Mariana H.; Rinaldo, Daniel; Vilegas, Wagner; Vieira Junior, Gerardo Magela

    2009-01-01

    Phytochemical investigation of ethanolic leaves extracts of T. fagifolia led to the isolation of (+)-catechin, sitosterol-3-O-β-D-glucopyranoside, α and β tocopherol, a mixture of lupeol, α and β-amyrin, sitosterol and a mixture of glucoside flavonoids (CP-13). The structures of these compounds were identified by 1 H and 13 C NMR spectral analysis and comparison with literature data. Absolute configuration of the catechin was determinate by circular dichroism. Antioxidant activity (EC 50 ), evaluated by 2,2-diphenyl-1-picrylhidrazyl (DPPH) assay system, decreased in the order: (+)-catechin > hydroalcoholic fraction > CP-13 > aqueous fraction > EtOH extract. (author)

  14. Plant-derived cannabinoids modulate the activity of transient receptor potential channels of ankyrin type-1 and melastatin type-8.

    Science.gov (United States)

    De Petrocellis, Luciano; Vellani, Vittorio; Schiano-Moriello, Aniello; Marini, Pietro; Magherini, Pier Cosimo; Orlando, Pierangelo; Di Marzo, Vincenzo

    2008-06-01

    The plant cannabinoids (phytocannabinoids), cannabidiol (CBD), and Delta(9)-tetrahydrocannabinol (THC) were previously shown to activate transient receptor potential channels of both vanilloid type 1 (TRPV1) and ankyrin type 1 (TRPA1), respectively. Furthermore, the endocannabinoid anandamide is known to activate TRPV1 and was recently found to antagonize the menthol- and icilin-sensitive transient receptor potential channels of melastatin type 8 (TRPM8). In this study, we investigated the effects of six phytocannabinoids [i.e., CBD, THC, CBD acid, THC acid, cannabichromene (CBC), and cannabigerol (CBG)] on TRPA1- and TRPM8-mediated increase in intracellular Ca2+ in either HEK-293 cells overexpressing the two channels or rat dorsal root ganglia (DRG) sensory neurons. All of the compounds tested induced TRPA1-mediated Ca2+ elevation in HEK-293 cells with efficacy comparable with that of mustard oil isothiocyanates (MO), the most potent being CBC (EC(50) = 60 nM) and the least potent being CBG and CBD acid (EC(50) = 3.4-12.0 microM). CBC also activated MO-sensitive DRG neurons, although with lower potency (EC(50) = 34.3 microM). Furthermore, although none of the compounds tested activated TRPM8-mediated Ca2+ elevation in HEK-293 cells, they all, with the exception of CBC, antagonized this response when it was induced by either menthol or icilin. CBD, CBG, THC, and THC acid were equipotent (IC(50) = 70-160 nM), whereas CBD acid was the least potent compound (IC(50) = 0.9-1.6 microM). CBG inhibited Ca2+ elevation also in icilin-sensitive DRG neurons with potency (IC(50) = 4.5 microM) similar to that of anandamide (IC(50) = 10 microM). Our findings suggest that phytocannabinoids and cannabis extracts exert some of their pharmacological actions also by interacting with TRPA1 and TRPM8 channels, with potential implications for the treatment of pain and cancer.

  15. Discovery, synthesis, and structure-activity relationships of 20(S)-protopanaxadiol (PPD) derivatives as a novel class of AMPKα2β1γ1 activators.

    Science.gov (United States)

    Liu, Junhua; Chen, Dakai; Liu, Peng; He, Mengna; Li, Jia; Li, Jingya; Hu, Lihong

    2014-05-22

    Adenosine 5'-monophosphate-activated protein kinase (AMPK) has been demonstrated as a promising drug target due to its regulatory function in glucose and lipid metabolism. 20(S)-protopanoxadiol (PPD) was firstly identified from high throughput screening as a small molecule activator of AMPK subtype α2β1γ1. In order to enhance its potency on AMPK, a series of PPD derivatives were synthesized and evaluated. Structure-activity relationship study showed that the amine derivatives at the 24-position (groups I-VI) can improve the potency (EC50: 0.7-2.3 μM) and efficacy (fold: 2.5-3.8). Among them, compounds 12 and 13 exhibited the best potency (EC50: 1.2 and 0.7 μM) and efficacy (fold: 3.7 and 3.8). Further study suggested the mechanism of AMPK activation may functioned at the allosteric position, resulting the inhibition of the lipid synthesis in HepG2 cell model. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  16. Chemical constituents of the essential oil, antioxidant and antibacterial activities from Elettariopsis curtisii Baker.

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    Vanida Chairgulprasert

    2008-08-01

    Full Text Available Elettariopsis curtisii Baker, the culinary and medicinal herb, was investigated to elucidate its chemical constituents and determine antioxidant and antibacterial activities. The essential oil of E. curtisii was obtained by steam distillation of fresh rhizomes in a maximum yield of 0.63%. GC-MS data indicated the presence of six compounds, of which trans-2-decenal (78.03% was the principal constituent. The essential oils and also the hexane, dichloromethane and methanol extracts from the rhizomes and leaves were assessed for antioxidant and antibacterial activities. In an evaluation of antioxidant activity, the crude dichloromethane extract of the leaves exhibited the highest scavenging effect on the DPPH radicalwith an EC50 of 0.28+0.01 mg/mL. The leaf dichloromethane extract also had the highest total phenol concentration, (73.4+2.80 mg GA/g of extract whereas the crude methanol extract from the rhizomes had the highest reducing power with an EC50 of 2.07+0.06 mg/mL. In terms of antibacterial activity, the essential oil (distilled from either the leaves or the rhizomesdisplayed the highest inhibitory activity, with the same MID value of 1 mg/disc against 5 strains of bacteria, Bacillus subtilis,Escherichia coli, Staphylococcus aureus, Sarcina sp. and Pseudomonas aeruginosa.

  17. The traditional use of Vachellia nilotica for sexually transmitted diseases is substantiated by the antiviral activity of its bark extract against sexually transmitted viruses.

    Science.gov (United States)

    Donalisio, Manuela; Cagno, Valeria; Civra, Andrea; Gibellini, Davide; Musumeci, Giuseppina; Rittà, Massimo; Ghosh, Manik; Lembo, David

    2018-03-01

    Vachellia (Acacia) nilotica and other plants of this genus have been used in traditional medicine of Asian and African countries to treat many disorders, including sexually transmitted diseases, but few studies were performed to validate their anti-microbial and anti-viral activity against sexually transmitted infections. The present study was undertaken to explore whether the ethnomedical use of V.nilotica to treat genital lesions is substantiated by its antiviral activity against the human immunodeficiency virus (HIV), the herpes simplex virus (HSV) and the human papillomavirus (HPV). The antiviral activity of V.nilotica was tested in vitro by virus-specific inhibition assays using HSV-2 strains, sensible or resistant to acyclovir, HIV-1IIIb strain and HPV-16 pseudovirion (PsV). The potential mode of action of extract against HSV-2 and HPV-16 was further investigated by virus inactivation and time-of-addition assays on cell cultures. V.nilotica chloroform, methanolic and water bark extracts exerted antiviral activity against HSV-2 and HPV-16 PsV infections; among these, methanolic extract showed the best EC50s with values of 4.71 and 1.80µg/ml against HSV-2 and HPV-16, respectively, and it was also active against an acyclovir-resistant HSV-2 strain with an EC50 of 6.71µg/ml. By contrast, no suppression of HIV infection was observed. Investigation of the mechanism of action revealed that the methanolic extract directly inactivated the infectivity of the HPV-16 particles, whereas a partial virus inactivation and interference with virus attachment (EC50 of 2.74µg/ml) were both found to contribute to the anti-HSV-2 activity. These results support the traditional use of V.nilotica applied externally for the treatment of genital lesions. Further work remains to be done in order to identify the bioactive components. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Anticancer activity of botanical alkyl hydroquinones attributed to topoisomerase II poisoning

    International Nuclear Information System (INIS)

    Huang, C.-P.; Fang, W.-H.; Lin, L.-I.; Chiou, Robin Y.; Kan, L.-S.; Chi, N.-H.; Chen, Y.-R.; Lin, T.-Y.; Lin, S.-B.

    2008-01-01

    Cytotoxic alkyl hydroquinone compounds have been isolated from many plants. We previously isolated 3 structurally similar cytotoxic alkyl hydroquinone compounds from the sap of the lacquer tree Rhus succedanea L. belonging to the sumac family, which have a long history of medicinal use in Asia. Each has an unsaturated alkyl chain attached to the 2-position of a hydroquinone ring. One of these isolates, 10'(Z),13'(E),15'(E)-heptadecatrienylhydroquinone [HQ17(3)], being the most cytotoxic, was chosen for studying the anticancer mechanism of these compounds. We found that HQ17(3) was a topoisomerase (Topo) II poison. It irreversibly inhibited Topo IIα activity through the accumulation of Topo II-DNA cleavable complexes. A cell-based assay showed that HQ17(3) inhibited the growth of leukemia HL-60 cells with an EC 50 of 0.9 μM, inhibited the topoisomerase-II-deficient cells HL-60/MX2 with an EC 50 of 9.6 μM, and exerted no effect on peripheral blood mononuclear cells at concentrations up to 50 μM. These results suggest that Topo II is the cellular drug target. In HL-60 cells, HQ17(3) promptly inhibited DNA synthesis, induced chromosomal breakage, and led to cell death with an EC 50 about one-tenth that of hydroquinone. Pretreatment of the cells with N-acetylcysteine could not attenuate the cytotoxicity and DNA damage induced by HQ17(3). However, N-acetylcysteine did significantly reduce the cytotoxicity of hydroquinone. In F344 rats, intraperitoneal injection of HQ17(3) for 28 days induced no clinical signs of toxicity. These results indicated that HQ17(3) is a potential anticancer agent, and its structural features could be a model for anticancer drug design

  19. Bioactive Peptides from Cartilage Protein Hydrolysate of Spotless Smoothhound and Their Antioxidant Activity In Vitro

    Directory of Open Access Journals (Sweden)

    Jing Tao

    2018-03-01

    Full Text Available In the experiment, crude proteins from spotless smoothhound (Mustelus griseus, cartilages were isolated by HCl-Guanidine buffer, and its hydrolysate was prepared using trypsin at pH 8.0, 40 °C with a total enzyme dose of 2.5%. Subsequently, three antioxidant peptides were purified from the hydrolysate using membrane ultrafiltration, anion-exchange chromatography, gel filtration chromatography, and reverse phase high-performance liquid chromatography. The amino acid sequences of isolated peptides were identified as Gly-Ala-Glu-Arg-Pro (MCPE-A; Gly-Glu-Arg-Glu-Ala-Asn-Val-Met (MCPE-B; and Ala-Glu-Val-Gly (MCPE-C with molecular weights of 528.57, 905.00, and 374.40 Da, respectively, using protein amino acid sequence analyzer and mass spectrum. MCPE-A, MCPE-B and MCPE-C exhibited good scavenging activities on 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH• (EC50 3.73, 1.87, and 2.30 mg/mL, respectively, hydroxyl radicals (HO• (EC50 0.25, 0.34, and 0.06 mg/mL, respectively, 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radicals (ABTS+• (EC50 0.10, 0.05, and 0.07 mg/mL, respectively and superoxide anion radicals ( O 2 − • (EC50 0.09, 0.33, and 0.18 mg/mL, respectively. MCPE-B showed similar inhibiting ability on lipid peroxidation with butylated hydroxytoluene (BHT in a linoleic acid model system. Furthermore, MCPE-A, MCPE-B, and MCPE-C could protect H2O2-induced HepG2 cells from oxidative stress by decreasing the content of malonaldehyde (MDA and increasing the levels of superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GSH-Px, and glutathione reductase (GSH-Rx. Glu, Gly, Met, and Pro in their sequences and low molecular weight could be attributed to the antioxidant activities of three isolated peptides. These results suggested that GAERP (MCPE-A, GEREANVM (MCPE-B, and AEVG (MCPE-C from cartilage protein hydrolysate of spotless smoothhound might serve as potential antioxidants and be used in the pharmaceutical and

  20. Activity of andrographolide against chikungunya virus infection.

    Science.gov (United States)

    Wintachai, Phitchayapak; Kaur, Parveen; Lee, Regina Ching Hua; Ramphan, Suwipa; Kuadkitkan, Atichat; Wikan, Nitwara; Ubol, Sukathida; Roytrakul, Sittiruk; Chu, Justin Jang Hann; Smith, Duncan R

    2015-09-18

    Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that has recently engendered large epidemics around the world. There is no specific antiviral for treatment of patients infected with CHIKV, and development of compounds with significant anti-CHIKV activity that can be further developed to a practical therapy is urgently required. Andrographolide is derived from Andrographis paniculata, a herb traditionally used to treat a number of conditions including infections. This study sought to determine the potential of andrographolide as an inhibitor of CHIKV infection. Andrographolide showed good inhibition of CHIKV infection and reduced virus production by approximately 3log10 with a 50% effective concentration (EC50) of 77 μM without cytotoxicity. Time-of-addition and RNA transfection studies showed that andrographolide affected CHIKV replication and the activity of andrographolide was shown to be cell type independent. This study suggests that andrographolide has the potential to be developed further as an anti-CHIKV therapeutic agent.

  1. Structural characterization and evaluation of antioxidant, anticancer and hypoglycemic activity of radiation degraded oat (Avena sativa) β- glucan

    Science.gov (United States)

    Hussain, Peerzada R.; Rather, Sarver A.; Suradkar, Prashant P.

    2018-03-01

    Oat β-D-glucan after extraction was degraded at doses of 3, 6, 9, 12 and 15 kGy. The average molecular weight decreased to 45 kDa at dose of 15 kGy from an initial value of 200 kDa in native sample. XRD analysis revealed no significant change in diffraction pattern of irradiated samples when compared with control, except a decrease in intensity of x-ray diffraction. The results of the antioxidant activity revealed decrease in EC50 values and corresponding increase in antioxidant activity of radiation degraded oat β-D-glucan. Results of the anticancer studies indicated that cytotoxicity of gamma irradiated oat β-D-glucan in cancer cell lines was highest against colo-205 and MCF7 cancer cells compared to T47D cell and no cytotoxicity was observed in normal cell lines at all concentrations used. Evaluation of hypoglycemic activity showed highest inhibition in α-glucosidase activity compared to α-amylase activity due to gamma irradiation of oat β-D-glucan. Comparison of the EC50 values of known standards and gamma irradiated oat beta-glucan samples indicates that radiation treatment significantly modified the biological activity of the beta-glucan samples. Therefore, it is suggested that gamma irradiation can be used for producing low molecular weight oat β-D-glucan; which can help in modifying the biological activities.

  2. Phytochemical screening, antiglycation and antioxidant activities of whole plant of Boerhavia repens L. from Cholistan, Pakistan.

    Science.gov (United States)

    Nazneen, Fariha; Sheikh, Munir A; Jameel, Amir; Rahman, Ziaur

    2016-05-01

    Present study was aimed to explore a traditionally used indigenous medicinal plant Boerhavia repens (Nyctaginaceae family) of the Cholistan desert, Pakistan. Crude aqueous and methanolic extracts of the whole plant were investigated in vitro for preliminary phytochemical screening, antioxidant and antiglycation activities. Antioxidant activities were determined by total phenolic contents, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and inhibition of lipid peroxidation. For antiglycation activities browning production was noted and thiobarbituric acid (TBA) technique was used to determine glycation level. Boerhavia repens expressed considerable amounts of phytochemicals. Extract yield was found to be 4.59%-7.85% g/100g of dry matter with total phenolics ranging from 47.9- 190.77mg/GAE per g for aqueous and methanol extract respectively. Strong inhibitory effect was exhibited by methanolic extract in linoleic acid per oxidation system (86.11%, EC50=0.99mg/mL) and DPPH assay (88.65%, EC50=212.33μg/ml). In term of browning maximum inhibition (81.50%) was exhibited by methanolic extract at 37°C at third week of incubation. Both extracts expressed significant (P>0.05) and comparable inhibition of glycation level. In conclusion, Boerhavia repens showed promising antioxidant and antiglycation activities validating its therapeutic potential.

  3. Α-amino-β-fluorocyclopropanecarboxylic acids as a new tool for drug development: synthesis of glutamic acid analogs and agonist activity towards metabotropic glutamate receptor 4.

    Science.gov (United States)

    Lemonnier, Gérald; Lion, Cédric; Quirion, Jean-Charles; Pin, Jean-Philippe; Goudet, Cyril; Jubault, Philippe

    2012-08-01

    Herein we describe the diastereoselective synthesis of glutamic acid analogs and the evaluation of their agonist activity towards metabotropic glutamate receptor subtype 4 (mGluR4). These analogs are based on a monofluorinated cyclopropane core substituted with an α-aminoacid function. The potential of this new building block as a tool for the development of a novel class of drugs is demonstrated with racemic analog 11a that displayed the best agonist activity with an EC50 of 340 nM. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. The effect of glycine replacement with flexible ω-amino acids on the antimicrobial and haemolytic activity of an amphipathic cyclic heptapeptide

    DEFF Research Database (Denmark)

    Oddo, Alberto; Nyberg, Nils; Frimodt-Møller, Niels

    2015-01-01

    residue with a variety of flexible residues (i.e. ω-amino and α,ω-diamino acids). The resulting library has been tested for antimicrobial activity against a wide range of clinically relevant pathogens as well as for toxicity to red blood cells. Circular dichroism and molecular modelling have been used...... to study changes in conformation. Increments as high as 16-fold in antimicrobial activity (as effective as lipidation) and >2-fold in haemolytic EC50 values were observed. Interestingly, secondary structures can be stabilized by increasing, rather than decreasing, ring flexibility....

  5. Discovery and structure-activity relationships of (2-(arylthio)benzylideneamino)guanidines as a novel series of potent apoptosis inducers.

    Science.gov (United States)

    Zhang, Han-Zhong; Crogan-Grundy, Candace; May, Chris; Drewe, John; Tseng, Ben; Cai, Sui Xiong

    2009-04-01

    1-(2-(2,5-Dimethoxyphenylthio)benzylidene)semicarbazide (2a) was discovered as a potent apoptosis inducer through our cell based HTS assay. SAR study led to the discovery of a more aqueous soluble analog (2-(2,5-dimethoxyphenylthio)-6-methoxybenzylideneamino)guanidine (5e) with EC(50) value of 60 nM in the caspase activation assay and GI(50) value of 62 nM in the growth inhibition assay in T47D cells. Compound 5e was found to be an inhibitor of tubulin polymerization and efficacious in a MX-1 breast tumor model.

  6. [Photometric micro-titration model of DPPH radicals scavenging activity and its application].

    Science.gov (United States)

    Gao, Yun-tao; Wei, Wei; Ye, Li-qing; Li, Xiao-fen; Liu, Ping; Zhang, Hong-jiao; Yang, Lu; Yu, Jiao-jiao; Cha, Jia-wei

    2015-02-01

    In the present paper, the stoichiometric ratio (R) for the interreaction of DPPH radicals with the antoxidant was employed as a evaluation index for DPPH radicals scavenging activity of antioxidants. This evaluation index was related only with the stoichiometric relationship between DPPH radicals and the antioxidant, not the relationship with the initial DPPH amount and the volume of sample, which could offer a solution for the problem of poor comparability of EC50 under different conditions. A novel photometric micro-titration method was proposed for the determination of the stoichiometric ratio (R) for the interreaction of DPPH radicals with the antoxidant. The titration equation was established based on the absorbance difference (deltaA) of DPPH radicals in the titration process and the added amount of antoxidant. The stoichiometric ratio (R) for the reaction of DPPH radicals with the addition amount of antoxidant was determined by the titration equation obtained, while, the DPPH median elimination concentration (EC50) of antoxidant can be calculated by the stoichiometric ratio (R). The above photometric micro-titration model was verified using rutin as DPPH radicals scavenger. As experiment results, the stoichiometric ratio (R) of DPPH radicals to rutin was determined to be in the range of 1.817-1.846. The calculated value of EC50 was 1.196 x 10(-3), 2.392 x 10(-3), 4.819 x 10(-3) and 7.292 x 10(-3) mg x mL(-1) for 1.12 x 10(-7), 2.24 x 10(-7), 4.48 x 10(-7) and 6.72 x 10(-7) mol of the additon amount of DPPH radicals, respectively. The proposed method has better precision and reliability with smaller amount of sample than conventional method. While, the obtained stoichiometric ratio value (R) of rutin was employed to calculate the rutin median elimination concentration for DPPH EC50) according to the conditions as reported in the literatures, and the calculated results were consistent with that reported in the literatures.

  7. Acute toxicity, brine shrimp cytotoxicity and relaxant activity of fruits of callistemon citrinus curtis

    Directory of Open Access Journals (Sweden)

    Shah Ismail

    2011-10-01

    Full Text Available Abstract Background Callistemon citrinus Curtis belongs to family Myrtaceae that has a great medicinal importance. In our previous work, fruits of Callistemon citrinus were reported to have relaxant (antispasmodic activity. The current work describes the screening of fractions of the crude methanol extract for tracing spasmolytic constituents so that it shall help us for isolation of bioactive compounds. Acute toxicity and brine shrimp cytotoxicity of crude methanol extract are also performed to standardize it. Methods The crude methanol extract was obtained by maceration with distilled water (500 ml three times and fractionated successively with n-hexane, chloroform, ethyl acetate and n-butanol (300 ml of each solvent. Phytochemical analysis for crude methanol extract was performed. Acute toxicity studies were performed in mice. Brine shrimp cytotoxicity studies were performed to determine its cytotoxicity and standardize it. In other series of experiments, rabbits' jejunum preparations were used in screening for possible relaxant activities of various fractions. They were applied in concentrations of 0.01, 0.03, 0.1, 0.3, 1.0, 3.0, 5.0 and 10.0 mg/ml on spontaneous rabbits' jejunum preparations. In similar fashion, fractions were also tested on KCl (80 mM -induced contractions. Calcium chloride curves were constructed in K-rich Tyrode's solution. The effects of various fractions were tested on calcium chloride curves at concentrations 1.0, 3.0, 5.0 and 10.0 mg/ml. Curves of verapamil used as reference drug at concentration 0.1 μM and 0.3 μM were also constructed. The curves were compared with their respective controls for possible right shift. Results Methanol extract tested strongly positive for saponins and tannins. However, it tested mild positive for presence of proteins, amino acids, carbohydrates and phenolic compounds. LD50 value for crude methanol extract is 476.25 ± 10.3 (470-481, n = 4 mg/ml. Similarly, EC50 value for brine shrimp

  8. Indoline Amide Glucosides from Portulaca oleracea: Isolation, Structure, and DPPH Radical Scavenging Activity.

    Science.gov (United States)

    Jiao, Ze-Zhao; Yue, Su; Sun, Hong-Xiang; Jin, Tian-Yun; Wang, Hai-Na; Zhu, Rong-Xiu; Xiang, Lan

    2015-11-25

    A polyamide column chromatography method using an aqueous ammonia mobile phase was developed for large-scale accumulation of water-soluble indoline amide glucosides from a medicinal plant, Portulaca oleracea. Ten new [oleraceins H, I, K, L, N, O, P, Q, R, S (1-10)] and four known [oleraceins A-D (11-14)] indoline amide glucosides were further purified and structurally characterized by various chromatographic and spectroscopic methods. The DPPH radical scavenging activities of oleraceins K (5) and L (6), with EC50 values of 15.30 and 16.13 μM, respectively, were twice that of a natural antioxidant, vitamin C; the EC50 values of the 12 other indoline amides, which ranged from 29.05 to 43.52 μM, were similar to that of vitamin C. Structure-activity relationships indicated that the DPPH radical scavenging activities of these indoline amides correlate with the numbers and positions of the phenolic hydroxy groups.

  9. Antioxidant and DNA Damage Protecting Activity of Exopolysaccharides from the Endophytic Bacterium Bacillus cereus SZ1

    Directory of Open Access Journals (Sweden)

    Li Ping Zheng

    2016-02-01

    Full Text Available An endophytic bacterium was isolated from the Chinese medicinal plant Artemisia annua L. The phylogenetic and physiological characterization indicated that the isolate, strain SZ-1, was Bacillus cereus. The endophyte could produce an exopolysaccharide (EPS at 46 mg/L. The 1,1-diphenyl-2-picrylhydracyl (DPPH radical scavenging activity of the EPS reached more than 50% at 3–5 mg/mL. The EPS was also effective in scavenging superoxide radical in a concentration dependent fashion with an EC50 value of 2.6 mg/mL. The corresponding EC50 for scavenging hydroxyl radical was 3.1 mg/mL. Moreover, phenanthroline-copper complex-mediated chemiluminescent emission of DNA damage was both inhibited and delayed by EPS. The EPS at 0.7–1.7 mg/mL also protected supercoiled DNA strands in plasmid pBR322 against scission induced by Fenton-mediated hydroxyl radical. The preincubation of PC12 cells with the EPS prior to H2O2 exposure increased the cell survival and glutathione (GSH level and catalase (CAT activities, and decreased the level of malondialdehyde (MDA and lactate dehydrogenase (LDH activity in a dose-dependent manner, suggesting a pronounced protective effect against H2O2-induced cytotoxicity. Our study indicated that the EPS could be useful for preventing oxidative DNA damage and cellular oxidation in pharmaceutical and food industries.

  10. Antimalarial activity of abietane ferruginol analogues possessing a phthalimide group.

    Science.gov (United States)

    González, Miguel A; Clark, Julie; Connelly, Michele; Rivas, Fatima

    2014-11-15

    The abietane-type diterpenoid (+)-ferruginol, a bioactive compound isolated from New Zealand's Miro tree (Podocarpus ferruginea), displays relevant pharmacological properties, including antimicrobial, cardioprotective, anti-oxidative, anti-plasmodial, leishmanicidal, anti-ulcerogenic, anti-inflammatory and anticancer. Herein, we demonstrate that ferruginol (1) and some phthalimide containing analogues 2-12 have potential antimalarial activity. The compounds were evaluated against malaria strains 3D7 and K1, and cytotoxicity was measured against a mammalian cell line panel. A promising lead, compound 3, showed potent activity with an EC50 = 86 nM (3D7 strain), 201 nM (K1 strain) and low cytotoxicity in mammalian cells (SI>290). Some structure-activity relationships have been identified for the antimalarial activity in these abietane analogues. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Phytochemistry, cytotoxicity and antiviral activity of Eleusine indica (sambau)

    Science.gov (United States)

    Iberahim, Rashidah; Yaacob, Wan Ahmad; Ibrahim, Nazlina

    2015-09-01

    Goose grass also known as Eleusine indica (EI) is a local medicinal plant that displays antioxidant, antimicrobial and anticancer activities. The present study is to determine the phytochemical constituents, cytotoxicity and antiviral activities for both crude extract and fraction obtained from the plant. The crude extract contained more secondary metabolites compared to the hexane fraction as gauged using standard phytochemical tests. Cytotoxicity screening against Vero cells using MTT assay showed that the CC50 values for crude extract and hexane fraction were 2.07 and 5.62 mg/ml respectively. The antiviral activity towards Herpes Simplex Virus type 1 (HSV-1) was determined using plaque reduction assay. The selective indices (SI = CC50 / EC50) for both methanol extract and hexane fraction were 12.2 and 6.2 respectively. These results demonstrate that the extract prepared from E. indica possesses phytochemical compound that was non cytotoxic to the cell with potential antiviral activity.

  12. Antioxidant Activity of Mulberry Fruit Extracts

    Science.gov (United States)

    Arfan, Muhammad; Khan, Rasool; Rybarczyk, Anna; Amarowicz, Ryszard

    2012-01-01

    Phenolic compounds were extracted from the fruits of Morus nigra and Morus alba using methanol and acetone. The sugar-free extracts (SFEs) were prepared using Amberlite XAD-16 column chromatography. All of the SFEs exhibited antioxidant potential as determined by ABTS (0.75–1.25 mmol Trolox/g), DPPH (2,2-diphenyl-1-picrylhydrazyl) (EC50 from 48 μg/mL to 79 μg/mL), and reducing power assays. However, a stronger activity was noted for the SFEs obtained from Morus nigra fruits. These extracts also possessed the highest contents of total phenolics: 164 mg/g (methanolic SFE) and 173 mg/g (acetonic SFE). The presence of phenolic acids and flavonoids in the extracts was confirmed using HPLC method and chlorogenic acid and rutin were found as the dominant phenolic constituents in the SFEs. PMID:22408465

  13. Antioxidant Activity of Mulberry Fruit Extracts

    Directory of Open Access Journals (Sweden)

    Ryszard Amarowicz

    2012-02-01

    Full Text Available Phenolic compounds were extracted from the fruits of Morus nigra and Morus alba using methanol and acetone. The sugar-free extracts (SFEs were prepared using Amberlite XAD-16 column chromatography. All of the SFEs exhibited antioxidant potential as determined by ABTS (0.75–1.25 mmol Trolox/g, DPPH (2,2-diphenyl-1-picrylhydrazyl (EC50 from 48 μg/mL to 79 μg/mL, and reducing power assays. However, a stronger activity was noted for the SFEs obtained from Morus nigra fruits. These extracts also possessed the highest contents of total phenolics: 164 mg/g (methanolic SFE and 173 mg/g (acetonic SFE. The presence of phenolic acids and flavonoids in the extracts was confirmed using HPLC method and chlorogenic acid and rutin were found as the dominant phenolic constituents in the SFEs.

  14. Antifouling Activity towards Mussel by Small-Molecule Compounds from a Strain of Vibrio alginolyticus Bacterium Associated with Sea Anemone Haliplanella sp.

    Science.gov (United States)

    Wang, Xiang; Huang, Yanqiu; Sheng, Yanqing; Su, Pei; Qiu, Yan; Ke, Caihuan; Feng, Danqing

    2017-03-28

    Mussels are major fouling organisms causing serious technical and economic problems. In this study, antifouling activity towards mussel was found in three compounds isolated from a marine bacterium associated with the sea anemone Haliplanella sp. This bacterial strain, called PE2, was identified as Vibrio alginolyticus using morphology, biochemical tests, and phylogenetic analysis based on sequences of 16S rRNA and four housekeeping genes ( rpoD, gyrB, rctB, and toxR ). Three small-molecule compounds (indole, 3-formylindole, and cyclo (Pro-Leu)) were purified from the ethyl acetate extract of V. alginolyticus PE2 using column chromatography techniques. They all significantly inhibited byssal thread production of the green mussel Perna viridis , with EC 50 values of 24.45 μg/ml for indole, 50.07 μg/ml for 3-formylindole, and 49.24 μg/ml for cyclo (Pro-Leu). Previous research on the antifouling activity of metabolites from marine bacteria towards mussels is scarce. Indole, 3-formylindole and cyclo (Pro-Leu) also exhibited antifouling activity against settlement of the barnacle Balanus albicostatus (EC 50 values of 8.84, 0.43, and 11.35 μg/ml, respectively) and the marine bacterium Pseudomonas sp. (EC 50 values of 42.68, 69.68, and 39.05 μg/ml, respectively). These results suggested that the three compounds are potentially useful for environmentally friendly mussel control and/or the development of new antifouling additives that are effective against several biofoulers.

  15. Anti-oxidative and antimicrobial activities of Hieracium pilosella L. extracts

    Directory of Open Access Journals (Sweden)

    LJILJANA P. STANOJEVIC

    2008-05-01

    Full Text Available The anti-oxidative and antimicrobial activities of different extracts from Hieracium pilosella L. (Asteraceae whole plant were investigated. The total dry extracts were determined for all the investigated solvents: methanol, dichloromethane, ethyl acetate and dichloromethane:methanol (9:1. It was found that the highest yield was obtained by extraction with methanol (12.9 g/100 g of dry plant material. Qualitative and quantitative analysis were performed by the HPLC method, using external standards. Chlorogenic acid, apigenin-7-O-glucoside and umbelliferone were detected in the highest quantity in the extracts. The qualitative and quantitative composition of the extracts depends on the solvent used. The 1,1-diphenyl-2-picrylhydrazyl (DPPH radical scavenging effect of the extracts was determined spectrophotometrically. The highest radical scavenging effect was observed in the methanolic extract, both with and without incubation, EC50 = 0.012 and EC50 = 0.015 mg ml-1, respectively. The antimicrobial activities of the extracts towards the bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Salmonella enteritidis and Klebsiella pneumoniae and the fungi (Aspergillus niger and Candida albicans were determined by the disc diffusion method. The minimal inhibitory concentrations were determined for all the investigated extracts against all the mentioned microorganisms.

  16. FVIIa-sTF and Thrombin Inhibitory Activities of Compounds Isolated from Microcystis aeruginosa K-139

    Directory of Open Access Journals (Sweden)

    Andrea Roxanne J. Anas

    2017-08-01

    Full Text Available The rise of bleeding and bleeding complications caused by oral anticoagulant use are serious problems nowadays. Strategies that block the initiation step in blood coagulation involving activated factor VII-tissue factor (fVIIa-TF have been considered. This study explores toxic Microcystis aeruginosa K-139, from Lake Kasumigaura, Ibaraki, Japan, as a promising cyanobacterium for isolation of fVIIa-sTF inhibitors. M. aeruginosa K-139 underwent reversed-phase solid-phase extraction (ODS-SPE from 20% MeOH to MeOH elution with 40%-MeOH increments, which afforded aeruginosin K-139 in the 60% MeOH fraction; micropeptin K-139 and microviridin B in the MeOH fraction. Aeruginosin K-139 displayed an fVIIa-sTF inhibitory activity of ~166 µM, within a 95% confidence interval. Micropeptin K-139 inhibited fVIIa-sTF with EC50 10.62 µM, which was more efficient than thrombin inhibition of EC50 26.94 µM. The thrombin/fVIIa-sTF ratio of 2.54 in micropeptin K-139 is higher than those in 4-amidinophenylmethane sulfonyl fluoride (APMSF and leupeptin, when used as positive controls. This study proves that M. aeruginosa K-139 is a new source of fVIIa-sTF inhibitors. It also opens a new avenue for micropeptin K-139 and related depsipeptides as fVIIa-sTF inhibitors.

  17. Activation of peripheral blood mononuclear cells by dengue virus infection depotentiates balapiravir.

    Science.gov (United States)

    Chen, Yen-Liang; Abdul Ghafar, Nahdiyah; Karuna, Ratna; Fu, Yilong; Lim, Siew Pheng; Schul, Wouter; Gu, Feng; Herve, Maxime; Yokohama, Fumiaki; Wang, Gang; Cerny, Daniela; Fink, Katja; Blasco, Francesca; Shi, Pei-Yong

    2014-02-01

    In a recent clinical trial, balapiravir, a prodrug of a cytidine analog (R1479), failed to achieve efficacy (reducing viremia after treatment) in dengue patients, although the plasma trough concentration of R1479 remained above the 50% effective concentration (EC(50)). Here, we report experimental evidence to explain the discrepancy between the in vitro and in vivo results and its implication for drug development. R1479 lost its potency by 125-fold when balapiravir was used to treat primary human peripheral blood mononuclear cells (PBMCs; one of the major cells targeted for viral replication) that were preinfected with dengue virus. The elevated EC(50) was greater than the plasma trough concentration of R1479 observed in dengue patients treated with balapiravir and could possibly explain the efficacy failure. Mechanistically, dengue virus infection triggered PBMCs to generate cytokines, which decreased their efficiency of conversion of R1479 to its triphosphate form (the active antiviral ingredient), resulting in decreased antiviral potency. In contrast to the cytidine-based compound R1479, the potency of an adenosine-based inhibitor of dengue virus (NITD008) was much less affected. Taken together, our results demonstrate that viral infection in patients before treatment could significantly affect the conversion of the prodrug to its active form; such an effect should be calculated when estimating the dose efficacious for humans.

  18. Ovicidal and larvicidal activity of extracts of Opuntia ficus-indica against gastrointestinal nematodes of naturally infected sheep.

    Science.gov (United States)

    Féboli, Aline; Laurentiz, Antonio C; Soares, Suelen C S; Augusto, Jeferson G; Anjos, Luciano A; Magalhães, Lizandra G; Filardi, Rosemeire S; Laurentiz, Rosangela S

    2016-08-15

    This study describes the in vitro anthelmintic activity of extracts from Opuntia ficus indica against gastrointestinal nematodes of sheep. The anthelmintic activity was evaluated by inhibition of egg hatching, larval development and larval migration assays. The residual aqueous fractions from cladodes and fruits showed higher ovicidal activity with EC50 values of 7.2mg/mL and 1.5mg/mL, respectively. The aqueous, hexane, and ethyl acetate fractions from fruits and the aqueous fraction from cladodes inhibited 100% of larval development at the lowest concentration tested (1.56mg/mL). The crude cladode and fruit ethanolic extracts inhibited larval migration and showed EC50 values of 0.74mg/mL and 0.27mg/mL, respectively. Phytochemical screening detected high concentrations of alkaloids, tannins, flavonoids, and saponins in the fruits and cladodes. The results demonstrated that O. ficus exhibits anthelmintic activity in vitro, suggesting that, beyond its nutritional potential, this plant can also be an ally for parasite control in sheep. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Functional characterization of the 1,5-benzodiazepine clobazam and its major active metabolite N-desmethylclobazam at human GABAA receptors expressed in Xenopus laevis oocytes

    DEFF Research Database (Denmark)

    Hammer, Harriet; Ebert, Bjarke; Jensen, Henrik S.

    2015-01-01

    different in vivo adverse effects and addiction liability profile than the classic 1,4-benzodiazepines. In this study, it was investigated whether the in vitro pharmacological properties of clobazam and its major active metabolite N-desmethylclobazam could explain some of these clinical differences...... by the 1,4-benzodiazepine clonazepam. All three compounds potentiated GABA EC20-evoked responses through the α1,2,3,5β2γ2S GABAARs in a reversible and concentration-dependent manner, with each displaying similar EC50 values at the four subtypes. Furthermore, the degrees of potentiation of the GABA EC20...

  20. Antiandrogenic activity of phthalate mixtures: Validity of concentration addition

    International Nuclear Information System (INIS)

    Christen, Verena; Crettaz, Pierre; Oberli-Schrämmli, Aurelia; Fent, Karl

    2012-01-01

    Phthalates and bisphenol A have very widespread use leading to significant exposure of humans. They are suspected to interfere with the endocrine system, including the androgen, estrogen and the thyroid hormone system. Here we analyzed the antiandrogenic activity of six binary, and one ternary mixture of phthalates exhibiting complete antiandrogenic dose–response curves, and binary mixtures of phthalates and bisphenol A at equi-effective concentrations of EC 10 , EC 25 and EC 50 in MDA-kb2 cells. Mixture activity followed the concentration addition (CA) model with a tendency to synergism at high and antagonism at low concentrations. Isoboles and the toxic unit approach (TUA) confirmed the additive to synergistic activity of the binary mixtures BBP + DBP, DBP + DEP and DEP + BPA at high concentrations. Both methods indicate a tendency to antagonism for the EC 10 mixtures BBP + DBP, BBP + DEP and DBP + DEP, and the EC 25 mixture of DBP + BPA. A ternary mixture revealed synergism at the EC 50 , and weak antagonistic activity at the EC 25 level by the TUA. A mixture of five phthalates representing a human urine composition and reflecting exposure to corresponding parent compounds showed no antiandrogenic activity. Our study demonstrates that CA is an appropriate concept to account for mixture effects of antiandrogenic phthalates and bisphenol A. The interaction indicates a departure from additivity to antagonism at low concentrations, probably due to interaction with the androgen receptor and/or cofactors. This study emphasizes that a risk assessment of phthalates should account for mixture effects by applying the CA concept. -- Highlights: ► Antiandrogenic activity of mixtures of 2 and 3 phthalates are assessed in MDA-kb2 cells. ► Mixture activities followed the concentration addition model. ► A tendency to synergism at high and antagonism at low levels occurred.

  1. Antiviral activity of the EB peptide against zoonotic poxviruses

    Directory of Open Access Journals (Sweden)

    Altmann Sharon E

    2012-01-01

    Full Text Available Abstract Background The EB peptide is a 20-mer that was previously shown to have broad spectrum in vitro activity against several unrelated viruses, including highly pathogenic avian influenza, herpes simplex virus type I, and vaccinia, the prototypic orthopoxvirus. To expand on this work, we evaluated EB for in vitro activity against the zoonotic orthopoxviruses cowpox and monkeypox and for in vivo activity in mice against vaccinia and cowpox. Findings In yield reduction assays, EB had an EC50 of 26.7 μM against cowpox and 4.4 μM against monkeypox. The EC50 for plaque reduction was 26.3 μM against cowpox and 48.6 μM against monkeypox. A scrambled peptide had no inhibitory activity against either virus. EB inhibited cowpox in vitro by disrupting virus entry, as evidenced by a reduction of the release of virus cores into the cytoplasm. Monkeypox was also inhibited in vitro by EB, but at the attachment stage of infection. EB showed protective activity in mice infected intranasally with vaccinia when co-administered with the virus, but had no effect when administered prophylactically one day prior to infection or therapeutically one day post-infection. EB had no in vivo activity against cowpox in mice. Conclusions While EB did demonstrate some in vivo efficacy against vaccinia in mice, the limited conditions under which it was effective against vaccinia and lack of activity against cowpox suggest EB may be more useful for studying orthopoxvirus entry and attachment in vitro than as a therapeutic against orthopoxviruses in vivo.

  2. An analytical method for assessing stage-specific drug activity in Plasmodium vivax malaria: implications for ex vivo drug susceptibility testing.

    Directory of Open Access Journals (Sweden)

    Douglas H Kerlin

    Full Text Available The emergence of highly chloroquine (CQ resistant P. vivax in Southeast Asia has created an urgent need for an improved understanding of the mechanisms of drug resistance in these parasites, the development of robust tools for defining the spread of resistance, and the discovery of new antimalarial agents. The ex vivo Schizont Maturation Test (SMT, originally developed for the study of P. falciparum, has been modified for P. vivax. We retrospectively analysed the results from 760 parasite isolates assessed by the modified SMT to investigate the relationship between parasite growth dynamics and parasite susceptibility to antimalarial drugs. Previous observations of the stage-specific activity of CQ against P. vivax were confirmed, and shown to have profound consequences for interpretation of the assay. Using a nonlinear model we show increased duration of the assay and a higher proportion of ring stages in the initial blood sample were associated with decreased effective concentration (EC(50 values of CQ, and identify a threshold where these associations no longer hold. Thus, starting composition of parasites in the SMT and duration of the assay can have a profound effect on the calculated EC(50 for CQ. Our findings indicate that EC(50 values from assays with a duration less than 34 hours do not truly reflect the sensitivity of the parasite to CQ, nor an assay where the proportion of ring stage parasites at the start of the assay does not exceed 66%. Application of this threshold modelling approach suggests that similar issues may occur for susceptibility testing of amodiaquine and mefloquine. The statistical methodology which has been developed also provides a novel means of detecting stage-specific drug activity for new antimalarials.

  3. Reversible anti-settlement activity against Amphibalanus (= Balanus ) amphitrite, Bugula neritina , and Hydroides elegans by a nontoxic pharmaceutical compound, mizolastine

    KAUST Repository

    Zhou, Xiaojian

    2009-11-01

    Mizolastine, an antihistamine pharmaceutical, was found to significantly inhibit larval settlement of the barnacle Amphibalanus (=Balanus) amphitrite, the bryozoan Bugula neritina, and the polychaete Hydroides elegans with EC50 values of 4.2, 11.2, and 4.1 mg ml-1, respectively. No toxicity against the larvae of these three species was observed at the concentration range tested during incubations with mizolastine. To determine whether the anti-settlement activity of mizolastine is reversible, recovery bioassays using these three species were conducted. More than 70% of the larvae that had been exposed for 4 h to mizolastine at concentrations four-fold greater than their respective EC50 values completed normal metamorphosis. The results of the recovery bioassay provide evidence that the antisettlement effect of mizolastine is reversible in addition to being nontoxic. The anti-settlement activities of several intermediates of the synthesis process of mizolastine were also examined. One of the intermediates, 2-chloro-1-(4- fluorobenzyl)-1H-benzo[d]imidazole, inhibited larval settlement and metamorphosis with low toxicity. These results may improve the understanding of the key functional group responsible for the anti-settlement activity of mizolastine. © 2009 Taylor & Francis.

  4. In Vitro Cytotoxic, Antioxidant, and Antimicrobial Activities of Mesua beccariana (Baill. Kosterm., Mesua ferrea Linn., and Mesua congestiflora Extracts

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    Soek Sin Teh

    2013-01-01

    Full Text Available The in vitro cytotoxicity tests on the extracts of Mesua beccariana, M. ferrea, and M. congestiflora against Raji, SNU-1, HeLa, LS-174T, NCI-H23, SK-MEL-28, Hep-G2, IMR-32, and K562 were achieved using MTT assay. The methanol extracts of Mesua beccariana showed its potency towards the proliferation of B-lymphoma cell (Raji. In addition, only the nonpolar to semipolar extracts (hexane to ethyl acetate of the three Mesua species indicated cytotoxic effects on the tested panel of human cancer cell lines. Antioxidant assays were evaluated using DPPH scavenging radical assay and Folin-Ciocalteu method. The methanol extracts of M. beccariana and M. ferrea showed high antioxidant activities with low EC50 values of 12.70 and 9.77 μg/mL, respectively, which are comparable to that of ascorbic acid (EC50 = 5.62 μg/mL. Antibacterial tests were carried out using four Gram positive and four Gram negative bacteria on Mesua beccariana extracts. All the extracts showed negative results in the inhibition of Gram negative bacteria. Nevertheless, methanol extracts showed some activities against Gram positive bacteria which are Bacillus cereus, methicillin-sensitive Staphylococcus aureus (MSSA, and methicillin-resistant Staphylococcus aureus (MRSA, while the hexane extract also contributed some activities towards Bacillus cereus.

  5. Nematicidal activity of allylisothiocyanate from horseradish (Armoracia rusticana) roots against Meloidogyne incognita.

    Science.gov (United States)

    Aissani, Nadhem; Tedeschi, Paola; Maietti, Annalisa; Brandolini, Vincenzo; Garau, Vincenzo Luigi; Caboni, Pierluigi

    2013-05-22

    In recent years, there has been a great development in the search for new natural pesticides for crop protection aiming a partial or total replacement of currently used chemical nematicides. Glucosinolate breakdown products are volatile and are therefore good candidates for nematodes fumigants. In this article, the methanol-aqueous extract (1:1, w/v) of horseradish (Armoracia rusticana) fresh roots (MAH) was in vitro tested for nematicidal activity against second stage (J2) Meloidogyne incognita. The EC50 of MAH after 3 days of J2 immersion in test solutions was 251 ± 46 mg/L. The chemical composition analysis of the extract carried out by the GC-MS technique showed that allylisothicyanate was the most abundant compound. This pure compound induced J2 paralysis with an EC50 of 52.6 ± 45.6 and 6.6 ± 3.4 mg/L after 1 h and 3 days of incubation. The use of LC-MS/MS showed for the first time that horseradish root is rich in polyphenols. The study of isothiocyanate degradation in soil showed that allylisothiocyanate was the most quickly degradable compound (half-life <10 min), whereas no significant differences in half-life time were noted between degradation in regular and autoclaved soil.

  6. The cyanobacterial lectin scytovirin displays potent in vitro and in vivo activity against Zaire Ebola virus.

    Science.gov (United States)

    Garrison, Aura R; Giomarelli, Barbara G; Lear-Rooney, Calli M; Saucedo, Carrie J; Yellayi, Srikanth; Krumpe, Lauren R H; Rose, Maura; Paragas, Jason; Bray, Mike; Olinger, Gene G; McMahon, James B; Huggins, John; O'Keefe, Barry R

    2014-12-01

    The cyanobacterial lectin scytovirin (SVN) binds with high affinity to mannose-rich oligosaccharides on the envelope glycoprotein (GP) of a number of viruses, blocking entry into target cells. In this study, we assessed the ability of SVN to bind to the envelope GP of Zaire Ebola virus (ZEBOV) and inhibit its replication. SVN interacted specifically with the protein's mucin-rich domain. In cell culture, it inhibited ZEBOV replication with a 50% virus-inhibitory concentration (EC50) of 50 nM, and was also active against the Angola strain of the related Marburg virus (MARV), with a similar EC50. Injected subcutaneously in mice, SVN reached a peak plasma level of 100 nm in 45 min, but was cleared within 4h. When ZEBOV-infected mice were given 30 mg/kg/day of SVN by subcutaneous injection every 6h, beginning the day before virus challenge, 9 of 10 animals survived the infection, while all infected, untreated mice died. When treatment was begun one hour or one day after challenge, 70-90% of mice survived. Quantitation of infectious virus and viral RNA in samples of serum, liver and spleen collected on days 2 and 5 postinfection showed a trend toward lower titers in treated than control mice, with a significant decrease in liver titers on day 2. Our findings provide further evidence of the potential of natural lectins as therapeutic agents for viral infections. Published by Elsevier B.V.

  7. Antioxidant activities of chestnut nut of Castanea sativa Mill. (cultivar 'Judia') as function of origin ecosystem.

    Science.gov (United States)

    Dinis, Lia-Tânia; Oliveira, Maria Manuela; Almeida, José; Costa, Rita; Gomes-Laranjo, José; Peixoto, Francisco

    2012-05-01

    The antioxidant properties of different ecotypes of chestnut nut (cv. Judia) were studied. Total phenolics and flavonoids were also determinated. Total phenolics amount ranged from 9.6mg/g of GAE (hottest ecotype, Murça) to 19.4mg/g of GAE (coldest ecotype, Valpaços). Gallic and ellagic acid were the predominant compounds and Valpaços had the highest values while, Murça had the lowest ones. The antioxidant capacity of ethanolic extracts were evaluated through several biochemical essays: ABTS (2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid)) and DPPH (2,2-diphenyl-1-picrylhydrazyl) radical-scavenging activity, FRAP (ferric reducing/antioxidant power) and inhibition of oxidative haemolysis in erythrocytes. In order to evaluate the antioxidant efficiency of each ecotype, the EC50 values were calculated. Once again Valpaços revealed the best antioxidant properties, presenting much lower EC50 values. Climatic conditions influence seems to be a limiting factor for production of phenolic compounds and consequently for the antioxidant properties of chestnut nuts. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Antitrichomonal and antioxidant activities of Dorstenia barteri and Dorstenia convexa

    Directory of Open Access Journals (Sweden)

    N.O.A. Omisore

    2005-07-01

    Full Text Available Dorstenia barteri and D. convexa extracts and some isolated components of the former were investigated for effectiveness against Trichomonas gallinarum and compared with quercetin and quercitrin. The antioxidant activity of the extracts/compounds was also determined. The minimum lethal concentrations (MLCs for the extract of D. barteri leaves and twigs at 24 h were found to be 15.625 and 15.625 µg/ml, respectively. However, the MLCs of the leaf and twig extract of D. convexa were 125 and 437.5 µg/ml, respectively. The prenylated and geranylated chalcones were as active as the prenylated flavones, 6-prenylapigenin and the diprenylated derivative 6,8-diprenyleridictyol. The order of the antitrichomonal activity of the compounds at 24 h was: quercetin (0.121 µg/ml > quercitrin (0.244 µg/ml > or = bartericin B (0.244 µg/ml > bartericin A (0.73 µg/ml > stigmasterol (0.98 µg/ml > 6,8-diprenyleridictyol = isobavachalcone = dorsmanin F (31.25 µg/ml. D. barteri extracts, quercitrin, and bartericin A, and the prenylated flavonoids had potent antioxidant properties. The twig extract of D. barteri was more potent than the leaf extract. Moderate (EC50 >50 µg/ml and high (EC50 <50 µg/ml antioxidant activities were detected in the leaf and twig extracts of D. barteri and the prenylated flavonoids. Prenylated flavonoids and the isolated compounds with antioxidant properties described here may account for the anti-inflammatory action of these extracts. The antitrichomonal and antioxidant activities shown by the extracts and compounds in this study are consistent with the ethnomedicinal and local use of the Dorstenia species studied.

  9. Antiviral Activity and Resistance Analysis of NS3/4A Protease Inhibitor Grazoprevir and NS5A Inhibitor Elbasvir in Hepatitis C Virus GT4 Replicons.

    Science.gov (United States)

    Asante-Appiah, Ernest; Curry, Stephanie; McMonagle, Patricia; Ingravallo, Paul; Chase, Robert; Nickle, David; Qiu, Ping; Howe, Anita; Lahser, Frederick C

    2017-07-01

    Although genotype 4 (GT4)-infected patients represent a minor overall percentage of the global hepatitis C virus (HCV)-infected population, the high prevalence of the genotype in specific geographic regions coupled with substantial sequence diversity makes it an important genotype to study for antiviral drug discovery and development. We evaluated two direct-acting antiviral agents-grazoprevir, an HCV NS3/4A protease inhibitor, and elbasvir, an HCV NS5A inhibitor-in GT4 replicons prior to clinical studies in this genotype. Following a bioinformatics analysis of available GT4 sequences, a set of replicons bearing representative GT4 clinical isolates was generated. For grazoprevir, the 50% effective concentration (EC 50 ) against the replicon bearing the reference GT4a (ED43) NS3 protease and NS4A was 0.7 nM. The median EC 50 for grazoprevir against chimeric replicons encoding NS3/4A sequences from GT4 clinical isolates was 0.2 nM (range, 0.11 to 0.33 nM; n = 5). The difficulty in establishing replicons bearing NS3/4A resistance-associated substitutions was substantially overcome with the identification of a G162R adaptive substitution in NS3. Single NS3 substitutions D168A/V identified from de novo resistance selection studies reduced grazoprevir antiviral activity by 137- and 47-fold, respectively, in the background of the G162R replicon. For elbasvir, the EC 50 against the replicon bearing the reference full-length GT4a (ED43) NS5A gene was 0.0002 nM. The median EC 50 for elbasvir against chimeric replicons bearing clinical isolates from GT4 was 0.0007 nM (range, 0.0002 to 34 nM; n = 14). De novo resistance selection studies in GT4 demonstrated a high propensity to suppress the emergence of amino acid substitutions that confer high-potency reductions to elbasvir. Phenotypic characterization of the NS5A amino acid substitutions identified (L30F, L30S, M31V, and Y93H) indicated that they conferred 15-, 4-, 2.5-, and 7.5-fold potency losses, respectively, to elbasvir

  10. Natural resistance to ascorbic acid induced oxidative stress is mainly mediated by catalase activity in human cancer cells and catalase-silencing sensitizes to oxidative stress

    Directory of Open Access Journals (Sweden)

    Klingelhoeffer Christoph

    2012-05-01

    Full Text Available Abstract Background Ascorbic acid demonstrates a cytotoxic effect by generating hydrogen peroxide, a reactive oxygen species (ROS involved in oxidative cell stress. A panel of eleven human cancer cell lines, glioblastoma and carcinoma, were exposed to serial dilutions of ascorbic acid (5-100 mmol/L. The purpose of this study was to analyse the impact of catalase, an important hydrogen peroxide-detoxifying enzyme, on the resistance of cancer cells to ascorbic acid mediated oxidative stress. Methods Effective concentration (EC50 values, which indicate the concentration of ascorbic acid that reduced the number of viable cells by 50%, were detected with the crystal violet assay. The level of intracellular catalase protein and enzyme activity was determined. Expression of catalase was silenced by catalase-specific short hairpin RNA (sh-RNA in BT-20 breast carcinoma cells. Oxidative cell stress induced apoptosis was measured by a caspase luminescent assay. Results The tested human cancer cell lines demonstrated obvious differences in their resistance to ascorbic acid mediated oxidative cell stress. Forty-five percent of the cell lines had an EC50 > 20 mmol/L and fifty-five percent had an EC50 50 of 2.6–5.5 mmol/L, glioblastoma cells were the most susceptible cancer cell lines analysed in this study. A correlation between catalase activity and the susceptibility to ascorbic acid was observed. To study the possible protective role of catalase on the resistance of cancer cells to oxidative cell stress, the expression of catalase in the breast carcinoma cell line BT-20, which cells were highly resistant to the exposure to ascorbic acid (EC50: 94,9 mmol/L, was silenced with specific sh-RNA. The effect was that catalase-silenced BT-20 cells (BT-20 KD-CAT became more susceptible to high concentrations of ascorbic acid (50 and 100 mmol/L. Conclusions Fifty-five percent of the human cancer cell lines tested were unable to protect themselves

  11. Chemical composition and evaluation of antibacterial and antioxidant activities of the essential oil of Croton urucurana Baillon (Euphorbiaceae) stem bark

    International Nuclear Information System (INIS)

    Simionatto, Euclesio; Bonani, Vanderlea F.L.; Peruzzo, Gisele M.; Peres, Marize T.L.P.; Hess, Sania C.; Morel, Ademir Farias Morel; Stuker, Caroline Z.; Poppi, Nilva Re; Raposo Junior, Jorge Luiz

    2007-01-01

    The essential oil obtained from the stem bark of Croton urucurana Baillon (Euphorbiaceae) was analysed by GC and GC-MS. 83 compounds were identified and borneol (14.7%), bornyl acetate (5.2%), 1-isopropyl-7-methyl-4-methylene-1,3,4,5,6,8-hexahydro-2H-naphthalane-4a-ol (14.7%), sesquicineole (10.5%) and γ-gurjunene epoxide (5.4%) were the main components. The EC 50 value of the crude essential oil in the DPPH free radical scavenging assay was 3.21 mg mL -1 . The fraction of the crude essential oil that presented antioxidant activity was purified by prep-TLC on silica gel. GC and GC-MS analysis revealed that a-bisabolol (38.3%), a-eudesmol (9.3%) and guaiol (8.2%) were the main components of the antioxidant fraction. The EC 50 value measured for the bioactive oil fraction in the DPPH assay was 1.05 mg mL -1 . The antimicrobial activity of the crude essential oil was assayed against seven Gram-positive and Gram-negative bacteria and three yeasts. Measured MIC values ranged from 1.25 to 10.00 mg mL -1 . (author)

  12. Composition, antioxidant and antimicrobial activity of the essential oils of a full grown tree of Pinus cembra L. from the Calimani mountains (Romania

    Directory of Open Access Journals (Sweden)

    Apetrei Lungu Cristina

    2013-01-01

    Full Text Available This study was carried out to investigate the chemical composition, the antioxidant and antimicrobial effects of the essential oils of Pinus cembra L. needles and twigs. The chemical composition was analyzed using both GC and GC-MS techniques. α-Pinene (69.14% was the major constituent of the needle essential oil while the twig essential oil was characterized by a high content of limonene+ β-phellandrene (40.97% and α-pinene (24.94%. The needle and twig essential oils showed weak DPPH radical scavenging effects (EC50=19.93±0.75 and EC50=18.66±0.70 mg ml-1, respectively. In antimicrobial assays, both essential oils showed high activity against Sarcina lutea and Staphylococcus aureus and no activity against Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. The needle and twig essential oils had similar antimicrobial effects against Sarcina lutea with MIC and MBC values of 0.12 and 0.24 mg ml-1, respectively. The twig essential oil (MIC=1.95 mg ml-1, MBC=3.9 mg ml-1 was more active against Staphylococcus aureus than the needle essential oil (MIC=3.9 mg ml-1, MBC=15.62 mg ml-1 and also exhibited a moderate activity against Candida albicans (MIC=7.81 mg ml-1, MFC=15.62 mg ml-1.

  13. In vitro anthelmintic and cytotoxicity activities the Digitaria insularis (Poaceae).

    Science.gov (United States)

    Santos, Francianne Oliveira; de Lima, Hélimar Gonçalves; de Souza Santos, Nathália Silva; Serra, Taiane Menezes; Uzeda, Rosângela Soares; Reis, Isabella Mary Alves; Botura, Mariana Borges; Branco, Alexsandro; Batatinha, Maria José Moreira

    2017-10-15

    This study aimed to evaluate the in vitro activity of D. insularis extracts and fractions against gastrointestinal nematodes of goats and its cytotoxicity on Vero cells. The egg hatch (EHT) and larval motility (LMT) tests were conducted to investigate the anthelmintic effects of the crude hydroethanolic (CH), ethyl acetate (EA), butanolic (BT) and residual hydroethanolic (RH) extracts. The elution of the active extract (EA) on column chromatography (SiO 2 ) using organic solvents furnished six fractions (FR1 to FR6), which were also tested. Cytotoxicity was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Trypan Blue exclusion assays. All extracts, FR2 and FR3, inhibited egg hatching in a concentration-dependent manner. The EHT led to EC 50 values (effective concentration 50%) of 0.64; 0.69; 0.77; 0.96; 0.27 and 0.65mg/mL for CH, EA, BT, RH, FR2 and FR3, respectively. However, the extracts exhibited low effect on the motility of L 3. In the cytotoxicity evaluation (MTT assay), the IC 50 (inhibitory concentration 50%) was 1.18 (EA), 1.65 (FR2) and 1.59mg/mL (FR3), which was relatively high (low toxicity) in comparison to the EC 50 values in EHT, mainly for FR2. The chemical analyses of most active fractions (FR2) by Liquid Chromatography coupled to Mass Spectrometry (LC-MS) led the characterization of the flavones tricin and diosmetin. These results showed the high anthelmintic effect and low cytotoxicity of D. insularis and also that the flavones can be probably responsible for the nematocidal activity of this plant. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. NOpiates: Novel Dual Action Neuronal Nitric Oxide Synthase Inhibitors with μ-Opioid Agonist Activity.

    Science.gov (United States)

    Renton, Paul; Green, Brenda; Maddaford, Shawn; Rakhit, Suman; Andrews, John S

    2012-03-08

    A novel series of benzimidazole designed multiple ligands (DMLs) with activity at the neuronal nitric oxide synthase (nNOS) enzyme and the μ-opioid receptor was developed. Targeting of the structurally dissimilar heme-containing enzyme and the μ-opioid GPCR was predicated on the modulatory role of nitric oxide on μ-opioid receptor function. Structure-activity relationship studies yielded lead compound 24 with excellent nNOS inhibitory activity (IC50 = 0.44 μM), selectivity over both endothelial nitric oxide synthase (10-fold) and inducible nitric oxide synthase (125-fold), and potent μ-opioid binding affinity, K i = 5.4 nM. The functional activity as measured in the cyclic adenosine monosphospate secondary messenger assay resulted in full agonist activity (EC50 = 0.34 μM). This work represents a novel approach in the development of new analgesics for the treatment of pain.

  15. Anti-inflammatory and angiogenic activity of polysaccharide extract obtained from Tibetan kefir.

    Science.gov (United States)

    Prado, Maria Rosa Machado; Boller, Christian; Zibetti, Rosiane Guetter Mello; de Souza, Daiany; Pedroso, Luciana Lopes; Soccol, Carlos Ricardo

    2016-11-01

    The search for new bioactive molecules is a driving force for research pharmaceutical industries, especially those molecules obtained from fermentation. The molecules possessing angiogenic and anti-inflammatory attributes have attracted attention and are the focus of this study. Angiogenic activity from kefir polysaccharide extract, via chorioallantoic membrane assay, exhibited a pro-angiogenic effect compared with vascular endothelial factor (pro-angiogenic) and hydrocortisone (anti-angiogenic) activity as standards with an EC50 of 192ng/mL. In terms of anti-inflammatory activity determined via hyaluronidase enzyme assay, kefir polysaccharide extract inhibited the enzyme with a minimal activity of 2.08mg/mL and a maximum activity of 2.57mg/mL. For pharmaceutical purposes, kefir polysaccharide extract is considered to be safe because it does not inhibit VERO cells in cytotoxicity assays. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Anti-Trypanosoma cruzi and cytotoxic activities of Eugenia uniflora L.

    Science.gov (United States)

    Santos, Karla K A; Matias, Edinardo F F; Tintino, Saulo R; Souza, Celestina E S; Braga, Maria F B M; Guedes, Gláucia M M; Rolón, Miriam; Vega, Celeste; de Arias, Antonieta Rojas; Costa, José G M; Menezes, Irwin R A; Coutinho, Henrique D M

    2012-05-01

    Chagas disease is caused by Trypanosoma cruzi, being considered a public health problem. An alternative to combat this pathogen is the use of natural products isolated from fruits such as Eugenia uniflora, a plant used by traditional communities as food and medicine due to its antimicrobial and biological activities. Ethanolic extract from E. uniflora was used to evaluate in vitro anti-epimastigote and cytotoxic activity. This is the first record of anti-Trypanosoma activity of E. uniflora, demonstrating that a concentration presenting 50% of activity (EC(50)) was 62.76 μg/mL. Minimum inhibitory concentration (MIC) was ≤ 1024 μg/mL. Our results indicate that E. uniflora could be a source of plant-derived natural products with anti-epimastigote activity with low toxicity. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Quantitative structure–activity relationships for chronic toxicity of alkyl-chrysenes and alkyl-benz[a]anthracenes to Japanese medaka embryos (Oryzias latipes)

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Hongkang [Department of Biology, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Morandi, Garrett D. [School of Environmental Studies, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Brown, R. Stephen [School of Environmental Studies, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Department of Chemistry, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Snieckus, Victor; Rantanen, Toni [Department of Chemistry, Queen' s University, Kingston, Ontario K7L3N6 (Canada); Jørgensen, Kåre B. [Department of Mathematics and Natural Sciences, University of Stavanger, 4036 Stavanger (Norway); Hodson, Peter V., E-mail: peter.hodson@queensu.ca [Department of Biology, Queen' s University, Kingston, Ontario K7L3N6 (Canada); School of Environmental Studies, Queen' s University, Kingston, Ontario K7L3N6 (Canada)

    2015-02-15

    Highlights: • Medaka embryos were exposed to alkyl chrysenes and benzo[a]anthracenes (BAA). • Concentrations were kept constant by partition controlled delivery. • Chrysene was not toxic within solubility limits, in contrast to BAA. • Alkylation increased the toxicity of chrysene and BAA. • Toxicity was related to hydrophobicity and to specific modes of action. - Abstract: Alkylated polycyclic aromatic hydrocarbons (alkyl-PAHs) are a class of compounds found at significant concentrations in crude oils, and likely the main constituents responsible for the chronic toxicity of oil to fish. Alkyl substituents at different locations on the aromatic rings change the size and shape of PAH molecules, which results in different interactions with tissue receptors and different severities of toxicity. The present study is the first to report the toxicity of several alkylated derivatives of chrysene and benz[a]anthracene to the embryos of Japanese medaka (Oryzias latipes) using the partition controlled delivery (PCD) method of exposure. The PCD method maintained the desired exposure concentrations by equilibrium partitioning of hydrophobic test compounds from polydimethylsiloxane (PDMS) films. Test concentrations declined by only 13% over a period of 17 days. Based on the prevalence of signs of blue sac disease (BSD), as expressed by median effective concentrations (EC50s), benz[a]anthracene (B[a]A) was more toxic than chrysene. Alkylation generally increased toxicity, except at position 2 of B[a]A. Alkyl-PAHs substituted in the middle region had a lower EC50 than those substituted at the distal region. Except for B[a]A and 7-methylbenz[a]anthracene (7-MB), estimated EC50 values were higher than their solubility limits, which resulted in limited toxicity within the range of test concentrations. The regression between log EC50s and log K{sub ow} values provided a rough estimation of structure–activity relationships for alkyl-PAHs, but K{sub ow} alone did not provide

  18. [Development of a Computer-aided Diagnosis System to Distinguish between Benign and Malignant Mammary Tumors in Dynamic Magnetic Resonance Images: Automatic Detection of the Position with the Strongest Washout Effect in the Tumor].

    Science.gov (United States)

    Miyazaki, Yoshiaki; Tabata, Nobuyuki; Taroura, Tomomi; Shinozaki, Kenji; Kubo, Yuichiro; Tokunaga, Eriko; Taguchi, Kenichi

    We propose a computer-aided diagnostic (CAD) system that uses time-intensity curves to distinguish between benign and malignant mammary tumors. Many malignant tumors show a washout pattern in time-intensity curves. Therefore, we designed a program that automatically detects the position with the strongest washout effect using the technique, such as the subtraction technique, which extracts only the washout area in the tumor, and by scanning data in 2×2 pixel region of interest (ROI). Operation of this independently developed program was verified using a phantom system that simulated tumors. In three cases of malignant tumors, the washout pattern detection rate in images with manually set ROI was ≤6%, whereas the detection rate with our novel method was 100%. In one case of a benign tumor, when the same method was used, we checked that there was no washout effect and detected the persistent pattern. Thus, the distinction between benign and malignant tumors using our method was completely consistent with the pathological diagnoses made. Our novel method is therefore effective for differentiating between benign and malignant mammary tumors in dynamic magnetic resonance images.

  19. Structure-based design, synthesis, and biological evaluation of novel pyrrolyl aryl sulfones: HIV-1 non-nucleoside reverse transcriptase inhibitors active at nanomolar concentrations.

    Science.gov (United States)

    Artico, M; Silvestri, R; Pagnozzi, E; Bruno, B; Novellino, E; Greco, G; Massa, S; Ettorre, A; Loi, A G; Scintu, F; La Colla, P

    2000-05-04

    Pyrrolyl aryl sulfones (PASs) have been recently reported as a new class of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitors acting at the non-nucleoside binding site of this enzyme (Artico, M.; et al. J. Med. Chem. 1996, 39, 522-530). Compound 3, the most potent inhibitor within the series (EC(50) = 0.14 microM, IC(50) = 0.4 microM, and SI > 1429), was then selected as a lead compound for a synthetic project based on molecular modeling studies. Using the three-dimensional structure of RT cocrystallized with the alpha-APA derivative R95845, we derived a model of the RT/3 complex by taking into account previously developed structure-activity relationships. Inspection of this model and docking calculations on virtual compounds prompted the design of novel PAS derivatives and related analogues. Our computational approach proved to be effective in making qualitative predictions, that is in discriminating active versus inactive compounds. Among the compounds synthesized and tested, 20 was the most active one, with EC(50) = 0.045 microM, IC(50) = 0.05 microM, and SI = 5333. Compared with the lead 3, these values represent a 3- and 8-fold improvement in the cell-based and enzyme assays, respectively, together with the highest selectivity achieved so far in the PAS series.

  20. A cyclic GMP-dependent calcium-activated chloride current in smooth-muscle cells from rat mesenteric resistance arteries

    DEFF Research Database (Denmark)

    Matchkov, Vladimir; Aalkjær, Christian; Nilsson, Holger

    2004-01-01

    We have previously demonstrated the presence of a cyclic GMP (cGMP)-dependent calcium-activated inward current in vascular smooth-muscle cells, and suggested this to be of importance in synchronizing smooth-muscle contraction. Here we demonstrate the characteristics of this current. Using......M) in the pipette solution. The current was found to be a calcium-activated chloride current with an absolute requirement for cyclic GMP (EC50 6.4 microM). The current could be activated by the constitutively active subunit of PKG. Current activation was blocked by the protein kinase G antagonist Rp-8-Br-PET-cGMP...... differed from those of the calcium-activated chloride current in pulmonary myocytes, which was cGMP-independent, exhibited a high sensitivity to inhibition by niflumic acid, was unaffected by zinc ions, and showed outward current rectification as has previously been reported for this current. Under...

  1. Synthesis and proapoptotic activity of oleanolic acid derived amides.

    Science.gov (United States)

    Heller, Lucie; Knorrscheidt, Anja; Flemming, Franziska; Wiemann, Jana; Sommerwerk, Sven; Pavel, Ioana Z; Al-Harrasi, Ahmed; Csuk, René

    2016-10-01

    Thirty-one different 3-O-acetyl-OA derived amides have been prepared and screened for their cytotoxic activity. In the SRB assays nearly all the carboxamides displayed good cytotoxicity in the low μM range for several human tumor cell lines. Low EC50 values were obtained especially for the picolinylamides 14-16, for a N-[2-(dimethylamino)-ethyl] derivative 27 and a N-[2-(pyrrolinyl)-ethyl] carboxamide 28. These compounds were submitted to an extensive biological testing and proved compound 15 to act mainly by an arrest of the tumor cells in the S phase of the cell cycle. Cell death occurred by autophagy while compounds 27 and 28 triggered apoptosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Anti-cytomegalovirus activity of the anthraquinone atanyl blue PRL.

    Science.gov (United States)

    Alam, Zohaib; Al-Mahdi, Zainab; Zhu, Yali; McKee, Zachary; Parris, Deborah S; Parikh, Hardik I; Kellogg, Glen E; Kuchta, Alison; McVoy, Michael A

    2015-02-01

    Human cytomegalovirus (CMV) causes significant disease in immunocompromised patients and serious birth defects if acquired in utero. Available CMV antivirals target the viral DNA polymerase, have significant toxicities, and suffer from resistance. New drugs targeting different pathways would be beneficial. The anthraquinone emodin is proposed to inhibit herpes simplex virus by blocking the viral nuclease. Emodin and related anthraquinones are also reported to inhibit CMV. In the present study, emodin reduced CMV infectious yield with an EC50 of 4.9μM but was cytotoxic at concentrations only twofold higher. Related anthraquinones acid blue 40 and alizarin violet R inhibited CMV at only high concentrations (238-265μM) that were also cytotoxic. However, atanyl blue PRL inhibited infectious yield of CMV with an EC50 of 6.3μM, significantly below its 50% cytotoxic concentration of 216μM. Atanyl blue PRL reduced CMV infectivity and inhibited spread. When added up to 1h after infection, it dramatically reduced CMV immediate early protein expression and blocked viral DNA synthesis. However, it had no antiviral activity when added 24h after infection. Interestingly, atanyl blue PRL inhibited nuclease activities of purified CMV UL98 protein with IC50 of 4.5 and 9.3μM. These results indicate that atanyl blue PRL targets very early post-entry events in CMV replication and suggest it may act through inhibition of UL98, making it a novel CMV inhibitor. This compound may provide valuable insights into molecular events that occur at the earliest times post-infection and serve as a lead structure for antiviral development. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Activation of neural cholecystokinin-1 receptors induces relaxation of the isolated rat duodenum which is reduced by nitric oxide synthase inhibitors

    Directory of Open Access Journals (Sweden)

    S.R. Martins

    2006-02-01

    Full Text Available Cholecystokinin (CCK influences gastrointestinal motility, by acting on central and peripheral receptors. The aim of the present study was to determine whether CCK has any effect on isolated duodenum longitudinal muscle activity and to characterize the mechanisms involved. Isolated segments of the rat proximal duodenum were mounted for the recording of isometric contractions of longitudinal muscle in the presence of atropine and guanethidine. CCK-8S (EC50: 39; 95% CI: 4.1-152 nM and cerulein (EC50: 58; 95% CI: 18-281 nM induced a concentration-dependent and tetrodotoxin-sensitive relaxation. Nomeganitro-L-arginine (L-NOARG reduced CCK-8S- and cerulein-induced relaxation (IC50: 5.2; 95% CI: 2.5-18 µM in a concentration-dependent manner. The magnitude of 300 nM CCK-8S-induced relaxation was reduced by 100 µM L-NOARG from 73 ± 5.1 to 19 ± 3.5% in an L-arginine but not D-arginine preventable manner. The CCK-1 receptor antagonists proglumide, lorglumide and devazepide, but not the CCK-2 receptor antagonist L-365,260, antagonized CCK-8S-induced relaxation in a concentration-dependent manner. These findings suggest that CCK-8S and cerulein activate intrinsic nitrergic nerves acting on CCK-1 receptors in order to cause relaxation of the rat duodenum longitudinal muscle.

  4. Anticholinergic, antihistaminic, and antiserotonergic activity of n-hexane extract of Zanthoxylum alatum seeds on isolated tissue preparations: An ex vivo study.

    Science.gov (United States)

    Saikia, Beenita; Barua, Chandana Choudhury; Haloi, Prakash; Patowary, Pompy

    2017-01-01

    The aim of this study was to evaluate anticholinergic, antihistaminic, and antiserotonergic activity of the n-hexane extract of the seeds of Zanthoxylum alatum (ZAHE) on isolated ileum of rat and guinea pig and fundus of rat. ZAHE was prepared using soxhlet extraction and cumulative concentration response curves were constructed using various doses on the tissues for acetylcholine (ACh), 5-hydroxytryptamine (5-HT), and histamine with or without n-hexane extract. Atropine, ketanserin, and pheniramine maleate were used as antagonists for ACh, serotonin, and histamine, respectively. ZAHE-induced concentration-dependent inhibition of isolated ileum and fundus in rat and ileum of guinea pig. The half maximal effective concentration (EC 50 ) of ACh in the presence of atropine (10 -6 M; P pheniramine maleate (10 -6 M; P < 0.01) and ZAHE (300 μg/ml; P < 0.01 and 1000 μg/ml; P < 0.05) was also significantly higher than EC 50 of histamine alone. From the study, it was observed that ZAHE shows significant anticholinergic, antiserotonergic, and antihistaminic activity. The study provides sufficient evidence that the seeds can be used in gastric disorders, cough, chest infection, etc., as per folklore claims.

  5. N-(4-((E)-3-arylacryloyl)phenyl)acetamide derivatives and their antileishmanial activity

    International Nuclear Information System (INIS)

    Pacheco, Dency J.; Trilleras, Jorge; Prent, Luis; Coaves, Tobinson; Quiroga, Jairo; Gutierrez, Jennifer; Delgado, Gabriela; Marin, Juan C.

    2013-01-01

    The antileishmanial activity of a series of enonic derivatives (chalcones) synthesized via Claisen-Schmidt condensation reactions assisted by ultrasonic radiation was characterized by analyzing their cytotoxicity against Leishmania (Viannia) panamensis promastigotes, a species responsible for over 90% of Leishmania cases in Colombia. Two compounds were active against Leishmania with selectivity indexes of LC 50 EC 50 -1 (lethal concentration 50 and effective concentration 50) higher than 27 and 3, respectively. These results suggest that a substitution on one of the two chalcone rings (aromatic ring A) with oxygen is convenient. Compound 3g should be further investigated for its antileishmanial activity, especially for being easy to obtain in high yields, making it possible to produce drugs for the treatment of cutaneous leishmaniasis. (author)

  6. Heterocyclic Schiff bases as non toxic antioxidants: Solvent effect, structure activity relationship and mechanism of action

    Science.gov (United States)

    Shanty, Angamaly Antony; Mohanan, Puzhavoorparambil Velayudhan

    2018-03-01

    Phenolic heterocyclic imine based Schiff bases from Thiophene-2-carboxaldehyde and Pyrrole-2-carboxaldehyde were synthesized and characterized as novel antioxidants. The solvent effects of these Schiff bases were determined and compared with standard antioxidants, BHA employing DPPH assay and ABTS assay. Fixed reaction time and Steady state measurement were used for study. IC50 and EC50 were calculated. Structure-activity relationship revealed that the electron donating group in the phenolic ring increases the activity where as the electron withdrawing moiety decreases the activity. The Schiff base derivatives showed antioxidant property by two different pathways namely SPLET and HAT mechanisms in DPPH assay. While in ABTS method, the reaction between ABTS radical and Schiff bases involves electron transfer followed by proton transfer (ET-PT) mechanism. The cytotoxicity of these compounds has been evaluated by MTT assay. The results showed that all these compounds are non toxic in nature.

  7. Activity and Safety of Synthetic Lectins Based on Benzoboroxole-Functionalized Polymers for Inhibition of HIV Entry

    Science.gov (United States)

    Mahalingam, Alamelu; Geonnotti, Anthony R.; Balzarini, Jan; Kiser, Patrick F.

    2011-01-01

    Lectins derived from plant and microbial sources constitute a vital class of entry inhibitors that target the oligomannose residues on the HIV envelope gp120. Despite their potency and specificity, success of lectin-based entry inhibitors may be impeded by issues in regards to economical production, formulation and potential mitogenicity. Therefore, there exists a gap in the HIV therapeutics pipeline that underscores the need for mass producible, synthetic, broad-spectrum, and biocomptabile inhibitors of HIV entry. Here, we present the development of a polymeric synthetic lectin, based on benzoboroxole (BzB), which exhibits weak affinity (~25 M−1) for non-reducing sugars, similar to those found on the HIV envelope. High molecular weight BzB-functionalized polymers demonstrated antiviral activity that increased with an increase in ligand density and molecular weight of the polymer construct; revealing that polyvalency improves activity. Polymers showed significant increase in activity from 25 to 75 mol% BzB functionalization with EC50 of 15 μM and 15 nM, respectively. A further increase in mole functionalization to 90% resulted in an increase of the EC50 (59 ± 5 nM), likely due to the elongated rigid structure of the polymer chain compelled by electrostatic repulsion between the boronic acid groups. An increase in molecular weight of the polymer at 50 mol% BzB functionalization showed a gradual but significant increase in antiviral activity, with the highest activity seen with the 382 kDa polymer (EC50 of 1.1 ± 0.5 nM in CEM cells and 11 ± 3 nM in TZM-bl cells). Supplementing the polymer backbone with 10 mol% sulfonic acid not only increased the aqueous solubility of the polymers by at least 50-fold, but also demonstrated a synergistic increase in anti-HIV activity (4.0 ± 1.5 nM in TZM-bl cells), possibly due to electrostatic interactions between the negatively charged polymer backbone and the positively charged V3-loop in the gp120. The benzoboroxole

  8. Linking algal growth inhibition to chemical activity

    DEFF Research Database (Denmark)

    Schmidt, Stine N.; Mayer, Philipp

    Unitless chemical activity, expressing the energetic level of a compound relative to its energetic level in pure liquid [0-1], has proven useful to quantify the effective exposure to hydrophobic organic compounds through both aerial and aqueous media. Several studies have linked toxicity to chemi......Unitless chemical activity, expressing the energetic level of a compound relative to its energetic level in pure liquid [0-1], has proven useful to quantify the effective exposure to hydrophobic organic compounds through both aerial and aqueous media. Several studies have linked toxicity...... to chemical activity, as opposed to e.g. the total concentration. Baseline toxicity (narcosis) for neutral hydrophobic organic compounds has been shown to initiate in the narrow chemical activity range of 0.01 to 0.1. This presentation focuses on linking algal growth inhibition to chemical activity......-polar liquids were applied to challenge the chemical activity range for baseline toxicity. For each compound, the effective activity (Ea50) was estimated as the ratio of the effective concentration (EC50) and water solubility. Of these ratios, 90% were within the expected chemical activity range of 0.01 to 0...

  9. The binding of activated Gαq to phospholipase C-β exhibits anomalous affinity.

    Science.gov (United States)

    Navaratnarajah, Punya; Gershenson, Anne; Ross, Elliott M

    2017-10-06

    Upon activation by the G q family of Gα subunits, Gβγ subunits, and some Rho family GTPases, phospholipase C-β (PLC-β) isoforms hydrolyze phosphatidylinositol 4,5-bisphosphate to the second messengers inositol 1,4,5-trisphosphate and diacylglycerol. PLC-β isoforms also function as GTPase-activating proteins, potentiating G q deactivation. To elucidate the mechanism of this mutual regulation, we measured the thermodynamics and kinetics of PLC-β3 binding to Gα q FRET and fluorescence correlation spectroscopy, two physically distinct methods, both yielded K d values of about 200 nm for PLC-β3-Gα q binding. This K d is 50-100 times greater than the EC 50 for Gα q -mediated PLC-β3 activation and for the Gα q GTPase-activating protein activity of PLC-β. The measured K d was not altered either by the presence of phospholipid vesicles, phosphatidylinositol 4,5-bisphosphate and Ca 2+ , or by the identity of the fluorescent labels. FRET-based kinetic measurements were also consistent with a K d of 200 nm We determined that PLC-β3 hysteresis, whereby PLC-β3 remains active for some time following either Gα q -PLC-β3 dissociation or PLC-β3-potentiated Gα q deactivation, is not sufficient to explain the observed discrepancy between EC 50 and K d These results indicate that the mechanism by which Gα q and PLC-β3 mutually regulate each other is far more complex than a simple, two-state allosteric model and instead is probably kinetically determined. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. A protein chip membrane-capture assay for botulinum neurotoxin activity

    International Nuclear Information System (INIS)

    Marconi, Severine; Ferracci, Geraldine; Berthomieu, Maelys; Kozaki, Shunji; Miquelis, Raymond; Boucraut, Jose; Seagar, Michael

    2008-01-01

    Botulinum neurotoxins A and B (BoNT/A and B) are neuromuscular blocking agents which inhibit neurotransmission by cleaving the intra-cellular presynaptic SNARE proteins SNAP-25 and VAMP2, localized respectively in plasma membrane and synaptic vesicles. These neurotoxins are both dangerous pathogens and powerful therapeutic agents with numerous clinical and cosmetic applications. Consequently there is a need for in vitro assays of their biological activity to screen for potential inhibitors and to replace the widely used in vivo mouse assay. Surface plasmon resonance (SPR) was used to measure membrane vesicle capture by antibodies against SNAP-25 and VAMP2. Substrate cleavage by BoNTs modified capture providing a method to assay toxin activity. Firstly using synaptic vesicles as a substrate, a comparison of the EC 50 s for BoNT/B obtained by SPR, ELISA or flow cytometry indicated similar sensitivity although SPR assays were more rapid. Sonication of brain or neuronal cultures generated plasma membrane fragments with accessible intra-cellular epitopes adapted to measurement of BoNT/A activity. SPR responses were proportional to antigen concentration permitting detection of as little as 4 pM SNAP-25 in crude lysates. BoNT/A activity was assayed using monoclonal antibodies that specifically recognize a SNAP-25 epitope generated by the proteolytic action of the toxin. Incubation of intact primary cultured neurons with BoNT/A yielded an EC 50 of 0.5 pM. The SPR biosensor method was sensitive enough to monitor BoNT/A and B activity in cells cultured in a 96-well format providing an alternative to experimental animals for toxicological assays

  11. Synthesis and antifungal activity of the derivatives of novel pyrazole carboxamide and isoxazolol pyrazole carboxylate.

    Science.gov (United States)

    Sun, Jialong; Zhou, Yuanming

    2015-03-09

    A series of pyrazole carboxamide and isoxazolol pyrazole carboxylate derivatives were designed and synthesized in this study. The structures of the compounds were elucidated based on spectral data (infrared, proton nuclear magnetic resonance and mass spectroscopy). Then, all of the compounds were bioassayed in vitro against four types of phytopathogenic fungi (Alternaria porri, Marssonina coronaria, Cercospora petroselini and Rhizoctonia solani) using the mycelium growth inhibition method. The results showed that some of the synthesized pyrazole carboxamides displayed notable antifungal activity. The isoxazole pyrazole carboxylate 7ai exhibited significant antifungal activity against R. solani, with an EC50 value of 0.37 μg/mL. Nonetheless, this value was lower than that of the commercial fungicide, carbendazol.

  12. Synthesis and Antifungal Activity of the Derivatives of Novel Pyrazole Carboxamide and Isoxazolol Pyrazole Carboxylate

    Directory of Open Access Journals (Sweden)

    Jialong Sun

    2015-03-01

    Full Text Available A series of pyrazole carboxamide and isoxazolol pyrazole carboxylate derivatives were designed and synthesized in this study. The structures of the compounds were elucidated based on spectral data (infrared, proton nuclear magnetic resonance and mass spectroscopy. Then, all of the compounds were bioassayed in vitro against four types of phytopathogenic fungi (Alternaria porri, Marssonina coronaria, Cercospora petroselini and Rhizoctonia solani using the mycelium growth inhibition method. The results showed that some of the synthesized pyrazole carboxamides displayed notable antifungal activity. The isoxazole pyrazole carboxylate 7ai exhibited significant antifungal activity against R. solani, with an EC50 value of 0.37 μg/mL. Nonetheless, this value was lower than that of the commercial fungicide, carbendazol.

  13. Molecular Design, Synthesis and Trypanocidal Activity of Dipeptidyl Nitriles as Cruzain Inhibitors

    Science.gov (United States)

    Avelar, Leandro A. A.; Camilo, Cristian D.; de Albuquerque, Sérgio; Fernandes, William B.; Gonçalez, Cristiana; Kenny, Peter W.; Leitão, Andrei; McKerrow, James H.; Montanari, Carlos A.; Orozco, Erika V. Meñaca; Ribeiro, Jean F. R.; Rocha, Josmar R.; Rosini, Fabiana; Saidel, Marta E.

    2015-01-01

    A series of compounds based on the dipeptidyl nitrile scaffold were synthesized and assayed for their inhibitory activity against the T. cruzi cysteine protease cruzain. Structure activity relationships (SARs) were established using three, eleven and twelve variations respectively at the P1, P2 and P3 positions. A K i value of 16 nM was observed for the most potent of these inhibitors which reflects a degree of non-additivity in the SAR. An X-ray crystal structure was determined for the ligand-protein complex for the structural prototype for the series. Twenty three inhibitors were also evaluated for their anti-trypanosomal effects and an EC50 value of 28 μM was observed for the most potent of these. Although there remains scope for further optimization, the knowledge gained from this study is also transferable to the design of cruzain inhibitors based on warheads other than nitrile as well as alternative scaffolds. PMID:26173110

  14. Anti-trypanosomal activity of non-peptidic nitrile-based cysteine protease inhibitors.

    Science.gov (United States)

    Burtoloso, Antonio C B; de Albuquerque, Sérgio; Furber, Mark; Gomes, Juliana C; Gonçalez, Cristiana; Kenny, Peter W; Leitão, Andrei; Montanari, Carlos A; Quilles, José Carlos; Ribeiro, Jean F R; Rocha, Josmar R

    2017-02-01

    The cysteine protease cruzipain is considered to be a validated target for therapeutic intervention in the treatment of Chagas disease. Anti-trypanosomal activity against the CL Brener strain of T. cruzi was observed in the 0.1 μM to 1 μM range for three nitrile-based cysteine protease inhibitors based on two scaffolds known to be associated with cathepsin K inhibition. The two compounds showing the greatest potency against the trypanosome were characterized by EC50 values (0.12 μM and 0.25 μM) that were an order of magnitude lower than the corresponding Ki values measured against cruzain, a recombinant form of cruzipain, in an enzyme inhibition assay. This implies that the anti-trypanosomal activity of these two compounds may not be explained only by the inhibition of the cruzain enzyme, thereby triggering a putative polypharmacological profile towards cysteine proteases.

  15. Synthesis and Antifungal Activity of Novel Sulfone Derivatives Containing 1,3,4-Oxadiazole Moieties

    Directory of Open Access Journals (Sweden)

    Maoguo Tong

    2011-11-01

    Full Text Available A series of new sulfone compounds containing 1,3,4-oxadiazole moieties were synthesized. The structures of these compounds were confirmed by spectroscopic data (IR, 1H- and 13C-NMR and elemental analyses. Antifungal tests indicated that all the title compounds exhibited good antifungal activities against eight kinds of plant pathogenic fungi, and some showed superiority over the commercial fungicide hymexazol. Among them, compounds 5d, 5e, 5f, and 5i showed prominent activity against B. cinerea, with determined EC50 values of 5.21 μg/mL, 8.25 µg/mL, 8.03 µg/mL, and 21.00 µg/mL, respectively. The present work demonstrates that sulfone derivatives such as 5d containing a 1,3,4-oxadiazole moiety can be used as possible lead compounds for the development of potential agrochemicals.

  16. Biological activity and safety of Tripterygium extract prepared by sodium carbonate extraction.

    Science.gov (United States)

    Fang, Wei; Peng, Fan; Yi, Tao; Zhang, Cong; Wan, Chunxi; Xu, Huibi; Lam, Christopher Waikei; Yang, Xiangliang

    2012-09-17

    The commercial preparation named “Tripterygium glycosides” prepared by column chromatography has been used for the treatment of inflammatory and autoimmune diseases with significant efficacy but concurrent toxicity. The aim of this study was to reduce the toxicity of Tripterygium extracts, using cytotoxicity and anti-inflammatory activity of the three principal active components of Tripterygium wilfordii Hook. F. (TWHF)as guiding parameters. Column chromatography was replaced by sodium carbonate extraction for removing the acidic compounds and enriching epoxyditerpenoids and alkaloids in the extract. Results showed that the therapeutic index (IC50/EC50) on murine macrophage Raw 264.7 cells and rat mesangial HBZY-1 cells of the extract prepared by sodium carbonate extraction was significantly higher than that of Tripterygium glycosides(0.8 and 5.2 vs. 0.3 and 2.6, p sodium carbonate extraction may represent a potentially optimal source of medicine with good therapeutic index.

  17. Rational screening of peroxisome proliferator-activated receptor-γ agonists from natural products: potential therapeutics for heart failure.

    Science.gov (United States)

    Chen, Rui; Wan, Jing; Song, Jing; Qian, Yan; Liu, Yong; Gu, Shuiming

    2017-12-01

    Peroxisome proliferator-activated receptor-γ (PPARγ) is a member of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Activation of PPARγ pathway has been shown to enhance fatty acid oxidation, improve endothelial cell function, and decrease myocardial fibrosis in heart failure. Thus, the protein has been raised as an attractive target for heart failure therapy. This work attempted to discover new and potent PPARγ agonists from natural products using a synthetic strategy of computer virtual screening and transactivation reporter assay. A large library of structurally diverse, drug-like natural products was compiled, from which those with unsatisfactory pharmacokinetic profile and/or structurally redundant compounds were excluded. The binding mode of remaining candidates to PPARγ ligand-binding domain (LBD) was computationally modelled using molecular docking and their relative binding potency was ranked by an empirical scoring scheme. Consequently, eight commercially available hits with top scores were selected and their biological activity was determined using a cell-based reporter-gene assay. Four natural product compounds, namely ZINC13408172, ZINC4292805, ZINC44179 and ZINC901461, were identified to have high or moderate agonistic potency against human PPARγ with EC 50 values of 0.084, 2.1, 0.35 and 5.6 μM, respectively, which are comparable to or even better than that of the approved PPARγ full agonists pioglitazone (EC 50  =   0.16 μM) and rosiglitazone (EC 50  =   0.034 μM). Hydrophobic interactions and van der Waals contacts are the primary chemical forces to stabilize the complex architecture of PPARγ LBD domain with these agonist ligands, while few hydrogen bonds, salt bridges and/or π-π stacking at the complex interfaces confer selectivity and specificity for the domain-agonist recognition. The integrated in vitro-in silico screening strategy can be successfully applied to rational discovery of

  18. Chemical constituents and free radical scavenging activity of corn pollen collected from Apis mellifera hives compared to floral corn pollen at Nan, Thailand

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    Chantarudee Atip

    2012-04-01

    Full Text Available Abstract Background Bee pollen is composed of floral pollen mixed with nectar and bee secretion that is collected by foraging honey (Apis sp. and stingless bees. It is rich in nutrients, such as sugars, proteins, lipids, vitamins and flavonoids, and has been ascribed antiproliferative, anti-allergenic, anti-angiogenic and free radical scavenging activities. This research aimed at a preliminary investigation of the chemical constituents and free radical scavenging activity in A. mellifera bee pollen. Methods Bee pollen was directly collected from A. mellifera colonies in Nan province, Thailand, in June, 2010, whilst floral corn (Zea mays L. pollen was collected from the nearby corn fields. The pollen was then sequentially extracted with methanol, dichloromethane (DCM and hexane, and each crude extract was tested for free radical scavenging activity using the DPPH assay, evaluating the percentage scavenging activity and the effective concentration at 50% (EC50. The most active crude fraction from the bee pollen was then further enriched for bioactive components by silica gel 60 quick and adsorption or Sephadex LH-20 size exclusion chromatography. The purity of all fractions in each step was observed by thin layer chromatography and the bioactivity assessed by the DPPH assay. The chemical structures of the most active fractions were analyzed by nuclear magnetic resonance. Results The crude DCM extract of both the bee corn pollen and floral corn pollen provided the highest active free radical scavenging activity of the three solvent extracts, but it was significantly (over 28-fold higher in the bee corn pollen (EC50 = 7.42 ± 0.12 μg/ml, than the floral corn pollen (EC50 = 212 ± 13.6% μg/ml. After fractionation to homogeneity, the phenolic hydroquinone and the flavone 7-O-R-apigenin were found as the minor and major bioactive compounds, respectively. Bee corn pollen contained a reasonably diverse array of nutritional components, including

  19. Bioassay-guided isolation of active principles from Nigerian medicinal plants identifies new trypanocides with low toxicity and no cross-resistance to diamidines and arsenicals.

    Science.gov (United States)

    Ebiloma, Godwin Unekwuojo; Igoli, John Ogbaji; Katsoulis, Evangelos; Donachie, Anne-Marie; Eze, Anthonius; Gray, Alexander Ian; de Koning, Harry P

    2017-04-18

    Leaves from the plant species studied herein are traditionally used in northern Nigeria against various protozoan infections. However, none of these herbal preparations have been standardized, nor have their toxicity to mammalian cells been investigated. In search of improved and non-toxic active antiprotozoal principles that are not cross-resistant with current anti-parasitics, we here report the results of the in vitro screening of extracts from seven selected medicinal plant species (Centrosema pubescens, Moringa oleifera, Tridax procumbens, Polyalthia longifolia, Newbouldia laevis, Eucalyptus maculate, Jathropha tanjorensis), used traditionally to treat kinetoplastid infections in Nigeria, and the isolation of their bioactive principles. To investigate the efficacies of medicinal plant extracts, and of compounds isolated therefrom, against kinetoplastid parasites, assess cross-resistance to existing chemotherapy, and assay their toxicity against mammalian cells in vitro. Plants were extracted with hexane, ethyl acetate and methanol. Active principles were isolated by bioassay-led fractionation, testing for trypanocidal activity, and identified using NMR and mass spectrometry. EC 50 values for their activity against wild-type and multi-drug resistant Trypanosoma brucei were obtained using the viability indicator dye resazurin. Seven medicinal plants were evaluated for activity against selected kinetoplastid parasites. The result shows that crude extracts and isolated active compounds from Polyalthia longifolia and Eucalyptus maculata, in particular, display promising activity against drug-sensitive and multi-drug resistant Trypanosoma brucei. The EC 50 value of a clerodane (16α-hydroxy-cleroda-3,13(14)-Z-dien-15,16-olide) isolated from Polyalthia longifolia was as low as 0.38µg/mL, while a triterpenoid (3β,13β-dihydroxy-urs-11-en-28-oic acid) isolated from Eucalyptus maculata displayed an EC 50 of 1.58µg/mL. None of the isolated compounds displayed toxicity

  20. Quantitative evaluation of in vitro effects and interactions of active fractions in a Chinese medicinal formula (Yaotongning Capsule) on rat chondrocytes.

    Science.gov (United States)

    Zhang, Li-Guo; Ouyang, Xiao-Wen; Wu, Ting-Ting; Ni, Li-Jun; Shi, Wan-Zhong

    2014-09-29

    Yaotongning Capsule (YTNC) is a Traditional Chinese Medicinal (TCM) formula that has been demonstrated to be effective for osteoarthritis (OA) treatment in clinical use. Many compounds and 10 component medicinal materials (CMMs for short, i.e., the fundamental elements used in TCM formulas) in YTNC are challenging to study the pharmacological effects and interactions of the CMMs. Besides, it is difficult to know whether the YTNC formula is reasonable, and if YTNC formula could be improved without comparing YTNC with other TCM formulas of treating OA. Based on different combinations of the active fractions from the 10 CMMs of YTNC and eight additional herbs frequently used in the TCM formulas of treating OA, the present study evaluated systematically the in vitro effects of these active fractions and the interactions among the active fractions from YTNC on rat chondrocytes to find possible solutions of the above questions. Based on the formulation of YTNC and the concept of combinatorial chemistry, the active fractions were applied to form the whole YTNC prescription (i.e., the combination of all YTNC active fractions and the extract of YTNC׳s vehicle), five disassembled formulas of YTNC (i.e., the combinations of some active fractions in YTNC) and 21 TCM samples consisted of different kinds of active fractions. The degenerated chondrocytes were induced with interleukin-1β (IL-1β), and then the half-effective concentration (EC50) value of the proliferation activity was analyzed to evaluate the 27 TCM samples. Nine samples were screened for the following evaluation on glycosaminoglycan (GAG) synthesis. Rat articular cartilage was obtained from six Sprague-Dawley rats (seven days of age), and then chondrocytes were isolated through enzymatic digestion with 0.2% Collagenase II. Proliferations of chondrocytes were examined through Cell Counting Kit-8 assay, when the intracellular levels of GAG were detected by 1,9-Dimethylmethylene blue staining. The interactions

  1. Novel approach for the voltammetric evaluation of antioxidant activity using DPPH·-modified electrode

    International Nuclear Information System (INIS)

    Ziyatdinova, Guzel; Snegureva, Yulia; Budnikov, Herman

    2017-01-01

    Highlights: •Voltammetric characteristics of DPPH· immobilized on the electrode surface is studied. •DPPH·/CeO 2 -CPB/GCE gives reversible one electron highly sensitive radical reduction. •DPV on DPPH·/CeO 2 -CPB/GCE is developed for the antioxidants activity evaluation. •Natural phenolic antioxidants and medicinal herbs extracts are investigated. •Good agreement of DPV and standard method data is obtained. -- Abstract: The electrochemical behavior of 2,2-diphenyl-1-picrylhydrazyl (DPPH·) immobilized on the electrode surface has been studied. Bare glassy carbon electrode (GCE) and modified with dispersions of CeO 2 nanoparticles in water (CeO 2 -H 2 O/GCE) and cationic surfactant cetylpyridinium bromide medium (CeO 2 -CPB/GCE) has been investigated as a platform for the DPPH· immobilization. The best voltammetric characteristics (peak potential separation of 70 mV, system reversibility with currents ratio of 0.98 and the highest peaks currents) have been observed on CeO 2 -CPB/GCE. The effect of CeO 2 nanoparticles concentration has been evaluated. Scanning electron microscopy and electrochemical impedance spectroscopy have been applied for the electrode characterization. DPPH·/CeO 2 -CPB/GCE has been used for the estimation of the antioxidants activity of natural phenolic antioxidants (quercetin, tannin, catechin and ferulic acid) expressed as the EC 50 parameter according to differential pulse voltammetric (DPV) data. The EC 50 decreased in the following order: quercetin (29 ± 1 μM), tannin (29 ± 4 μM), catechin (117 ± 4 μM) and ferulic acid (731 ± 17 μM). These data are in a good agreement with the results of standard spectrophotometric determination. The developed approach has been successfully applied for the antioxidant activity evaluation of medicinal herbs tinctures, infusions and decoctions.

  2. Influence of cations on activity and distribution of protein kinase C in S49 lymphoma cells

    International Nuclear Information System (INIS)

    Brunton, L.; Watson, M.; Schultz, M.; Trejo, J.; Speizer, L.

    1987-01-01

    In S49 lymphoma cells, the distribution of protein kinase C (PKC) between soluble and membrane fractions can be regulated by the concentration of Ca ++ in the homogenization buffer. When cells are fractionated with 10μM Ca ++ and low Mg ++ (0.3mM), PKC is largely (56%) membrane-bound. Mg ++ inhibits this effect of Ca ++ by 75%; the EC 50 for Mg ++ reducing the translocation induced by 10μM Ca ++ is 1mM, as detected by binding of [ 3 H] phorbol dibutyrate ([ 3 H]PDB). Other divalent cations have different effects. When Cu ++ (1mM) is included in the homogenization buffer, both the enzymic activity of PKC and its capacity to bind [ 3 H]PDB are lost in both the cytosolic and membrane fractions. Cd ++ and Zn ++ (at 1mM) also inhibit the binding of [ 3 H]PDB to PKC in cytosolic fractions. K + , Li + , Co ++ and Mn ++ at 1mM do not mimic these effects. With Ca ++ at 500μM, the EC 50 for inhibition by Cu ++ of [ 3 H]PDB binding and enzymic activity of PKC are 25μM and 75μM, respectively. These effects of Cu ++ are also noticeable when the cation is added to intact S49 cells. The effect of Cu ++ on PKC is only relatively specific: [Cu ++ ] ≥ 100μM inhibits the activity of cyclic AMP-dependent protein kinase in vitro. Knowledge of these effects of heavy metals on PKC may prove helpful in manipulation of the enzyme pharmacologically as well as in determining the role of PKC in the cellular responses to heavy metals

  3. Appraisal of Total Phenol, Flavonoid Contents, and Antioxidant Potential of Folkloric Lannea coromandelica Using In Vitro and In Vivo Assays

    Directory of Open Access Journals (Sweden)

    Tekeshwar Kumar

    2015-01-01

    Full Text Available The aim of this study was to determine the impending antioxidant properties of different extracts of crude methanolic extract (CME of leaves of Lannea coromandelica (L. coromandelica and its two ethyl acetate (EAF and aqueous (AqF subfractions by employing various established in vitro systems and estimation of total phenolic and flavonoid content. The results showed that extract and fractions possessed strong antioxidant activity in vitro and among them, EAF had the strongest antioxidant activity. EAF was confirmed for its highest phenolic content, total flavonoid contents, and total antioxidant capacity. The EAF was found to show remarkable scavenging activity on 2,2-diphenylpicrylhydrazyl (DPPH (EC50 63.9 ± 0.64 µg/mL, superoxide radical (EC50 8.2 ± 0.12 mg/mL, and Fe2+ chelating activity (EC50 6.2 ± 0.09 mg/mL. Based on our in vitro results, EAF was investigated for in vivo antioxidant assay. Intragastric administration of the EAF can significantly increase levels of superoxide dismutase (SOD, catalase (CAT, glutathione (GSH, and glutathione peroxidase (GSH-Px levels, and decrease malondialdehyde (MDA content in the liver and kidney of CCl4-intoxicated rats. These new evidences show that L. coromandelica bared antioxidant activity.

  4. The satiety signaling neuropeptide perisulfakinin inhibits the activity of central neurons promoting general activity

    Directory of Open Access Journals (Sweden)

    Dieter Wicher

    2007-12-01

    Full Text Available The metabolic state is one of the determinants of the general activity level. Satiety is related to resting or sleep whereas hunger correlates to wakefulness and activity. The counterpart to the mammalian satiety signal cholecystokinin (CCK in insects are the sulfakinins. The aim of this study was to resolve the mechanism by which the antifeedant activity of perisulfakinin (PSK in Periplaneta americana is mediated. We identified the sources of PSK which is used both as hormone and as paracrine messenger. PSK is found in the neurohemal organ of the brain and in nerve endings throughout the central nervous system. To correlate the distributions of PSK and its receptor (PSKR, we cloned the gene coding for PSKR and provide evidence for its expression within the nervous system. It occurs only in a few neurons, among them are the dorsal unpaired median (DUM neurons which release octopamine thereby regulating the general level of activity. Application of PSK to DUM neurons attenuated the spiking frequency (EC50=11pM due to reduction of a pacemaker Ca2+ current through cAMP-inhibited pTRPγ channels. PSK increased the intracellular cAMP level while decreasing the intracellular Ca2+ concentration in DUM neurons. Thus, the satiety signal conferred by PSK acts antagonistically to the hunger signal, provided by the adipokinetic hormone (AKH: PSK depresses the electrical activity of DUM neurons by inhibiting the pTRPγ channel that is activated by AKH under conditions of food shortage.

  5. Activity of andrographolide against dengue virus.

    Science.gov (United States)

    Panraksa, Patcharee; Ramphan, Suwipa; Khongwichit, Sarawut; Smith, Duncan R

    2017-03-01

    Dengue is the most prevalent arthropod-transmitted viral illness of humans, with an estimated 100 million symptomatic infections occurring each year and more than 2.5 billion people living at risk of infection. There are no approved antiviral agents against dengue virus, and there is only limited introduction of a dengue vaccine in some countries. Andrographolide is derived from Andrographis paniculata, a medicinal plant traditionally used to treat a number of conditions including infections. The antiviral activity of andrographolide against dengue virus (DENV) serotype 2 was evaluated in two cell lines (HepG2 and HeLa) while the activity against DENV 4 was evaluated in one cell line (HepG2). Results showed that andrographolide had significant anti-DENV activity in both cell lines, reducing both the levels of cellular infection and virus output, with 50% effective concentrations (EC 50 ) for DENV 2 of 21.304 μM and 22.739 μM for HepG2 and HeLa respectively. Time of addition studies showed that the activity of andrographolide was confined to a post-infection stage. These results suggest that andrographolide has the potential for further development as an anti-viral agent for dengue virus infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Critical appraisal of respirometric methods for metal inhibition on activated sludge

    International Nuclear Information System (INIS)

    Cokgor, E. Ubay; Ozdemir, S.; Karahan, O.; Insel, G.; Orhon, D.

    2007-01-01

    This paper evaluates the merit of oxygen uptake rate measurements for the assessment of metal inhibition on activated sludge. For this purpose, experiments are conducted to calculate EC 50 levels of nickel and hexavalent chromium using the ISO 8192 procedure, yielding results that are highly variable and difficult to correlate, depending on the type of substrate and the initial food to microorganism ratio. Similar experiments based on continuous respirometric measurements to give the entire oxygen uptake rate profile provide a much better insight on the impact of inhibition on different biochemical processes taking place in the reactor. The results indicate that percent reduction of the amount of dissolved oxygen utilized after an appropriate reaction time is a much better index for the assessment of the inhibitory effects

  7. Effect of radiation processing on the antioxidant activity of Sage and Cinnamon

    International Nuclear Information System (INIS)

    El-Niley, H. F. G.; Farag, M. D. H.

    2012-12-01

    In the present study, the effect of radiation processing on dried sage leaves and cinnamon barks samples were carried out at dose level of 25 kGy. Total phenolic content was determined in the extracts of these herbs alongside the antioxidant properties of their methanoic extracts were assessed using reducing power assay and by DPPH radical test within an extract concentration range 2.5 to 40 mg/ml of methanol. The result showed the total phenolic compounds were increased by 11.18% and 10.19% for irradiated sage and cinnamon, respectively. The values of EC 50 estimated from the results of reducing power assay and DPPH radical test showed the sage extracts had higher antioxidant activity tham cinnamon extracts. In summary, gamma- irradiation of dried sage leaves and cinnamon barks was found to be significantly increase the antioxidant properties of dried sage leaves and cinnamon barks but also enhanced the antioxidant properties, to some extent. (Author)

  8. Antioxidant activity and chemical components as potential anticancer agents in the olive leaf (Olea europaea L. cv Leccino.) decoction.

    Science.gov (United States)

    De Marino, Simona; Festa, Carmen; Zollo, Franco; Nini, Antonella; Antenucci, Lina; Raimo, Gennaro; Iorizzi, Maria

    2014-01-01

    Epidemiological studies have shown that a reduced risk of chronic diseases such as cancer and cardiovascular diseases is correlated with a regular consumption of fruits and vegetable, many of which are rich in polyphenols. The additive and synergistic effect of phytochemicals in fruits and vegetables may reduce chronic diseases related to oxidative stress in human body. Olea europaea L. leaf are rich in phenolic components, which have been proposed to play a role in cancer prevention. The purpose of this study was to identify the main components in the Olea europaea L. leaf (cv. Leccino) preserved during the decoction preparation, in order to delineate the antioxidant activities of the crude extracts and its isolated compounds by using different in vitro assays including DPPH radicalscavenging capacity, total antioxidant capacity (TAC), xanthine oxidase (XO) inhibitory effect and the ability to delay the linoleic acid peroxidation process (ALP). The aqueous decoction was partitioned obtaining four extracts and the n-butanol extract showed the highest antioxidant activity and the highest total phenolic content. Phytochemical investigation leads to the isolation of thirteen secondary metabolites including simple phenolics, flavonoids, secoiridoids whose structures were elucidated by spectroscopic data (1D and 2D NMR) and spectrometric techniques. A significant free radical scavenging effect against DPPH has been evidenced in fraxamoside (1) (EC50 62.6 µM) and taxifolin (5) (EC50 50.0 µM), isolated for the first time from the water decoction. The most active compound in the TAC evaluation, was the 3,4 dihydro-phenyl glycol (8) (0.90 caffeic acid equiv.) while taxifolin and fraxamoside resulted as the most efficient inhibitors of XO activity (IC50 2.7 and 5.2 µM, respectively). Secoxyloganin (4), oleuropein (2) and tyrosol (6) showed the highest ALP activity. This study adds to the growing body of data supporting the bioactivities of phytochemicals and their

  9. Isolation and molecular identification of a UV-resistant strain of Dietzia maris and antioxidant activity of pigment

    Directory of Open Access Journals (Sweden)

    Narges Zamanian

    2016-09-01

    Full Text Available Introduction: The ability of radioresistant bacteria to survive high levels of UV radiation has been linked to their strong DNA repair systems and ability to produce primary and secondary metabolic products. The biosynthesis of pigments provides an opportunity for bacteria to live in radiation-rich environment. Recent radiation-responsive pigments are used commercially as food colorants, anticancer drugs, as well as antibiotics and for cosmetic purposes. Materials and methods: Soil sample of Omidiyeh city was collected during the spring of 2014 and UV-resistant strain was isolated after primary and secondary screening. Then it was identified by molecular methods (16S rRNA gene sequencing. Antioxidant activity of pigment was evaluated by 2,2 -diphenyl-1-picryl hydrazyl (DPPH and the reducing power of pigments were analyzed by ferric chloride. Results: In this present study, new UV-resistant strain NM2 was isolated and by comparison of these 16S rRNA gene sequences to public database using the BLAST, the genus and species of the isolate was identified as Dietzia maris with 99% similarity. Extraction of pigment from isolated strain was carried out by methanol and acetone as solvents. The spectrum is characterized by maximum peak at 473 nm for pigment of NM2 strain. Antioxidant activity and the reducing ability of pigments increased by increasing their concentrations. NM2 strain pigment showed EC50 concentration of 3.30 mg/ml for DPPH free radical scavenging activity, and EC50 concentration of 28.46 µg/ml for reducing power. Discussion and conclusion: Isolation of natural resources of pigment is very important with high anti-oxidant activity. In the current study, pigment of UV-resistant bacteria demonstrated a strong antioxidant activity in vitro and pigment of these bacteria could play an important role in UV tolerance. Pigment of UV-resistant bacteria may be an appropriate source for antioxidative-related functional foods and the pharmaceutical

  10. Inhibitors of plasmodial serine hydroxymethyltransferase (SHMT): cocrystal structures of pyrazolopyrans with potent blood- and liver-stage activities.

    Science.gov (United States)

    Witschel, Matthias C; Rottmann, Matthias; Schwab, Anatol; Leartsakulpanich, Ubolsree; Chitnumsub, Penchit; Seet, Michael; Tonazzi, Sandro; Schwertz, Geoffrey; Stelzer, Frank; Mietzner, Thomas; McNamara, Case; Thater, Frank; Freymond, Céline; Jaruwat, Aritsara; Pinthong, Chatchadaporn; Riangrungroj, Pinpunya; Oufir, Mouhssin; Hamburger, Matthias; Mäser, Pascal; Sanz-Alonso, Laura M; Charman, Susan; Wittlin, Sergio; Yuthavong, Yongyuth; Chaiyen, Pimchai; Diederich, François

    2015-04-09

    Several of the enzymes related to the folate cycle are well-known for their role as clinically validated antimalarial targets. Nevertheless for serine hydroxymethyltransferase (SHMT), one of the key enzymes of this cycle, efficient inhibitors have not been described so far. On the basis of plant SHMT inhibitors from an herbicide optimization program, highly potent inhibitors of Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) SHMT with a pyrazolopyran core structure were identified. Cocrystal structures of potent inhibitors with PvSHMT were solved at 2.6 Å resolution. These ligands showed activity (IC50/EC50 values) in the nanomolar range against purified PfSHMT, blood-stage Pf, and liver-stage P. berghei (Pb) cells and a high selectivity when assayed against mammalian cell lines. Pharmacokinetic limitations are the most plausible explanation for lack of significant activity of the inhibitors in the in vivo Pb mouse malaria model.

  11. Free radical scavenging activity of ethanolic extracts from herbs and spices commercialized in Brazil

    Directory of Open Access Journals (Sweden)

    Lilian Regina Barros Mariutti

    2008-12-01

    Full Text Available Ethanolic extracts from 23 different dried herbs and spices commercialized in Brazil were investigated for their free radical scavenging properties using the stable free radicals 2,2'-diphenyl-β-picrylhydrazyl (DPPH• and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS•+, and Trolox as reference (TEAC for both radicals. The kinetic curves for both radicals showed to follow the first order kinetics model and the decay rate constant (k obs was calculated. For all the samples, the two methods showed a good linear TEAC correlation, indicating that the average reactivity of the compounds present in the ethanolic extracts was similar. Sage and rosemary extracts showed the highest free radical scavenging capacities, while onion showed negligible activity and colorifico, one of the most consumed spices in Brazil, showed low ABTS•+ scavenging activity. Three distinct situations were found for the extracts concerning the DPPH• scavenging capacities: (1 extracts, like rosemary and laurel, that presented the same efficient concentrations (EC50 but differed in the TEAC values and velocities of action (k obs, (2 extracts, such as garlic and basil, that showed similar EC50 and TEAC values, but different k obs values and (3 extracts that reacted at the same velocities but completely differed in the free radical scavenging capacities, like black pepper, savory, nutmeg, rosemary and sage. Similar considerations could be done for the ABTS•+ results. For the first time the ABTS•+ scavenging activity for allspice, basil, cardamom, chives, colorifico, cumin, dill, laurel, marjoram, parsley and tarragon was reported.Extratos etanólicos de 23 ervas e condimentos desidratados comercializados no Brasil foram analisados quanto as suas propriedades antioxidantes utilizando os radicais 2,2'-difenil-β-picrilhidrazil (DPPH• e ácido 2,2'-azino-bis(3-etilbenzotiazolina-6-sulfônico (ABTS•+, Trolox foi usado como referência para ambos radicais

  12. Isoprenylated flavonoids from the root bark of Morus alba and their hepatoprotective and neuroprotective activities.

    Science.gov (United States)

    Jung, Jae-Woo; Ko, Won-Min; Park, Ji-Hae; Seo, Kyeong-Hwa; Oh, Eun-Ji; Lee, Dae-Young; Lee, Dong-Sung; Kim, Youn-Chul; Lim, Dong-Wook; Han, Daeseok; Baek, Nam-In

    2015-11-01

    A new isoprenylated flavonoid, 2S-5,7,2',4'-tetrahydroxy-3',5'-di-(γ,γ-dimethylallyl)flavanone, sanggenol Q (1), along with seven known isoprenylated flavonoids, sanggenol A (2), sanggenol L (3), kuwanon T (4), cyclomorusin (5), sanggenon F (6), sanggenol O (7), and sanggenon N (8), three known Diels-Alder type adducts, sanggenon G (9), mulberrofuran G (10), and mulberrofuran C (11), and a known benzofuran, moracin E (12), were isolated from the root bark of Morus alba using silica gel, ODS, and Sephadex LH-20 column chromatography. Chemical structures were determined based on spectroscopic data analyses including NMR, MS, CD, and IR. For the first time, compounds 1 and 7 were isolated from the root bark of M. alba. All compounds were evaluated for hepatoprotective activity on t-BHP-induced oxidative stress in HepG2 cells and neuroprotective activity on glutamate-induced cell death in HT22 cells. Compounds 1, 4, 8, 10, and 11 showed protective effects on t-BHP-induced oxidative stress with EC50 values of 6.94 ± 0.38, 30.32 ± 6.82, 23.45 ± 4.72, 15.31 ± 2.21, and 0.41 ± 0.48 μM, respectively, and compounds 1, 2, 10, 11, and 12 showed protective effects on glutamate-induced cell death with EC50 values of 5.54 ± 0.86, 34.03 ± 7.71, 19.71 ± 0.71, 16.50 ± 7.82, and 1.02 ± 0.13 μM, respectively.

  13. The antipsychotic drug loxapine is an opener of the sodium-activated potassium channel slack (Slo2.2).

    Science.gov (United States)

    Biton, B; Sethuramanujam, S; Picchione, Kelly E; Bhattacharjee, A; Khessibi, N; Chesney, F; Lanneau, C; Curet, O; Avenet, P

    2012-03-01

    Sodium-activated potassium (K(Na)) channels have been suggested to set the resting potential, to modulate slow after-hyperpolarizations, and to control bursting behavior or spike frequency adaptation (Trends Neurosci 28:422-428, 2005). One of the genes that encodes K(Na) channels is called Slack (Kcnt1, Slo2.2). Studies found that Slack channels were highly expressed in nociceptive dorsal root ganglion neurons and modulated their firing frequency (J Neurosci 30:14165-14172, 2010). Therefore, Slack channel openers are of significant interest as putative analgesic drugs. We screened the library of pharmacologically active compounds with recombinant human Slack channels expressed in Chinese hamster ovary cells, by using rubidium efflux measurements with atomic absorption spectrometry. Riluzole at 500 μM was used as a reference agonist. The antipsychotic drug loxapine and the anthelmintic drug niclosamide were both found to activate Slack channels, which was confirmed by using manual patch-clamp analyses (EC(50) = 4.4 μM and EC(50) = 2.9 μM, respectively). Psychotropic drugs structurally related to loxapine were also evaluated in patch-clamp experiments, but none was found to be as active as loxapine. Loxapine properties were confirmed at the single-channel level with recombinant rat Slack channels. In dorsal root ganglion neurons, loxapine was found to behave as an opener of native K(Na) channels and to increase the rheobase of action potential. This study identifies new K(Na) channel pharmacological tools, which will be useful for further Slack channel investigations.

  14. Biochemical Characterization and Antimicrobial and Antifungal Activity of Two Endemic Varieties of Garlic (Allium sativum L.) of the Campania Region, Southern Italy.

    Science.gov (United States)

    Fratianni, Florinda; Riccardi, Riccardo; Spigno, Patrizia; Ombra, Maria Neve; Cozzolino, Autilia; Tremonte, Patrizio; Coppola, Raffaele; Nazzaro, Filomena

    2016-07-01

    Extracts of the bulbs of the two endemic varieties "Rosato" and "Caposele" of Allium sativum of the Campania region, Southern Italy, were analyzed. The phenolic content, ascorbic acid, allicin content, and in vitro antimicrobial and antifungal activity were determined. Ultra performance liquid chromatography with diode array detector performed polyphenol profile. The polyphenolic extracts showed antioxidant activity (EC50) lower than 120 mg. The amount of ascorbic acid and allicin in the two extracts was similar. Polyphenol extract exhibited antimicrobial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and (only by the extract of Rosato) against Bacillus cereus. The extract of Caposele was more effective in inhibiting the growth of Aspergillus versicolor and Penicillum citrinum. On the other hand, the extract of Rosato was effective against Penicillium expansum.

  15. Phytochemical screening, total phenolics and antioxidant activities of bark and leaf extracts of Goniothalamus velutinus (Airy Shaw from Brunei Darussalam

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    Erum Iqbal

    2015-07-01

    Full Text Available Goniothalamus velutinus Airy Shaw belongs to the family Annonaceae which is known to have anticancer, antitumor and many other bioactivities. Natives of Sabah and Sarawak use root decoction of G. velutinus for the treatment of headache and food poisoning while the bark was used as a mosquito repellent. Bark and leaf extracts of this plant, obtained from Brunei Darussalam, were tested for phytochemical and antioxidant activities. Phytochemical screening of plant extracts revealed the presence of alkaloids, steroids, terpenoids and cardiac glycosides. Quantitative determination of total phenolics, total flavonoids, and various in vitro antioxidant activities (DPPH, ABTS and FRAP of methanolic extract was carried out using colorimetric methods. The total phenolic content, expressed as mg of gallic acid equivalent (GAE per gram of extract, was found to be 68 mg GAE/g and 78 mg GAE/g for bark and leaves respectively. The radical scavenging activity measurement, expressed in terms of EC50 (effective concentration of extract in μg/mL that reduces DPPH absorbance to 50% as compared to negative control, for leaf and bark extracts was found to be 155 μg/mL and 204 μg/mL respectively. Standards trolox and ascorbic acid show EC50 value of 5 μg/mL and 4 μg/mL respectively. Trolox equivalent antioxidant capacity (TEAC was measured using the ABTS and FRAP method. Result for bark and leaf extracts was 79 mg and 106 mg trolox equivalent (TE/g respectively for the ABTS method. For FRAP assay, results for bark and leaf extracts were 80 and 89 mg TE/g respectively.

  16. Assessment of Cu applications in two contrasting soils-effects on soil microbial activity and the fungal community structure.

    Science.gov (United States)

    Keiblinger, Katharina M; Schneider, Martin; Gorfer, Markus; Paumann, Melanie; Deltedesco, Evi; Berger, Harald; Jöchlinger, Lisa; Mentler, Axel; Zechmeister-Boltenstern, Sophie; Soja, Gerhard; Zehetner, Franz

    2018-03-01

    Copper (Cu)-based fungicides have been used in viticulture to prevent downy mildew since the end of the 19th century, and are still used today to reduce fungal diseases. Consequently, Cu has built up in many vineyard soils, and it is still unclear how this affects soil functioning. The present study aimed to assess the short and medium-term effects of Cu contamination on the soil fungal community. Two contrasting agricultural soils, an acidic sandy loam and an alkaline silt loam, were used for an eco-toxicological greenhouse pot experiment. The soils were spiked with a Cu-based fungicide in seven concentrations (0-5000 mg Cu kg -1 soil) and alfalfa was grown in the pots for 3 months. Sampling was conducted at the beginning and at the end of the study period to test Cu toxicity effects on total microbial biomass, basal respiration and enzyme activities. Fungal abundance was analysed by ergosterol at both samplings, and for the second sampling, fungal community structure was evaluated via ITS amplicon sequences. Soil microbial biomass C as well as microbial respiration rate decreased with increasing Cu concentrations, with EC 50 ranging from 76 to 187 mg EDTA-extractable Cu kg -1 soil. Oxidative enzymes showed a trend of increasing activity at the first sampling, but a decline in peroxidase activity was observed for the second sampling. We found remarkable Cu-induced changes in fungal community abundance (EC 50 ranging from 9.2 to 94 mg EDTA-extractable Cu kg -1 soil) and composition, but not in diversity. A large number of diverse fungi were able to thrive under elevated Cu concentrations, though within the order of Hypocreales several species declined. A remarkable Cu-induced change in the community composition was found, which depended on the soil properties and, hence, on Cu availability.

  17. Pereskia aculeata Muller (Cactaceae Leaves: Chemical Composition and Biological Activities

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    Lucèia Fàtima Souza

    2016-09-01

    Full Text Available The aims of this work were to study the chemical composition of the essential oil from the leaves of Pereskia aculeata and to evaluate some biological activities of three leaf extracts. The phenolic content, antioxidant activity, and in vitro antimicrobial and antifungal activities were determined. The methanol extract showed antioxidant activity (EC50 7.09 mg/mL and high polyphenols content (15.04 ± 0.31 mg gallic acid equivalents (GAE/g. The petroleum ether extract exhibited potent antibacterial activity against Escherichia coli, whereas the chloroform extract showed inhibitory activity against Bacillus cereus and Staphylococcus aureus. The petroleum ether and methanol extracts were more effective in inhibiting the growth of Aspergillus versicolor. The possible cytotoxicity of extracts on neuroblastoma SH-SY5Y cancer cell line and the influence on adenylate cyclase (ADCY expression was also studied. P. aculeata chloroform extract showed antiproliferative activity with an IC50 value of 262.83 µg/mL. Treatments of SH-SY5Y neuroblastoma cells with 100 µg/mL of methanol extract significantly reduced ADCY1 expression.

  18. Pereskia aculeata Muller (Cactaceae) Leaves: Chemical Composition and Biological Activities.

    Science.gov (United States)

    Souza, Lucèia Fàtima; Caputo, Lucia; Inchausti De Barros, Ingrid Bergman; Fratianni, Florinda; Nazzaro, Filomena; De Feo, Vincenzo

    2016-09-03

    The aims of this work were to study the chemical composition of the essential oil from the leaves of Pereskia aculeata and to evaluate some biological activities of three leaf extracts. The phenolic content, antioxidant activity, and in vitro antimicrobial and antifungal activities were determined. The methanol extract showed antioxidant activity (EC50 7.09 mg/mL) and high polyphenols content (15.04 ± 0.31 mg gallic acid equivalents (GAE)/g). The petroleum ether extract exhibited potent antibacterial activity against Escherichia coli, whereas the chloroform extract showed inhibitory activity against Bacillus cereus and Staphylococcus aureus. The petroleum ether and methanol extracts were more effective in inhibiting the growth of Aspergillus versicolor. The possible cytotoxicity of extracts on neuroblastoma SH-SY5Y cancer cell line and the influence on adenylate cyclase (ADCY) expression was also studied. P. aculeata chloroform extract showed antiproliferative activity with an IC50 value of 262.83 µg/mL. Treatments of SH-SY5Y neuroblastoma cells with 100 µg/mL of methanol extract significantly reduced ADCY1 expression.

  19. Novel biotransformation process of podophyllotoxin to 4 β-sulfur-substituted podophyllum derivates with anti-tumor activity by Penicillium purpurogenum Y.J. Tang.

    Science.gov (United States)

    Bai, J-K; Zhao, W; Li, H-M; Tang, Y-J

    2012-01-01

    According to the structure-function relationship of podophyllotoxin (PTOX) and its analogue of 4'- demethylepipodophyllotoxin (DMEP), the 4 β-substitution of sulfur-containing heterocyclic compounds with a carbon-sulfur bond at 4 position of PTOX or DMEP is an essential modification direction for improving the anti-tumor activity. So, four novel 4 β-sulfursubstituted podophyllum derivatives (i.e., 4β -(1,2,4-triazole-3-yl)sulfanyl-4-deoxy-podophyllotoxin (4-MT-PTOX), 4β-(1,3,4- thiadiazole-2-yl)sulfanyl-4-deoxy-podophyllotoxin (4-MTD-PTOX), 4β-(1,2,4-triazole-3-yl)sulfanyl-4-deoxy-4' -demethylepipodophyllotoxin (4-MT-DMEP), and 4β-(1,3,4-thiadiazole-2-yl)sulfanyl-4-deoxy-4'-demethylepipodophyllotoxin (4-MTD-DMEP)) were designed and then successfully biosynthesized in this work. In the novel sulfur-substituted biotransformation processes, PTOX and DMEP was linked with sulfur-containing compounds (i.e., 3-mercapto-1,2,4-triazole (MT) and 2-mercapto-1,3,4-thiadiazole (MTD)) at 4 position of cycloparaffin to produce 4-MT-PTOX (1), 4-MTD-PTOX (2), 4-MT-DMEP (3), and 4-MTD-DMEP (4) by Penicillium purpurogenum Y.J. Tang, respectively, which was screened out from Diphylleia sinensis Li (Hubei, China). All the novel compounds exhibited promising in vitro bioactivity, especially 4-MT-PTOX (1). Compared with etoposide (i.e., a 50 % effective concentration [EC(50)] of 25.72, 167.97, and 1.15 M), the EC(50) values of 4-MT-PTOX (1) against tumor cell line BGC-823, A549 and HepG2 (i.e., 0.28, 0.76, and 0.42 M) were significantly improved by 91, 221 and 2.73 times, respectively. Moreover, the EC(50) value of 4-MT-PTOX (1) against the normal human cell line HK-2 (i.e., 182.4 μM) was 19 times higher than that of etoposide (i.e., 9.17 μM). Based on the rational design, four novel 4 β-sulfur-substituted podophyllum derivatives with superior in vitro anti-tumor activity were obtained for the first time. The correctness of structure-function relationship and rational drug

  20. In Vitro Antimicrobial and Antioxidant Activities of Ethanolic Extract of Lyophilized Mycelium of Pleurotus ostreatus PQMZ91109

    Directory of Open Access Journals (Sweden)

    Emanuel Vamanu

    2012-03-01

    Full Text Available The antioxidant and antimicrobial potential of the ethanolic extract of Pleurotus ostreatus PQMZ91109 mycelium was determined based on inorganic and organic nitrogen sources in the culture medium. The presence of ammonium sulfate resulted in a greater accumulation of bioactive compounds compared with the organic ones. This finding was also confirmed by the low values of the ascertained EC50 and minimum inhibitory concentration (MICs. Among the organic sources, peptone followed by corn extract, led to a more important radical-scavenging activity. The extracts selectively inhibited the tested strains, mainly the two of the genus Candida, at an MIC value of 1.25 mg/mL. The antioxidant potential was evaluated by the inhibition capacity of the 2,2-diphenyl-1-picrylhydrazyl (DPPH radical, β-carotene-linoleic acid, which is the reducing power. In addition, the quantity of the compounds with antioxidant effects confirmed the data obtained, they being present in the extracts.

  1. Synthesis of a Bicyclic Azetidine with In Vivo Antimalarial Activity Enabled by Stereospecific, Directed C(sp3)-H Arylation.

    Science.gov (United States)

    Maetani, Micah; Zoller, Jochen; Melillo, Bruno; Verho, Oscar; Kato, Nobutaka; Pu, Jun; Comer, Eamon; Schreiber, Stuart L

    2017-08-16

    The development of new antimalarial therapeutics is necessary to address the increasing resistance to current drugs. Bicyclic azetidines targeting Plasmodium falciparum phenylalanyl-tRNA synthetase comprise one promising new class of antimalarials, especially due to their activities against three stages of the parasite's life cycle, but a lengthy synthetic route to these compounds may affect the feasibility of delivering new therapeutic agents within the cost constraints of antimalarial drugs. Here, we report an efficient synthesis of antimalarial compound BRD3914 (EC 50 = 15 nM) that hinges on a Pd-catalyzed, directed C(sp 3 )-H arylation of azetidines at the C3 position. This newly developed protocol exhibits a broad substrate scope and provides access to valuable, stereochemically defined building blocks. BRD3914 was evaluated in P. falciparum-infected mice, providing a cure after four oral doses.

  2. Anthelmintic properties of traditional African and Caribbean medicinal plants: identification of extracts with potent activity against Ascaris suum in vitro

    Directory of Open Access Journals (Sweden)

    Williams Andrew R.

    2016-01-01

    Full Text Available Ascariasis affects more than 1 billion people worldwide, mainly in developing countries, causing substantial morbidity. Current treatments for Ascaris infection are based on mass drug administration (MDA with synthetic anthelmintic drugs such as albendazole, however continual re-infection and the threat of drug resistance mean that complementary treatment options would be highly valuable. Here, we screened ethanolic extracts from 29 medicinal plants used in Africa (Ghana and the Caribbean (US Virgin Islands for in vitro anthelmintic properties against Ascaris suum, a swine parasite that is very closely related to the human A. lumbricoides. A wide variety of activities were seen in the extracts, from negligible to potent. Extracts from Clausena anisata, Zanthoxylum zanthoxyloides and Punica granatum were identified as the most potent with EC50 values of 74, 97 and 164 μg/mL, respectively. Our results encourage further investigation of their use as complementary treatment options for ascariasis, alongside MDA.

  3. Evaluation of the Toxicity, AChE Activity and DNA Damage Caused by Imidacloprid on Earthworms, Eisenia fetida.

    Science.gov (United States)

    Wang, Kai; Qi, Suzhen; Mu, Xiyan; Chai, Tingting; Yang, Yang; Wang, Dandan; Li, Dongzhi; Che, Wunan; Wang, Chengju

    2015-10-01

    Imidacloprid is a well-known pesticide and it is timely to evaluate its toxicity to earthworms (Eisenia fetida). In the present study, the effect of imidacloprid on reproduction, growth, acetylcholinesterase (AChE) and DNA damage in earthworms was assessed using an artificial soil medium. The median lethal concentration (LC50) and the median number of hatched cocoons (EC50) of imidacloprid to earthworms was 3.05 and 0.92 mg/kg respectively, the lowest observed effect concentration of imidacloprid about hatchability, growth, AChE activity and DNA damage was 0.02, 0.5, 0.1 and 0.5 mg/kg, respectively.

  4. In vitro antiviral activity of plant extracts from Asteraceae medicinal plants.

    Science.gov (United States)

    Visintini Jaime, María F; Redko, Flavia; Muschietti, Liliana V; Campos, Rodolfo H; Martino, Virginia S; Cavallaro, Lucia V

    2013-07-27

    Due to the high prevalence of viral infections having no specific treatment and the constant appearance of resistant viral strains, the development of novel antiviral agents is essential. The aim of this study was to evaluate the antiviral activity against bovine viral diarrhea virus, herpes simplex virus type 1 (HSV-1), poliovirus type 2 (PV-2) and vesicular stomatitis virus of organic (OE) and aqueous extracts (AE) from: Baccharis gaudichaudiana, B. spicata, Bidens subalternans, Pluchea sagittalis, Tagetes minuta and Tessaria absinthioides. A characterization of the antiviral activity of B. gaudichaudiana OE and AE and the bioassay-guided fractionation of the former and isolation of one active compound is also reported. The antiviral activity of the OE and AE of the selected plants was evaluated by reduction of the viral cytopathic effect. Active extracts were then assessed by plaque reduction assays. The antiviral activity of the most active extracts was characterized by evaluating their effect on the pretreatment, the virucidal activity and the effect on the adsorption or post-adsorption period of the viral cycle. The bioassay-guided fractionation of B. gaudichaudiana OE was carried out by column chromatography followed by semipreparative high performance liquid chromatography fractionation of the most active fraction and isolation of an active compound. The antiviral activity of this compound was also evaluated by plaque assay. B. gaudichaudiana and B. spicata OE were active against PV-2 and VSV. T. absinthioides OE was only active against PV-2. The corresponding three AE were active against HSV-1. B. gaudichaudiana extracts (OE and AE) were the most selective ones with selectivity index (SI) values of 10.9 (PV-2) and > 117 (HSV-1). For this reason, both extracts of B. gaudichaudiana were selected to characterize their antiviral effects. Further bioassay-guided fractionation of B. gaudichaudiana OE led to an active fraction, FC (EC50 = 3.1 μg/ml; SI = 37

  5. Trigocherrierin A, a Potent Inhibitor of Chikungunya Virus Replication

    Directory of Open Access Journals (Sweden)

    Mélanie Bourjot

    2014-03-01

    Full Text Available Trigocherrierin A (1 and trigocherriolide E (2, two new daphnane diterpenoid orthoesters (DDOs, and six chlorinated analogues, trigocherrins A, B, F and trigocherriolides A–C, were isolated from the leaves of Trigonostemon cherrieri. Their structures were identified by mass spectrometry, extensive one- and two-dimensional NMR spectroscopy and through comparison with data reported in the literature. These compounds are potent and selective inhibitors of chikungunya virus (CHIKV replication. Among the DDOs isolated, compound 1 exhibited the strongest anti-CHIKV activity (EC50 = 0.6 ± 0.1 µM, SI = 71.7.

  6. Design, Synthesis and Fungicidal Activities of Some Novel Pyrazole Derivatives

    Directory of Open Access Journals (Sweden)

    Xue-Ru Liu

    2014-09-01

    Full Text Available In order to discover new compounds with good fungicidal activities, 32 pyrazole derivatives were designed and synthesized. The structures of the target compounds were confirmed by 1H-NMR, 13C-NMR, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS, and their fungicidal activities against Botrytis cinerea, Rhizoctonia solani Kuhn, Valsa mali Miyabe et Yamada, Thanatephorus cucumeris (Frank Donk, Fusarium oxysporum (S-chl f.sp. cucumerinum Owen, and Fusarium graminearum Schw were tested. The bioassay results indicated that most of the derivatives exhibited considerable antifungal activities, especially compound 26 containing a p-trifluoromethyl- phenyl moiety showed the highest activity, with EC50 values of 2.432, 2.182, 1.787, 1.638, 6.986, and 6.043 μg/mL against B. cinerea, R. solani, V. mali, T. cucumeris, F. oxysporum, and F. graminearum, respectively. Moreover, the activities of compounds such as compounds 27–32 were enhanced by introducing isothiocyanate and carboxamide moieties to the 5-position of the pyrazole ring.

  7. Chemical composition and antioxidant activity of two strawberry cultivars

    Directory of Open Access Journals (Sweden)

    Đilas Sonja M.

    2011-01-01

    Full Text Available The macro- and micro-chemical composition, as well as antioxidant activity of two strawberry cultivars, Marmolada and Clery, were studied. Results showed a noticeable difference in the sugar, protein and pectin contents. Clery had 6.92% and Marmolada 4.93% of total sugar. Also, protein and pectin contents were higher in the Clery cultivar. No significant difference was observed in acidity, as well as in ash and cellulose content. Marmolada had a higher content of total phenolics and flavonoids (228.04 mg GAE /100 g FW and 136.01 mg RE/100 g FW, respectively . The anthocyanins content in Marmolada (32.0 mg CGE/100 g FW was slightly lower than in Clery (36.0 mg CGE/100 g FW. The antioxidant activity was evaluated spectrophotometrically, using 2,2-diphenyl- 1-picrylhydrazyl (DPPH radical scavenging activity assay. The DPPH free radical scavenging activity, expressed as EC50 value, of Marmolada (0.77 mg/ml was higher than of Clery (0.83 mg/ml. There was a significant positive correlation (R2>0.90 between the concentration of phenolics/flavonoids/anthocyanins and DPPH radical scavenging activity of both strawberry cultivars. These results also showed that the antioxidant value of 100 g FW Marmolada and Clery is equivalent to 237.91 mg and 219.01 mg of vitamin C, respectively.

  8. Antifungal activity, main active components and mechanism of Curcuma longa extract against Fusarium graminearum

    Science.gov (United States)

    Zhang, Fusheng; Chen, Qin; Chen, Cheng; Yu, Xiaorui; Liu, Qingya; Bao, Jinku

    2018-01-01

    Curcuma longa possesses powerful antifungal activity, as demonstrated in many studies. In this study, the antifungal spectrum of Curcuma longa alcohol extract was determined, and the resulting EC50 values (mg/mL) of its extract on eleven fungi, including Fusarium graminearum, Fusarium chlamydosporum, Alternaria alternate, Fusarium tricinctum, Sclerotinia sclerotiorum, Botrytis cinerea, Fusarium culmorum, Rhizopus oryzae, Cladosporium cladosporioides, Fusarium oxysporum and Colletotrichum higginsianum, were 0.1088, 0.1742, 0.1888, 0.2547, 0.3135, 0.3825, 0.4229, 1.2086, 4.5176, 3.8833 and 5.0183, respectively. Among them, F. graminearum was selected to determine the inhibitory effects of the compounds (including curdione, isocurcumenol, curcumenol, curzerene, β-elemene, curcumin, germacrone and curcumol) derived from Curcuma longa. In addition, the antifungal activities of curdione, curcumenol, curzerene, curcumol and isocurcumenol and the synergies of the complexes of curdione and seven other chemicals were investigated. Differential proteomics of F. graminearum was also compared, and at least 2021 reproducible protein spots were identified. Among these spots, 46 were classified as differentially expressed proteins, and these proteins are involved in energy metabolism, tRNA synthesis and glucose metabolism. Furthermore, several fungal physiological differences were also analysed. The antifungal effect included fungal cell membrane disruption and inhibition of ergosterol synthesis, respiration, succinate dehydrogenase (SDH) and NADH oxidase. PMID:29543859

  9. Comparison of hippocampal G protein activation by 5-HT(1A) receptor agonists and the atypical antipsychotics clozapine and S16924.

    Science.gov (United States)

    Newman-Tancredi, A; Rivet, J-M; Cussac, D; Touzard, M; Chaput, C; Marini, L; Millan, M J

    2003-09-01

    This study employed [(35)S]guanosine 5'- O-(3-thiotriphosphate) ([(35)S]GTPgammaS) binding to compare the actions of antipsychotic agents known to stimulate cloned, human 5-HT(1A) receptors with those of reference agonists at postsynaptic 5-HT(1A) receptors. In rat hippocampal membranes, the following order of efficacy was observed (maximum efficacy, E(max), values relative to 5-HT=100): (+)8-OH-DPAT (85), flesinoxan (62), eltoprazine (60), S14506 (59), S16924 (48), buspirone (41), S15535 (22), clozapine (22), ziprasidone (21), pindolol (7), p-MPPI (0), WAY100,635 (0), spiperone (0). Despite differences in species and tissue source, the efficacy and potency (pEC(50)) of agonists (with the exception of clozapine) correlated well with those determined previously at human 5-HT(1A) receptors expressed in Chinese hamster ovary (CHO) cells. In contrast, clozapine was more potent at hippocampal membranes. The selective antagonists p-MPPI and WAY100,635 abolished stimulation of binding by (+)8-OH-DPAT, clozapine and S16924 (p-MPPI), indicating that these actions were mediated specifically by 5-HT(1A) receptors. Clozapine and S16924 also attenuated 5-HT- and (+)8-OH-DPAT-stimulated [(35)S]GTPgammaS binding, consistent with partial agonist properties. In [(35)S]GTPgammaS autoradiographic studies, 5-HT-induced stimulation, mediated through 5-HT(1A) receptors, was more potent in the septum (pEC(50) approximately 6.5) than in the dentate gyrus of the hippocampus (pEC(50) approximately 5) suggesting potential differences in coupling efficiency or G protein expression. Though clozapine (30 and 100 microM) did not enhance [(35)S]GTPgammaS labelling in any structure, S16924 (10 micro M) modestly increased [(35)S]GTPgammaS labelling in the dentate gyrus. On the other hand, both these antipsychotic agents attenuated 5-HT (10 microM)-stimulated [(35)S]GTPgammaS binding in the dentate gyrus and septum. In conclusion, clozapine, S16924 and ziprasidone act as partial agonists for G

  10. Activation of sodium channels by α-scorpion toxin, BmK NT1, produced neurotoxicity in cerebellar granule cells: an association with intracellular Ca2+ overloading.

    Science.gov (United States)

    He, Yuwei; Zou, Xiaohan; Li, Xichun; Chen, Juan; Jin, Liang; Zhang, Fan; Yu, Boyang; Cao, Zhengyu

    2017-02-01

    Voltage-gated sodium channels (VGSCs) are responsible for the action potential generation in excitable cells including neurons and involved in many physiological and pathological processes. Scorpion toxins are invaluable tools to explore the structure and function of ion channels. BmK NT1, a scorpion toxin from Buthus martensii Karsch, stimulates sodium influx in cerebellar granule cells (CGCs). In this study, we characterized the mode of action of BmK NT1 on the VGSCs and explored the cellular response in CGC cultures. BmK NT1 delayed the fast inactivation of VGSCs, increased the Na + currents, and shifted the steady-state activation and inactivation to more hyperpolarized membrane potential, which was similar to the mode of action of α-scorpion toxins. BmK NT1 stimulated neuron death (EC 50  = 0.68 µM) and produced massive intracellular Ca 2+ overloading (EC 50  = 0.98 µM). TTX abrogated these responses, suggesting that both responses were subsequent to the activation of VGSCs. The Ca 2+ response of BmK NT1 was primary through extracellular Ca 2+ influx since reducing the extracellular Ca 2+ concentration suppressed the Ca 2+ response. Further pharmacological evaluation demonstrated that BmK NT1-induced Ca 2+ influx and neurotoxicity were partially blocked either by MK-801, an NMDA receptor blocker, or by KB-R7943, an inhibitor of Na + /Ca 2+ exchangers. Nifedipine, an L-type Ca 2+ channel inhibitor, slightly suppressed both Ca 2+ response and neurotoxicity. A combination of these three inhibitors abrogated both responses. Considered together, these data ambiguously demonstrated that activation of VGSCs by an α-scorpion toxin was sufficient to produce neurotoxicity which was associated with intracellular Ca 2+ overloading through both NMDA receptor- and Na + /Ca 2+ exchanger-mediated Ca 2+ influx.

  11. Noradrenaline represses PPAR (peroxisome-proliferator-activated receptor) gamma2 gene expression in brown adipocytes: intracellular signalling and effects on PPARgamma2 and PPARgamma1 protein levels

    DEFF Research Database (Denmark)

    Lindgren, Eva M; Nielsen, Ronni; Petrovic, Natasa

    2004-01-01

    phases, with the highest mRNA levels being found at the time of transition between the phases. PPARgamma2 mRNA levels were downregulated by noradrenaline treatment (EC50, 0.1 microM) in both proliferative and differentiating cells, with a lagtime of 1 h and lasting up to 4 h, after which expression...... was thus to investigate the influence of noradrenaline on PPARgamma gene expression in brown adipocytes. In primary cultures of brown adipocytes, PPARgamma2 mRNA levels were 20-fold higher than PPARgamma1 mRNA levels. PPARgamma expression occurred during both the proliferation and the differentiation...... gradually recovered. The down-regulation was beta-adrenoceptor-induced and intracellularly mediated via cAMP and protein kinase A; the signalling pathway did not involve phosphoinositide 3-kinase, Src, p38 mitogen-activated protein kinase or extracellular-signal-regulated kinases 1 and 2. Treatment...

  12. Antibacterial, Antioxidant, and Anticholinesterase Activities of Plant Seed Extracts from Brazilian Semiarid Region

    Directory of Open Access Journals (Sweden)

    Davi Felipe Farias

    2013-01-01

    Full Text Available The antimicrobial, antioxidant, and anticholinesterase activities of ethanolic seed extracts of twenty-one plant species from Brazilian semiarid region were investigated. The extracts were tested for antimicrobial activity against six bacteria strains and three yeasts. Six extracts presented activity against the Gram (− organism Salmonella choleraesuis and the Gram (+ organisms Staphylococcus aureus and Bacillus subtilis. The MIC values ranged from 4.96 to 37.32 mg/mL. The Triplaris gardneriana extract presented activity against the three species, with MIC values 18.8, 13.76, and 11.15 mg/mL, respectively. Five extracts presented antioxidant activity, with EC50 values ranging from 69.73 μg/mL (T. gardneriana to 487.51 μg/mL (Licania rigida. For the anticholinesterase activity, eleven extracts were capable of inhibiting the enzyme activity. From those, T. gardneriana, Parkia platycephala and Connarus detersus presented the best activities, with inhibition values of 76.7, 71.5, and 91.9%, respectively. The extracts that presented antimicrobial activity were tested for hemolytic assay against human A, B, and O blood types and rabbit blood. From those, only the Myracrodruon urundeuva extract presented activity (about 20% of hemolysis at the lowest tested concentration, 1.9 µg/mL. Infrared spectroscopy of six representative extracts attested the presence of tannins, polyphenols, and flavonoids, which was confirmed by a qualitative phytochemical assay.

  13. Antibacterial, antioxidant, and anticholinesterase activities of plant seed extracts from Brazilian semiarid region.

    Science.gov (United States)

    Farias, Davi Felipe; Souza, Terezinha Maria; Viana, Martônio Ponte; Soares, Bruno Marques; Cunha, Arcelina Pacheco; Vasconcelos, Ilka Maria; Ricardo, Nágila Maria Pontes Silva; Ferreira, Paulo Michel Pinheiro; Melo, Vânia Maria Maciel; Carvalho, Ana Fontenele Urano

    2013-01-01

    The antimicrobial, antioxidant, and anticholinesterase activities of ethanolic seed extracts of twenty-one plant species from Brazilian semiarid region were investigated. The extracts were tested for antimicrobial activity against six bacteria strains and three yeasts. Six extracts presented activity against the Gram (-) organism Salmonella choleraesuis and the Gram (+) organisms Staphylococcus aureus and Bacillus subtilis. The MIC values ranged from 4.96 to 37.32 mg/mL. The Triplaris gardneriana extract presented activity against the three species, with MIC values 18.8, 13.76, and 11.15 mg/mL, respectively. Five extracts presented antioxidant activity, with EC50 values ranging from 69.73 μ g/mL (T. gardneriana) to 487.51 μ g/mL (Licania rigida). For the anticholinesterase activity, eleven extracts were capable of inhibiting the enzyme activity. From those, T. gardneriana, Parkia platycephala and Connarus detersus presented the best activities, with inhibition values of 76.7, 71.5, and 91.9%, respectively. The extracts that presented antimicrobial activity were tested for hemolytic assay against human A, B, and O blood types and rabbit blood. From those, only the Myracrodruon urundeuva extract presented activity (about 20% of hemolysis at the lowest tested concentration, 1.9 µg/mL). Infrared spectroscopy of six representative extracts attested the presence of tannins, polyphenols, and flavonoids, which was confirmed by a qualitative phytochemical assay.

  14. Blandford's argument: The strongest continuous gravitational wave signal

    International Nuclear Information System (INIS)

    Knispel, Benjamin; Allen, Bruce

    2008-01-01

    For a uniform population of neutron stars whose spin-down is dominated by the emission of gravitational radiation, an old argument of Blandford states that the expected gravitational-wave amplitude of the nearest source is independent of the deformation and rotation frequency of the objects. Recent work has improved and extended this argument to set upper limits on the expected amplitude from neutron stars that also emit electromagnetic radiation. We restate these arguments in a more general framework, and simulate the evolution of such a population of stars in the gravitational potential of our galaxy. The simulations allow us to test the assumptions of Blandford's argument on a realistic model of our galaxy. We show that the two key assumptions of the argument (two dimensionality of the spatial distribution and a steady-state frequency distribution) are in general not fulfilled. The effective scaling dimension D of the spatial distribution of neutron stars is significantly larger than two, and for frequencies detectable by terrestrial instruments the frequency distribution is not in a steady state unless the ellipticity is unrealistically large. Thus, in the cases of most interest, the maximum expected gravitational-wave amplitude does have a strong dependence on the deformation and rotation frequency of the population. The results strengthen the previous upper limits on the expected gravitational-wave amplitude from neutron stars by a factor of 6 for realistic values of ellipticity.

  15. The Strength of the Strongest Ties in Collaborative Problem Solving

    DEFF Research Database (Denmark)

    de Montjoye, Yves-Alexandre; Stopczynski, Arkadiusz; Shmueli, Erez

    2014-01-01

    an effect on performance. Both networks of strong ties explain more of the variance than other factors, such as measured or self-evaluated technical competencies, or the personalities of the team members. In fact, the inclusion of the network of strong ties renders these factors non...

  16. Antioxidant activity, the content of total phenols and flavonoids in the ethanol extracts of Mentha longifolia (L. Hudson dried by the use of different techniques

    Directory of Open Access Journals (Sweden)

    Stanisavljević Dragana M.

    2012-01-01

    Full Text Available In this study, we have examined the yield of extracted substances obtained by means of extraction using 70 % ethanol (v/v, the content of total phenols and flavonoids, as well as the antioxidant activity of the extracts obtained from the samples of the herbs dried by means of different techniques. Wild mint Mentha longifolia (L. Hudson was dried naturally in a laboratory oven at a temperature of 45 °C and in an absorptive low temperature condensation oven at 35°C. The highest yield of extracts was obtained from the naturally dried herbs and the lowest from the herbs dried in the low temperature condensation drying oven. The content of total phenols and flavonoids was determined by spectrophotometric methods with an FC reagent and by the complexation reaction with aluminium-chloride, respectively. The extract of the naturally dried herbs had the highest overall content of phenols (113.8±2.0 mg of gallic acid/g of the dry extract and flavonoids (106.7±0.3 mg of rutin/g of the dry extract. The highest antioxidant activity determined by the FRAP and DPPH assay was determined in the extracts obtained from naturally dried herbs (2.76±0.15 mmol Fe2+/mg of the dry extract and EC50=0.022±0.001 mg/ml, while the lowest was obtained from the extracts of herbs dried in the laboratory oven (1.13±0.11 mmol Fe2+/mg of the dry extract and EC50=0.033±0.001 mg/ml. The HPLC-DAD analysis result show that the greatest content of phenolic compounds show extract obtained from naturally dried plant material. The dominant phenolic component in the all extracts is Kaempferol 3-O-glucoside. The content of all phenolic compound strongly depend on the drying conditions.

  17. Biological activities of undescribed North American lichen species.

    Science.gov (United States)

    Yeash, Erik A; Letwin, Lyndon; Malek, Lada; Suntres, Zacharias; Knudsen, Kerry; Christopher, Lew P

    2017-11-01

    Lichens provide a large array of compounds with the potential for pharmaceutical development. In the present study, extracts from three previously undescribed North American lichen species were examined for antioxidant, antibacterial and anticancer activities. The results from this study demonstrated the following: (i) Acarospora socialis ethanol extract exhibited significant DPPH antioxidant scavenging activities, which were concentration dependent; (ii) acetone and ethyl acetate extracts of Xanthoparmelia mexicana inhibited Gram-positive bacteria but had no effect on Gram-negative bacteria; X. mexicana acetone extract yielded a minimum inhibitory concentration (MIC) of 20.9 µg mL -1 against Staphylococcus aureus, and 41.9 µg mL -1 against Enterococcus faecalis; (iii) acetone extract of Lobothallia alphoplaca inhibited growth of cultured breast cancer MCF-7 cells with an effective concentration (EC 50 ) of 87 µg mL -1 ; the MCF-7 cell cycle appears arrested in the G2 phase, whereas the DNA synthesis cell cycle (S) may be inhibited. New lichen species that possess strong biological activities have been identified. These lichens comprise secondary metabolites that possess antioxidant, antibacterial and anticancer properties. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  18. Fractionation of the more active extracts of Geranium molle L.: a relationship between their phenolic profile and biological activity.

    Science.gov (United States)

    Graça, V C; Dias, Maria Inês; Barros, Lillian; Calhelha, Ricardo C; Santos, P F; Ferreira, Isabel C F R

    2018-04-25

    Geranium molle L., commonly known as Dove's-foot Crane's-bill or Dovesfoot Geranium, is an herbaceous plant belonging to the Geraniaceae family. Contrary to many other Geranium species, the bioactivity and the phytochemical composition of G. molle seem not to have attracted attention until a recent study from our group regarding the bioactivity of several aqueous and organic extracts of the plant. In particular, we assessed the cytotoxic activity of these extracts against several human tumor cell lines (breast, lung, cervical and hepatocellular carcinomas) and a non-tumor porcine liver primary cell line, inspired by an ethnopharmacological report describing the traditional use of this medicinal plant in some regions of Northeast Portugal for the treatment of cancer. Following this preliminary evaluation, the most active extracts (acetone and methanol) were fractionated by column chromatography and the resulting fractions were evaluated for their antioxidant activity and cytotoxicity against the same cell lines. The bio-guided fractionation of the extracts resulted in several fractions exhibiting improved bioactivity in comparison with the corresponding crude extracts. The fractions obtained from the acetone extract consistently displayed the lowest EC50 and GI50 values and presented the highest content of total phenolic compounds. The phytochemical composition of the most bioactive fractions of the acetone and methanol extracts was also determined and about thirty compounds, mainly flavonoids and phenolic acids, could be identified for the first time in G. molle.

  19. Additive and synergistic antiandrogenic activities of mixtures of azol fungicides and vinclozolin.

    Science.gov (United States)

    Christen, Verena; Crettaz, Pierre; Fent, Karl

    2014-09-15

    Many pesticides including pyrethroids and azole fungicides are suspected to have an endocrine disrupting property. At present, the joint activity of compound mixtures is only marginally known. Here we tested the hypothesis that the antiandrogenic activity of mixtures of azole fungicides can be predicted by the concentration addition (CA) model. The antiandrogenic activity was assessed in MDA-kb2 cells. Following assessing single compounds activities mixtures of azole fungicides and vinclozolin were investigated. Interactions were analyzed by direct comparison between experimental and estimated dose-response curves assuming CA, followed by an analysis by the isobole method and the toxic unit approach. The antiandrogenic activity of pyrethroids deltamethrin, cypermethrin, fenvalerate and permethrin was weak, while the azole fungicides tebuconazole, propiconazole, epoxiconazole, econazole and vinclozolin exhibited strong antiandrogenic activity. Ten binary and one ternary mixture combinations of five antiandrogenic fungicides were assessed at equi-effective concentrations of EC25 and EC50. Isoboles indicated that about 50% of the binary mixtures were additive and 50% synergistic. Synergism was even more frequently indicated by the toxic unit approach. Our data lead to the conclusion that interactions in mixtures follow the CA model. However, a surprisingly high percentage of synergistic interactions occurred. Therefore, the mixture activity of antiandrogenic azole fungicides is at least additive. Mixtures should also be considered for additive antiandrogenic activity in hazard and risk assessment. Our evaluation provides an appropriate "proof of concept", but whether it equally translates to in vivo effects should further be investigated. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Chemical composition, insecticidal, and antifungal activities of fruit essential oils of three colombian Zanthoxylum species Composición química, actividades insecticida y antifúngica de aceites esenciales de frutos de tres especies Zanthoxylum de Colombia

    Directory of Open Access Journals (Sweden)

    Juliet A Prieto

    2011-03-01

    Full Text Available This study determined the chemical composition of essential oils isolated from Zanthoxylum monophyllum (Lam. P. Wilson, Z. rhoifolium Lam., and Z. fagara (L. Sarg. fruits by steam distillation, as well as testing antifungal and insecticidal activities of essential oils as potential pesticides. Gas chromatography-mass spectrometry (GC/MS analysis identified 57 compounds. The main constituents in Z. rhoifolium oil were β-Myrcene (59.03%, β-phellandrene (21.47%, and germacrene D (9.28% , the major constituents of Z. monophyllum oil were sabinene (25.71%, 1,8-cineole (9.19%, and cis-4-thujanol (9.19%, whereas fruit oil of Z. fagara mainly contained germacrene D-4-ol (21.1%, elemol (8.35%, and α-cadinol (8.22%. Zanthoxylum fagara showed the highest activity on Colletotrichum acutatum Simmonds (EC50 153.9 μL L-1 air, and Z. monophyllum was the most active against Fusarium oxysporum Schlechtend: Fr. f. sp. lycopersici (EC50 140.1 μL L-1 air. Zanthoxylum monophyllum essential oil showed significant fumigant activity against Sitophilus oryzae (L.. This study demonstrated that Zanthoxylum essential oils exhibit important fungicidal activity on F. oxysporum and C. acutatum, which could become an alternative to synthetic fungicides to control plant fungal diseases, and Z. monophyllum oil is a potential fumigant against S. oryzae.En este estudio se determinó la composición química de los aceites esenciales de frutos de Zanthoxylum monophyllum (Lam. P. Wilson, Z. rhoifolium Lam. y Z. fagara (L. Sarg. obtenidos mediante destilación por arrastre con vapor y se evaluó la actividad antifúngica e insecticida de los aceites esenciales para estimar su uso como posibles plaguicidas. El análisis por cromatografía de gases-espectrometría de masas (CG/EM permitió la identificación de 57 compuestos. β-Mirceno (59,03%, β-felandreno (21,47% y germacreno D (9,28% fueron los componentes principales del aceite de Z. rhoifolium; los principales componentes

  1. Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin.

    Science.gov (United States)

    Deck, Lorraine M; Hunsaker, Lucy A; Vander Jagt, Thomas A; Whalen, Lisa J; Royer, Robert E; Vander Jagt, David L

    2018-01-01

    Inflammation and oxidative stress are common in many chronic diseases. Targeting signaling pathways that contribute to these conditions may have therapeutic potential. The transcription factor Nrf2 is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. Nrf2 is widespread in the CNS and is recognized as an important regulator of brain inflammation. The natural product curcumin exhibits numerous biological activities including ability to induce the expression of Nrf2-dependent phase II and anti-oxidant enzymes. Curcumin has been examined in a number of clinical studies with limited success, mainly owing to limited bioavailability and rapid metabolism. Enone analogues of curcumin were examined with an Nrf2 reporter assay to identify Nrf2 activators. Analogues were separated into groups with a 7-carbon dienone spacer, as found in curcumin; a 5-carbon enone spacer with and without a ring; and a 3-carbon enone spacer. Activators of Nrf2 were found in all three groups, many of which were more active than curcumin. Dose-response studies demonstrated that a range of substituents on the aromatic rings of these enones influenced not only the sensitivity to activation, reflected in EC 50 values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2 by these analogues. Copyright © 2017. Published by Elsevier Masson SAS.

  2. Purification, structural characterization, and myotropic activity of a peptide related to des-Arg(9)-bradykinin from an elasmobranch fish, the little skate, Leucoraja erinacea.

    Science.gov (United States)

    Anderson, W Gary; Leprince, Jérôme; Conlon, J Michael

    2008-08-01

    A bradykinin (BK)-related peptide was isolated from heat-denaturated plasma from an elasmobranch fish, the little skate, Leucoraja erinacea after incubation with porcine pancreatic kallikrein. The primary structure of the peptide (H-Gly-Ile-Thr-Ser-Trp-Leu-Pro-Phe-OH; skate BK) shows limited structural similarity to the mammalian B1 receptor agonist, des-Arg(9)-BK. The myotropic activities of synthetic skate BK, and the analog skate [Arg(9)]BK, were examined in isolated skate vascular and intestinal smooth muscle preparations. Skate BK produced a concentration-dependent constriction of the mesenteric artery (EC(50)=4.37x10(-8)M; maximum response=103.4+/-10.23% of the response to 60mM KCl) but the response to skate [Arg(9)]BK was appreciably weaker (response to 10(-6)M=73.0+/-23.4% of the response to 60mM KCl). Neither the first branchial gill arch nor the ventral aorta responded to either purified peptide. Skate BK also produced a concentration-dependent constriction of intestinal smooth muscle preparations (EC(50)=2.74x10(-7)M; maximum response 31.0+/-12.2% of the response to 10(-5)M acetylcholine). Skate [Arg(9)]BK was without effect on the intestinal preparation. The data provide evidence for the existence of the kallikrein-kinin system in a phylogenetically ancient vertebrate group and the greater potency of skate BK compared with the analog skate [Arg(9)]BK suggests that the receptor mediating vascular responses resembles the mammalian B1 receptor more closely than the B2 receptor.

  3. Toxicity Assessment of Atrazine and Related Triazine Compounds in the Microtox Assay, and Computational Modeling for Their Structure-Activity Relationship

    Directory of Open Access Journals (Sweden)

    Jerzy Leszczynski

    2000-10-01

    Full Text Available The triazines are a group of chemically similar herbicides including atrazine, cyanazine, and propazine, primarily used to control broadleaf weeds. About 64 to 80 million lbs of atrazine alone are used each year in the United States, making it one of the two most widely used pesticides in the country. All triazines are somewhat persistent in water and mobile in soil. They are among the most frequently detected pesticides in groundwater. They are considered as possible human carcinogens (Group C based on an increase in mammary gland tumors in female laboratory animals. In this research, we performed the Microtox Assay to investigate the acute toxicity of a significant number of triazines including atrazine, atraton, ametryne, bladex, prometryne, and propazine, and some of their degradation products including atrazine desethyl, atrazine deisopropyl, and didealkyled triazine. Tests were carried out as described by Azur Environmental [1]. The procedure measured the relative acute toxicity of triazines, producing data for the calculation of triazine concentrations effecting 50% reduction in bioluminescence (EC50s. Quantitative structure-activity relationships (QSAR were examined based on the molecular properties obtained from quantum mechanical predictions performed for each compound. Toxicity tests yielded EC50 values of 39.87, 273.20, 226.80, 36.96, 81.86, 82.68, 12.74, 11.80, and 78.50 mg/L for atrazine, propazine, prometryne, atraton, atrazine desethyl, atrazine deisopropyl, didealkylated triazine, ametryne, and bladex, respectively; indicating that ametryne was the most toxic chemical while propazine was the least toxic. QSAR evaluation resulted in a coefficient of determination (r2 of 0.86, indicating a good value of toxicity prediction based on the chemical structures/properties of tested triazines.

  4. Monoubiquitination Inhibits the Actin Bundling Activity of Fascin.

    Science.gov (United States)

    Lin, Shengchen; Lu, Shuang; Mulaj, Mentor; Fang, Bin; Keeley, Tyler; Wan, Lixin; Hao, Jihui; Muschol, Martin; Sun, Jianwei; Yang, Shengyu

    2016-12-30

    Fascin is an actin bundling protein that cross-links individual actin filaments into straight, compact, and stiff bundles, which are crucial for the formation of filopodia, stereocillia, and other finger-like membrane protrusions. The dysregulation of fascin has been implicated in cancer metastasis, hearing loss, and blindness. Here we identified monoubiquitination as a novel mechanism that regulates fascin bundling activity and dynamics. The monoubiquitination sites were identified to be Lys 247 and Lys 250 , two residues located in a positive charge patch at the actin binding site 2 of fascin. Using a chemical ubiquitination method, we synthesized chemically monoubiquitinated fascin and determined the effects of monoubiquitination on fascin bundling activity and dynamics. Our data demonstrated that monoubiquitination decreased the fascin bundling EC 50 , delayed the initiation of bundle assembly, and accelerated the disassembly of existing bundles. By analyzing the electrostatic properties on the solvent-accessible surface of fascin, we proposed that monoubiquitination introduced steric hindrance to interfere with the interaction between actin filaments and the positively charged patch at actin binding site 2. We also identified Smurf1 as a E3 ligase regulating the monoubiquitination of fascin. Our findings revealed a previously unidentified regulatory mechanism for fascin, which will have important implications for the understanding of actin bundle regulation under physiological and pathological conditions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Monoubiquitination Inhibits the Actin Bundling Activity of Fascin*

    Science.gov (United States)

    Lin, Shengchen; Lu, Shuang; Mulaj, Mentor; Fang, Bin; Keeley, Tyler; Wan, Lixin; Hao, Jihui; Muschol, Martin; Sun, Jianwei; Yang, Shengyu

    2016-01-01

    Fascin is an actin bundling protein that cross-links individual actin filaments into straight, compact, and stiff bundles, which are crucial for the formation of filopodia, stereocillia, and other finger-like membrane protrusions. The dysregulation of fascin has been implicated in cancer metastasis, hearing loss, and blindness. Here we identified monoubiquitination as a novel mechanism that regulates fascin bundling activity and dynamics. The monoubiquitination sites were identified to be Lys247 and Lys250, two residues located in a positive charge patch at the actin binding site 2 of fascin. Using a chemical ubiquitination method, we synthesized chemically monoubiquitinated fascin and determined the effects of monoubiquitination on fascin bundling activity and dynamics. Our data demonstrated that monoubiquitination decreased the fascin bundling EC50, delayed the initiation of bundle assembly, and accelerated the disassembly of existing bundles. By analyzing the electrostatic properties on the solvent-accessible surface of fascin, we proposed that monoubiquitination introduced steric hindrance to interfere with the interaction between actin filaments and the positively charged patch at actin binding site 2. We also identified Smurf1 as a E3 ligase regulating the monoubiquitination of fascin. Our findings revealed a previously unidentified regulatory mechanism for fascin, which will have important implications for the understanding of actin bundle regulation under physiological and pathological conditions. PMID:27879315

  6. Antifouling Activity of Lipidic Metabolites Derived from Padina tetrastromatica.

    Science.gov (United States)

    Suresh, Murugan; Iyapparaj, Palanisamy; Anantharaman, Perumal

    2016-07-01

    An attempt has been made to identify the potential seaweed for antifouling property due to the growing need for environmentally safe antifouling systems. The antibacterial, antimicroalgal, and antimussel foot adherence potentials of methanol, dichloromethane, and hexane extracts of the chosen seaweeds such as Padina tetrastromatica, Caulerpa taxifolia, and Amphiroa fragilissima have been compared against copper sulfate. Among the extracts, the maximum antibacterial activities were exhibited by the methanol extract of P. tetrastromatica. The minimum inhibitory concentration (MIC) of the methanolic extract of P. tetrastromatica was found to be 10 and 1 μg/ml against test biofilm bacteria and diatoms, respectively. The antimussel foot adherence assay indicated that the extract had inhibited the foot adherence of the green mussels Perna viridis with the effective concentration (EC50) of 25.51 ± 0.03 μg/ml, and lethal concentration for 50 % mortality (LC50) was recorded at 280.22 ± 0.12 μg/ml. Based on the prolific results, the crude methanolic extract of P. tetrastromatica was subjected to purification using silica gel column and thin-layer chromatography (TLC). Then, the active compounds of the bioassay-guided fraction (F13) were identified using gas chromatography coupled with mass spectroscopy (GC-MS), and it was observed that fatty acids were the major components, which may be responsible for the antifouling properties.

  7. Antifungal activity of some essential oils against toxigenic Aspergillus species.

    Science.gov (United States)

    Alizadeh, Alireza; Zamani, Elham; Sharaifi, Rohollah; Javan-Nikkhah, Mohammad; Nazari, Somayeh

    2010-01-01

    Increasing attentions have been paid on the application of essential oils and plant extracts for control of postharvest pathogens due to their natural origin and less appearance of resistance in fungi pathogens. Some Aspergillus species are toxigenic and responsible for many cases of food and feed contamination. Some Toxins that produce with some Aspergillus species are known to be potent hepatocarcinogens in animals and humans. The present work evaluated the parameters of antifungal activity of the essential oils of Zataria multiflora, Thymus migricus, Satureja hortensis, Foeniculum vulgare, Carum capticum and thiabendazol fungicide on survival and growth of different species of Aspergillus. Aerial part and seeds of plant species were collected then dried and its essential oils isolated by means of hydrodistillation. Antifungal activity was evaluated in vitro by poisonous medium technique with PDA medium at six concentrations. Results showed that all essential oils could inhibit the growth of Aspergillus species. The essential oil with the best effect and lowest EC50 and MIC (Minimum Inhibitory Concentration) was Z. multiflora (223 microl/l and 650 microl/l, respectively). The chemical composition of the Z. multiflora essential oil was analyzed by GC-MS.

  8. Free radical scavenging actions of three Trifolium species in the protection of blood plasma antioxidant capacity in vitro.

    Science.gov (United States)

    Kolodziejczyk-Czepas, Joanna; Nowak, Pawel; Moniuszko-Szajwaj, Barbara; Kowalska, Iwona; Stochmal, Anna

    2015-01-01

    Three clover [Trifolium L. (Leguminosae)] species were selected on the basis of data from traditional medicine, phytochemical profiles, and agricultural significance. The in vitro evaluations of free radical scavenging properties, ferric reducing abilities, and antioxidant effects of extracts from T. pratense L. (crude extract and phenolic fraction), T. pallidum L., and T. scabrum L. (phenolic fractions) were performed. Activities of the Trifolium extracts were determined at their final concentrations of 1.5-50 µg/ml. Free radical scavenging properties of methanol extract solutions were estimated by the reduction of DPPH(•) and ABTS(•) radicals. Measurements of the total antioxidant capacity (TAC) were carried out to assess the antioxidant activities of the extracts in human blood plasma under conditions of oxidative stress, induced by 200 μM peroxynitrite. The phenolic fraction of T. pratense displayed the strongest ABTS(•) and DPPH(•) radical scavenging effects (EC50 value of 21.69 and 12.27 µg/ml, respectively). The EC50 value for T. pallidum extract attained 29.77 and 30.06 µg/ml. The two remaining extracts were less potent scavengers (EC50 value higher than 50 µg/ml). Similar differences were obtained during evaluation of the ferric reducing abilities. Analysis of antioxidant properties of the extracts in blood plasma did not provide such evident differences in their actions, however, it indicated that the T. pratense phenolic fraction displayed the strongest effect. The examined Trifolium extracts partly protected blood plasma and enhanced its non-enzymatic antioxidant defense against harmful action of peroxynitrite in vitro.

  9. Reversible anti-settlement activity against Amphibalanus (= Balanus ) amphitrite, Bugula neritina , and Hydroides elegans by a nontoxic pharmaceutical compound, mizolastine

    KAUST Repository

    Zhou, Xiaojian; Xu, Ying; Jin, Cuili; Qian, Pei-Yuan

    2009-01-01

    Mizolastine, an antihistamine pharmaceutical, was found to significantly inhibit larval settlement of the barnacle Amphibalanus (=Balanus) amphitrite, the bryozoan Bugula neritina, and the polychaete Hydroides elegans with EC50 values of 4.2, 11

  10. In vitro antioxidant and antiproliferative activities of methanolic plant part extracts of Theobroma cacao.

    Science.gov (United States)

    Baharum, Zainal; Akim, Abdah Md; Taufiq-Yap, Yun Hin; Hamid, Roslida Abdul; Kasran, Rosmin

    2014-11-10

    The aims of this study were to determine the antioxidant and antiproliferative activity of the following Theobroma cacao plant part methanolic extracts: leaf, bark, husk, fermented and unfermented shell, pith, root, and cherelle. Antioxidant activity was determined using 2,2-diphenyl-2-picrylhydrazyl (DPPH), thiobarbituric acid-reactive substances (TBARS), and Folin-Ciocalteu assays; the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT) assay was used to determine antiproliferative activity. The root extract had the highest antioxidant activity; its median effective dose (EC50) was 358.3±7.0 µg/mL and total phenolic content was 22.0±1.1 g GAE/100 g extract as compared to the other methanolic plant part extracts. Only the cherelle extract demonstrated 10.4%±1.1% inhibition activity in the lipid peroxidation assay. The MTT assay revealed that the leaf extract had the highest antiproliferative activity against MCF-7 cells [median inhibitory concentration (IC50)=41.4±3.3 µg/mL]. Given the overall high IC50 for the normal liver cell line WRL-68, this study indicates that T. cacao methanolic extracts have a cytotoxic effect in cancer cells, but not in normal cells. Planned future investigations will involve the purification, identification, determination of the mechanisms of action, and molecular assay of T. cacao plant extracts.

  11. In Vitro Antioxidant and Antiproliferative Activities of Methanolic Plant Part Extracts of Theobroma cacao

    Directory of Open Access Journals (Sweden)

    Zainal Baharum

    2014-11-01

    Full Text Available The aims of this study were to determine the antioxidant and antiproliferative activity of the following Theobroma cacao plant part methanolic extracts: leaf, bark, husk, fermented and unfermented shell, pith, root, and cherelle. Antioxidant activity was determined using 2,2-diphenyl-2-picrylhydrazyl (DPPH, thiobarbituric acid-reactive substances (TBARS, and Folin-Ciocalteu assays; the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT assay was used to determine antiproliferative activity. The root extract had the highest antioxidant activity; its median effective dose (EC50 was 358.3 ± 7.0 µg/mL and total phenolic content was 22.0 ± 1.1 g GAE/100 g extract as compared to the other methanolic plant part extracts. Only the cherelle extract demonstrated 10.4% ± 1.1% inhibition activity in the lipid peroxidation assay. The MTT assay revealed that the leaf extract had the highest antiproliferative activity against MCF-7 cells [median inhibitory concentration (IC50 = 41.4 ± 3.3 µg/mL]. Given the overall high IC50 for the normal liver cell line WRL-68, this study indicates that T. cacao methanolic extracts have a cytotoxic effect in cancer cells, but not in normal cells. Planned future investigations will involve the purification, identification, determination of the mechanisms of action, and molecular assay of T. cacao plant extracts.

  12. In vitro Antioxidant Activities of Sodium Zinc and Sodium Iron Chlorophyllins from Pine Needles

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    Ruzhen Zhan

    2014-01-01

    Full Text Available Chlorophyll was extracted from pine needles, and then sodium zinc chlorophyllin (SZC and sodium iron chlorophyllin (SIC were synthesised by saponification, purification and substitution reaction, using sodium copper chlorophyllin (SCC as a control. Their crystalline structures were verified by atomic absorbance spectroscopy, UV-VIS spectroscopy and HPLC. Moreover, their antioxidant activities were evaluated and compared with that of ascorbic acid through four biochemical assays: DPPH (2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, reducing power, inhibition of β-carotene bleaching and O2– scavenging activity. SZC had better antioxidant properties at a lower dosage than SIC and SCC in all assays. In the β-carotene bleaching assay, EC50 of SZC, SIC and SCC was 0.04, 0.38 and 0.90 mg/mL, respectively, much lower than that of ascorbic acid (4.0 mg/mL. SZC showed a better result (p<0.05 than ascorbic acid in the O2 – scavenging activity assay. The results obtained from reducing power determination were also excellent: the absorbance values were all about 1.0 at 0.5 mg/mL, about half of that of ascorbic acid. In the investigation of DPPH radical scavenging activity, all chlorophyllins had lower activities than ascorbic acid. These results demonstrated the potential bioactivities of chlorophyll derivatives and supported their possible role in human health protection and disease prevention.

  13. Antibacterial and antioxidant activities and acute toxicity of Bumelia sartorum Mart., Sapotaceae, a Brazilian medicinal plant

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    Halliny S. Ruela

    2011-03-01

    Full Text Available In order to validate the Bumelia sartorum Mart., Sapotaceae, traditional use for infection diseases, this study evaluates the antibacterial activity of the stem bark fractions against methicillin-sensitive (MSSA and methicillin-resistant (MRSA Staphylococcus aureus strains by using the agar dilution method and reported as MIC (minimal inhibitory concentration. In addition, the DPPH scavenging activity of these fractions was measured and the chemical composition and acute toxicity of the active fraction were also determined. The ethyl acetate (EtOAc extract was chemically analyzed by LC/MS, direct ionization APCI/MS, ¹H NMR and 13C-NMR. All fractions, except butanol extract, presented high antioxidant activity, especially the methanol and the EtOAc extracts, which showed EC50 values (5.67 and 5.30 µg/mL, respectively considerably lower than the Gingko-standard EGb 761® (38.58 µg/mL. The antibacterial activity against S. aureus strains was observed in EtOAc (MIC 256-512 µg/mL, which showed a very low toxicity. The chemical study of this fraction revealed the abundant presence of polyphenolic compounds. The antibacterial and antioxidant activities reported in this paper for EtOAc extract from B. sartorum and the low toxicity of this fraction opens the possibility that it could be helpful for the developing of new antibacterial agents for treating S. aureus infections.

  14. Evaluation of Analgesic Activity of Papaver libanoticum Extract in Mice: Involvement of Opioids Receptors

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    Mohamad Ali Hijazi

    2017-01-01

    Full Text Available Papaver libanoticum is an endemic plant to Lebanese region (family Papaveraceae that has not been investigated before. The present study aimed to explore the analgesic activity of dried ethanolic extract of Papaver libanoticum (PLE using tail flick, hot plate, and acetic acid induced writhing models in mice. The involvement of opioid receptors in the analgesic mechanism was investigated using naloxone antagonism. Results demonstrated that PLE exhibited a potent dose dependent analgesic activity in all tested models for analgesia. The analgesic effect involved activation of opioid receptors in the central nervous system, where both spinal and supraspinal components might be involved. The time course for analgesia revealed maximum activity after three hours in both tail flick and hot plate methods, which was prolonged to 24 hours. Metabolites of PLE could be responsible for activation of opioid receptors. The EC50 of PLE was 79 and 50 mg/kg in tail flick and hot plate tests, respectively. The total coverage of analgesia by PLE was double that of morphine in both tests. In conclusion, PLE proved to have opioid agonistic activity with a novel feature of slow and prolonged effect. The present study could add a potential tool in the armaments of opioid drugs as a natural potent analgesic and for treatment of opioid withdrawal syndrome.

  15. Endocrine Activity of AVB, 2MR, BHA, and Their Mixtures.

    Science.gov (United States)

    Klopcic, Ivana; Dolenc, Marija Sollner

    2017-03-01

    Personal care products are used increasingly, resulting in growing concern concerning their potential disruption of normal hormonal functions. Recent results on the bioaccumulation of cosmetic ingredients in wildlife and humans point to the need for an in-depth analysis for endocrine activity, in particular with respect to their influence on the androgen (AR), glucocorticoid (GR), and thyroid hormone receptors (TRs). Furthermore, humans are commonly exposed simultaneously to complex mixtures of endocrine active compounds. We have therefore examined 3 frequently used cosmetic ingredients: 2-methylresorcinol (2MR), butylated hydroxyanisole (BHA) and avobenzone (AVB), for (anti)-androgen-, (anti)-glucocorticoid-, and (anti)-thyroid hormone-like activities. Their binary and ternary mixtures at EC50 or IC50 concentrations have also been examined for anti-androgen-, glucocorticoid-, and thyroid hormone-like activities. In the MDA-kb2 reporter cell line, compounds possessed anti-androgen-, glucocorticoid-, and anti-glucocorticoid-like activities (except AVB). A new cell line, GH3.TRE-Luc, was used to evaluate anti-thyroid and thyroid hormone-like activities. The combinations 2MR + BHA and 2MR + BHA + AVB have glucocorticoid-like activity: only 2MR + AVB has anti-androgen-like activity. On the other hand, binary and ternary mixtures of compounds showed no thyroid hormone-like activity. Thus, in addition to identifying new endocrine disrupting compounds, it is also necessary to determine the effects of their mixtures in order to assess fully their risk to human health. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. In Vitro inhibitory activity of Alpinia katsumadai extracts against influenza virus infection and hemagglutination

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    Park Su-Jin

    2010-11-01

    Full Text Available Abstract Background Alpinia katsumadai (AK extracts and fractions were tested for in vitro antiviral activities against influenza virus type A, specially human A/PR/8/34 (H1N1 and avian A/Chicken/Korea/MS96/96 (H9N2, by means of time-of-addition experiments; pre-treatment, simultaneous treatment, and post treatment. Results In pre-treatment assay, the AK extracts and AK fractions did not show significant antiviral activity. During the simultaneous treatment assay, one AK extract and five AK fractions designated as AK-1 to AK-3, AK-5, AK-10, and AK-11 showed complete inhibition of virus infectivity against A/PR/8/34 (H1N1 and A/Chicken/Korea/MS96/96 (H9N2. The 50% effective inhibitory concentrations (EC50 of these one AK extracts and five AK fractions with exception of the AK-9 were from 0.8 ± 1.4 to 16.4 ± 4.5 μg/mL against A/PR/8/34 (H1N1. The two AK extracts and three AK fractions had EC50 values ranging from μg/mL against A/Chicken/Korea/MS96/96 (H9N2. By the hemagglutination inhibition (HI assay, the two AK extracts and five AK fractions completely inhibited viral adsorption onto chicken RBCs at less than 100 μg/mL against both A/PR/8/34 (H1N1 and A/Chicken/Korea/MS96/96 (H9N2. Interestingly, only AK-3 was found with inhibition for both viral attachment and viral replication after showing extended antiviral activity during the post treatment assay and quantitative real-time PCR. Conclusions These results suggest that AK extracts and fractions had strong anti-influenza virus activity that can inhibit viral attachment and/or viral replication, and may be used as viral prophylaxis.

  17. Chemical Composition and Biological Activities of Mono- and Heterofloral Bee Pollen of Different Geographical Origins

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    Jucilene Silva Araújo

    2017-04-01

    Full Text Available Recent research shows variations in pollen chemical constituents and, consequently, in their therapeutic properties. Mono and multifloral bee pollen extracts were investigated for antioxidant and enzyme inhibitory activity properties, phenolic compounds and fatty acid composition. Generally, Eucalyptus spp. and multifloral extracts exhibited potent inhibitory activity against α-amylase, acetylcholinesterase, tyrosinase, lipoxygenase, lipase and hyaluronidase. On the other hand, Miconia spp. demonstrated higher antihemolytic activity. Cocos nucifera and Miconia spp. extracts exhibited important antioxidant properties in the different assays (ABTS, DPPH, β-carotene/linoleic acid and reducing power. Moreover, these extracts had greater amounts of total phenols and flavonoids in comparison to others. The increase in antioxidant activity (decrease in EC50 values was accompanied by an increase in the amount of total phenols in the extracts. The pollen extracts contained linoleic acid and α-linolenic acid as major fatty acids, followed by palmitic acid, and oleic acid. In this study, differences were observed in both chemical constituents and biological activities of the samples related to the geographical and botanical origin of bee pollen.

  18. Preparation and Characterizations of Chitosan/Citral Nanoemulsions and their Antimicrobial Activity

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    Gehan I. Kh. Marei

    2018-03-01

    Full Text Available Background and Objective: The antimicrobial activity of essential oils has been long recognized, however, they easily evaporate and/or decompose during preparation, owing to direct exposure to heat, pressure and light. The current study deals with the formulation and characterization of bio-based oil in water nanoemulsions and their antimicrobial activity against plant pathogens.Material and Methods: Citral oil and low molecular weight chitosan were used for preparation of nanoemulsions in the presence of sodium tripolyphosphate. Nanoemulsions were prepared by adding dropwise citral at different ratios into an aqueous solution containing chitosan, sodium tripolyphosphate and surfactant with continuous stirring and then ultrasonication. The success of formulation was confirmed by dynamic light scattering and scanning electron microscopy techniques. Physical stability and viscosity were investigated in details. The antimicrobial activity was evaluated against Erwinia carotovora, Aspergillus niger and Rhizopus stolonifer. Results and Conclusion: The nanoemulsions had a polydispersity index ranged from 0.508 to 0.614 and particle size from 27 to 1283 nm. The highest antimicrobial activity was observed with F1 formulation (EC50 = 23, 278 and 221 mg L-1, against Erwinia carotovora, Aspergillus niger and Rhizopus stolonifer, respectively. Based on the antimicrobial activity, the prepared chitosan/citral nanoemulsions can be a cost-effective way to protect crops from microbial pathogens. Because such formulations contain bioactive products, the development of resistant pathogens can be delayed.Conflict of Interest: The authors declare no conflict of interest. 

  19. Dasatinib inhibits both osteoclast activation and prostate cancer PC-3-cell-induced osteoclast formation.

    Science.gov (United States)

    Araujo, John C; Poblenz, Ann; Corn, Paul; Parikh, Nila U; Starbuck, Michael W; Thompson, Jerry T; Lee, Francis; Logothetis, Christopher J; Darnay, Bryant G

    2009-11-01

    Therapies to target prostate cancer bone metastases have only limited effects. New treatments are focused on the interaction between cancer cells, bone marrow cells and the bone matrix. Osteoclasts play an important role in the development of bone tumors caused by prostate cancer. Since Src kinase has been shown to be necessary for osteoclast function, we hypothesized that dasatinib, a Src family kinase inhibitor, would reduce osteoclast activity and prostate cancer (PC-3) cell-induced osteoclast formation. Dasatinib inhibited RANKL-induced osteoclast differentiation of bone marrow-derived monocytes with an EC(50) of 7.5 nM. PC-3 cells, a human prostate cancer cell line, were able to differentiate RAW 264.7 cells, a murine monocytic cell line, into osteoclasts, and dasatinib inhibited this differentiation. In addition, conditioned medium from PC-3 cell cultures was able to differentiate RAW 264.7 cells into osteoclasts and this too, was inhibited by dasatinib. Even the lowest concentration of dasatinib, 1.25 nmol, inhibited osteoclast differentiation by 29%. Moreover, dasatinib inhibited osteoclast activity by 58% as measured by collagen 1 release. We performed in vitro experiments utilizing the Src family kinase inhibitor dasatinib to target osteoclast activation as a means of inhibiting prostate cancer bone metastases. Dasatinib inhibits osteoclast differentiation of mouse primary bone marrow-derived monocytes and PC-3 cell-induced osteoclast differentiation. Dasatinib also inhibits osteoclast degradation activity. Inhibiting osteoclast differentiation and activity may be an effective targeted therapy in patients with prostate cancer bone metastases.

  20. Assessment of Antioxidant and Cytotoxicity Activities of Saponin and Crude Extracts of Chlorophytum borivilianum

    Science.gov (United States)

    Abd Aziz, Maheran; Stanslas, Johnson; Abdul Kadir, Mihdzar

    2013-01-01

    The present paper focused on antioxidant and cytotoxicity assessment of crude and total saponin fraction of Chlorophytum borivilianum as an important medicinal plant. In this study, three different antioxidant activities (2,2-diphenyl-1-picrylhydrazyl radical scavenging (DPPH), ferrous ion chelating (FIC), and β-carotene bleaching (BCB) activity) of crude extract and total saponin fraction of C. borivilianum tubers were performed. Crude extract was found to possess higher free radical scavenging activity (ascorbic acid equivalents 2578 ± 111 mg AA/100 g) and bleaching activity (IC50 = 0.7 mg mL−1), while total saponin fraction displayed higher ferrous ion chelating (EC50 = 1 mg mL−1). Cytotoxicity evaluation of crude extract and total saponin fraction against MCF-7, PC3, and HCT-116 cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) cell viability assay indicated a higher cytotoxicity activity of the crude extract than the total saponin fraction on all cell lines, being most effective and selective on MCF-7 human breast cancer cell line. PMID:24223502

  1. Effect of norfloxacin and moxifloxacin on melanin synthesis and antioxidant enzymes activity in normal human melanocytes.

    Science.gov (United States)

    Beberok, Artur; Wrześniok, Dorota; Otręba, Michał; Miliński, Maciej; Rok, Jakub; Buszman, Ewa

    2015-03-01

    Fluoroquinolone antibiotics provide broad-spectrum coverage for a number of infectious diseases, including respiratory as well as urinary tract infections. One of the important adverse effects of these drugs is phototoxicity which introduces a serious limitation to their use. To gain insight the molecular mechanisms underlying the fluoroquinolones-induced phototoxic side effects, the impact of two fluoroquinolone derivatives with different phototoxic potential, norfloxacin and moxifloxacin, on melanogenesis and antioxidant enzymes activity in normal human melanocytes HEMa-LP was determined. Both drugs induced concentration-dependent loss in melanocytes viability. The value of EC50 for these drugs was found to be 0.5 mM. Norfloxacin and moxifloxacin suppressed melanin biosynthesis; antibiotics were shown to inhibit cellular tyrosinase activity and to reduce melanin content in melanocytes. When comparing the both analyzed fluoroquinolones, it was observed that norfloxacin possesses greater inhibitory effect on tyrosinase activity in melanocytes than moxifloxacin. The extent of oxidative stress in cells was assessed by measuring the activity of antioxidant enzymes: SOD, CAT, and GPx. It was observed that norfloxacin caused higher depletion of antioxidant status in melanocytes when compared with moxifloxacin. The obtained results give a new insight into the mechanisms of fluoroquinolones toxicity directed to pigmented tissues. Moreover, the presented differences in modulation of biochemical processes in melanocytes may be an explanation for various phototoxic activities of the analyzed fluoroquinolone derivatives in vivo.

  2. Effect of carbaryl (carbamate insecticide) on acetylcholinesterase activity of two strains of Daphnia magna (Crustacea, Cladocera).

    Science.gov (United States)

    Toumi, Hela; Bejaoui, Mustapha; Touaylia, Samir; Burga Perez, Karen F; Ferard, Jean François

    2016-11-01

    The present study was designed to investigate the effect of carbaryl (carbamate insecticide) on the acetylcholinesterase activity in two strains (same clone A) of the crustacean cladoceran Daphnia magna. Four carbaryl concentrations (0.4, 0.9, 1.8 and 3.7 µg L(-1)) were compared against control AChE activity. Our results showed that after 48 h of carbaryl exposure, all treatments induced a significant decrease of AChE activities whatever the two considered strains. However, different responses were registered in terms of lowest observed effect concentrations (LOEC: 0.4 µg L(-1) for strain 1 and 0.9 µg L(-1) for strains 2) revealing differences in sensitivity among the two tested strains of D. magna. These results suggest that after carbaryl exposure, the AChE activity responses can be also used as a biomarker of susceptibility. Moreover, our results show that strain1 is less sensitive than strain 2 in terms of IC50-48 h of AChE activity. Comparing the EC50-48 h of standard ecotoxicity test and IC50-48 h of AChE inhibition, there is the same order of sensitivity with both strains.

  3. Mosquitocidal Activity and Mode of Action of the Isoxazoline Fluralaner.

    Science.gov (United States)

    Jiang, Shiyao; Tsikolia, Maia; Bernier, Ulrich R; Bloomquist, Jeffrey R

    2017-02-06

    Mosquitoes, such as Aedes aegypti and Anopheles gambiae , are important vectors of human diseases. Fluralaner, a recently introduced parasiticide, was evaluated as a mosquitocide in this study. On Ae. aegypti and An. gambiae fourth-instar larvae, fluralaner had 24-h LC 50 (lethal concentration for 50% mortality) values of 1.8 ppb and 0.4 ppb, respectively. Following topical application to adult Ae. aegypti , fluralaner toxicity reached a plateau in about 3 days, with 1- and 3-day LD 50 (lethal dose for 50% mortality) values of 1.3 ng/mg and 0.26 ng/mg, suggesting a slowly developing toxicity. Fipronil outperformed fluralaner by up to 100-fold in adult topical, glass contact, and feeding assays on Ae. aegypti . These data show that fluralaner does not have exceptional toxicity to mosquitoes in typical exposure paradigms. In electrophysiological recordings on Drosophila melanogaster larval central nervous system, the effectiveness of fluralaner for restoring nerve firing after gamma-aminobutyric acid (GABA) treatment, a measure of GABA antagonism, was similar in susceptible Oregon-R and cyclodiene-resistant rdl -1675 strains, with EC 50 (half maximal effective concentration) values of 0.34 µM and 0.29 µM. Although this finding suggests low cross resistance in the presence of rdl , the moderate potency, low contact activity, and slow action of fluralaner argue against its use as an adult mosquitocide for vector control.

  4. Mosquitocidal Activity and Mode of Action of the Isoxazoline Fluralaner

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    Shiyao Jiang

    2017-02-01

    Full Text Available Mosquitoes, such as Aedes aegypti and Anopheles gambiae, are important vectors of human diseases. Fluralaner, a recently introduced parasiticide, was evaluated as a mosquitocide in this study. On Ae. aegypti and An. gambiae fourth-instar larvae, fluralaner had 24-h LC50 (lethal concentration for 50% mortality values of 1.8 ppb and 0.4 ppb, respectively. Following topical application to adult Ae. aegypti, fluralaner toxicity reached a plateau in about 3 days, with 1- and 3-day LD50 (lethal dose for 50% mortality values of 1.3 ng/mg and 0.26 ng/mg, suggesting a slowly developing toxicity. Fipronil outperformed fluralaner by up to 100-fold in adult topical, glass contact, and feeding assays on Ae. aegypti. These data show that fluralaner does not have exceptional toxicity to mosquitoes in typical exposure paradigms. In electrophysiological recordings on Drosophila melanogaster larval central nervous system, the effectiveness of fluralaner for restoring nerve firing after gamma-aminobutyric acid (GABA treatment, a measure of GABA antagonism, was similar in susceptible Oregon-R and cyclodiene-resistant rdl-1675 strains, with EC50 (half maximal effective concentration values of 0.34 µM and 0.29 µM. Although this finding suggests low cross resistance in the presence of rdl, the moderate potency, low contact activity, and slow action of fluralaner argue against its use as an adult mosquitocide for vector control.

  5. Terbinafine is a novel and selective activator of the two-pore domain potassium channel TASK3.

    Science.gov (United States)

    Wright, Paul D; Veale, Emma L; McCoull, David; Tickle, David C; Large, Jonathan M; Ococks, Emma; Gothard, Gemma; Kettleborough, Catherine; Mathie, Alistair; Jerman, Jeffrey

    2017-11-04

    Two-pore domain potassium channels (K2Ps) are characterized by their four transmembrane domain and two-pore topology. They carry background (or leak) potassium current in a variety of cell types. Despite a number of important roles there is currently a lack of pharmacological tools with which to further probe K2P function. We have developed a cell-based thallium flux assay, using baculovirus delivered TASK3 (TWIK-related acid-sensitive K + channel 3, KCNK9, K2P9.1) with the aim of identifying novel, selective TASK3 activators. After screening a library of 1000 compounds, including drug-like and FDA approved molecules, we identified Terbinafine as an activator of TASK3. In a thallium flux assay a pEC50 of 6.2 ( ±0.12) was observed. When Terbinafine was screened against TASK2, TREK2, THIK1, TWIK1 and TRESK no activation was observed in thallium flux assays. Several analogues of Terbinafine were also purchased and structure activity relationships examined. To confirm Terbinafine's activation of TASK3 whole cell patch clamp electrophysiology was carried out and clear potentiation observed in both the wild type channel and the pathophysiological, Birk-Barel syndrome associated, G236R TASK3 mutant. No activity at TASK1 was observed in electrophysiology studies. In conclusion, we have identified the first selective activator of the two-pore domain potassium channel TASK3. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Antifungal Activity and Biochemical Response of Cuminic Acid against Phytophthora capsici Leonian.

    Science.gov (United States)

    Wang, Yong; Sun, Yang; Zhang, Ying; Zhang, Xing; Feng, Juntao

    2016-06-11

    Phytophthora blight of pepper caused by Phytophthora capsici Leonian is a destructive disease throughout the world. Cuminic acid, extracted from the seed of Cuminum cyminum L., belongs to the benzoic acid chemical class. In this study, the sensitivity and biochemical response of P. capsici to cuminic acid was determined. The mean EC50 (50% effective concentration) values for cuminic acid in inhibiting mycelial growth and zoospore germination of the 54 studied P. capsici isolates were 14.54 ± 5.23 μg/mL and 6.97 ± 2.82 μg/mL, respectively. After treatment with cuminic acid, mycelial morphology, sporangium formation and mycelial respiration were significantly influenced; cell membrane permeability and DNA content increased markedly, but pyruvic acid content, adenosine triphosphate (ATP) content, and ATPase activity decreased compared with the untreated control. In pot experiments, cuminic acid exhibited both protective and curative activity. Importantly, POD and PAL activity of the pepper leaves increased after being treated with cuminic acid. These indicated that cuminic acid not only showed antifungal activity, but also could improve the defense capacity of the plants. All the results suggested that cuminic acid exhibits the potential to be developed as a new phytochemical fungicide, and this information increases our understanding of the mechanism of action of cuminic acid against Phytophthora capsici.

  7. Comparative evaluation of two Trichoderma harzianum strains for major secondary metabolite production and antifungal activity.

    Science.gov (United States)

    Ahluwalia, Vivek; Kumar, Jitendra; Rana, Virendra S; Sati, Om P; Walia, S

    2015-01-01

    This investigation was undertaken to identify the major secondary metabolite, produced by two Trichoderma harzianum strains (T-4 and T-5) with their antifungal activity against phytopathogenic fungi using poison food technique. The ethyl acetate extract was subjected to column chromatography using n-hexane, ethyl acetate and methanol gradually. Chromatographic separation of ethyl acetate extract of T. harzianum (T-4) resulted in the isolation and identification of palmitic acid (1), 1,8-dihydroxy-3-methylanthraquinone (2), 6-pentyl-2H-pyran-2-one (3), 2(5H)-furanone (4), stigmasterol (5) and β-sitosterol (6), while T. harzianum (T-5) gave palmitic acid (1), 1-hydroxy-3-methylanthraquinone (7), δ-decanolactone (8), 6-pentyl-2H-pyran-2-one (3), ergosterol (9), harzianopyridone (10) and 6-methyl-1,3,8-trihydroxyanthraquinone (11) as major metabolites. Among compounds screened for antifungal activity, compound 10 was found to be most active (EC50 35.9-50.2 μg mL(-1)). In conclusion, the present investigation provided significant information about antifungal activity and compounds isolated from two different strains of T. harzianum obtained from two different Himalayan locations.

  8. Izalpinin from fruits of Alpinia oxyphylla with antagonistic activity against the rat bladder contractility.

    Science.gov (United States)

    Yuan, Yuan; Tan, Yin-Feng; Xu, Peng; Li, Hailong; Li, Yong-Hui; Chen, Wen-Ya; Zhang, Jun-Qing; Chen, Feng; Huang, Guo-Jun

    2014-01-01

    Alpinia oxyphylla (Zingiberaceae), an herbaceous perennial plant, its capsular fruit is commonly used in traditional Chinese medicine for the treatment of different urinary incontinence symptoms including frequency, urgency and nocturia. These symptoms are similar to the overactive bladder syndrome. In our lab, we found that the 95% ethanol extract of the capsular fruits exhibited significant anti-muscarinic activity. Some constituents in capsular fruits including flavonoids (e.g., izalpinin and tectochrysin), diarylheptanoids (e.g., yakuchinone A and yakuchinone B) and sesquiterpenes (e.g., nootkatone), are regarded as representative chemicals with putative pharmacological activities. This study aimed to evaluate the in vitro antagonistic actions of izalpinin on carbachol-induced contraction of the rat detrusor muscle. In vitro inhibition of rat detrusor contractile response to carbachol was used to study the functional activity of izalpinin. The isolated detrusor strips of rats were mounted in organ baths containing oxygenated Krebs' solution. The cumulative consecutive concentration-response curves to carbachol-evoked contractions in strips of rat bladder were obtained. Carbachol induced concentration-dependent contractions of isolated rat bladder detrusor strips. The vehicle DMSO had no impact on the contraction response. The contraction effects were concentration-dependently antagonized by izalpinin, with a mean EC50 value of 0.35 µM. The corresponding cumulative agonist concentration-response curves shifted right-ward. Izalpinin exhibits inhibitory role of muscarinic receptor-related detrusor contractile activity, and it may be a promising lead compound to treat overactive bladder.

  9. Antioxidant and Antiplasmodial Activities of Bergenin and 11-O-Galloylbergenin Isolated from Mallotus philippensis

    Science.gov (United States)

    Khan, Hamayun; Amin, Hazrat; Ullah, Asad; Saba, Sumbal; Rafique, Jamal; Khan, Khalid; Ahmad, Nasir; Badshah, Syed Lal

    2016-01-01

    Two important biologically active compounds were isolated from Mallotus philippensis. The isolated compounds were characterized using spectroanalytical techniques and found to be bergenin (1) and 11-O-galloylbergenin (2). The in vitro antioxidant and antiplasmodial activities of the isolated compounds were determined. For the antioxidant potential, three standard analytical protocols, namely, DPPH radical scavenging activity (RSA), reducing power assay (RPA), and total antioxidant capacity (TAC) assay, were adopted. The results showed that compound 2 was found to be more potent antioxidant as compared to 1. Fascinatingly, compound 2 displayed better EC50 results as compared to α-tocopherol while being comparable with ascorbic acid. The antiplasmodial assay data showed that both the compound exhibited good activity against chloroquine sensitive strain of Plasmodium falciparum (D10) and IC50 values were found to be less than 8 μM. The in silico molecular docking analyses were also performed for the determination of binding affinity of the isolated compounds using P. falciparum proteins PfLDH and Pfg27. The results showed that compound 2 has high docking score and binding affinity to both protein receptors as compared to compound 1. The demonstrated biological potentials declared that compound 2 could be the better natural antioxidant and antiplasmodial candidate. PMID:26998192

  10. Antioxidant and Antiplasmodial Activities of Bergenin and 11-O-Galloylbergenin Isolated from Mallotus philippensis

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    Hamayun Khan

    2016-01-01

    Full Text Available Two important biologically active compounds were isolated from Mallotus philippensis. The isolated compounds were characterized using spectroanalytical techniques and found to be bergenin (1 and 11-O-galloylbergenin (2. The in vitro antioxidant and antiplasmodial activities of the isolated compounds were determined. For the antioxidant potential, three standard analytical protocols, namely, DPPH radical scavenging activity (RSA, reducing power assay (RPA, and total antioxidant capacity (TAC assay, were adopted. The results showed that compound 2 was found to be more potent antioxidant as compared to 1. Fascinatingly, compound 2 displayed better EC50 results as compared to α-tocopherol while being comparable with ascorbic acid. The antiplasmodial assay data showed that both the compound exhibited good activity against chloroquine sensitive strain of Plasmodium falciparum (D10 and IC50 values were found to be less than 8 μM. The in silico molecular docking analyses were also performed for the determination of binding affinity of the isolated compounds using P. falciparum proteins PfLDH and Pfg27. The results showed that compound 2 has high docking score and binding affinity to both protein receptors as compared to compound 1. The demonstrated biological potentials declared that compound 2 could be the better natural antioxidant and antiplasmodial candidate.

  11. Physical Activity for Health and Longevity

    OpenAIRE

    Khoo, Selina; Müller, Andre Matthias

    2013-01-01

    International audience; The aging process is commonly associated with declines in health, cognitive function and well-being. However, lifestyle factors like diet, alcohol consumption, smoking and physical activity were repeatedly highlighted as predictors of a healthy aging process. However, recent research has shown that physical activity is the strongest predictor of health in older adults. Recent studies have confirmed the strong effect of physical activity on cardiovascular, metabolic, mu...

  12. Synthesis, Leishmanicidal and Cytotoxic Activity of Triclosan-Chalcone, Triclosan-Chromone and Triclosan-Coumarin Hybrids

    Directory of Open Access Journals (Sweden)

    Elver Otero

    2014-08-01

    Full Text Available Twelve hybrids derived from triclosan were obtained via Williamson etherification of O-triclosan alkyl bromide plus chalcone and O-coumarin or O-chromone alkyl bromide plus triclosan, respectively. Structures of the products were elucidated by spectroscopic analysis. The synthesized compounds were evaluated for antileishmanial activity against L. (V panamensis amastigotes. Cytotoxic activity was also evaluated against mammalian U-937 cells. Compounds 7–9 and 17, were active against Leishmania parasites (EC50 = 9.4; 10.2; 13.5 and 27.5 µg/mL, respectively and showed no toxicity toward mammalian cells (>200 µg/mL. They are potential candidates for antileishmanial drug development. Compounds 25–27, were active and cytotoxic. Further studies using other cell types are needed in order to discriminate whether the toxicity shown by these compounds is against tumor or non-tumor cells. The results indicate that compounds containing small alkyl chains show better selectivity indices. Moreover, Michael acceptor moieties may modify both the leishmanicidal activity and cytotoxicity. Further studies are required to evaluate if the in vitro activity against Leishmania panamensis demonstrated here is also observed in vivo.

  13. Study on antioxidant and antimicrobial activities of turmeric clear liquid soap for wound treatment of HIV patients

    Directory of Open Access Journals (Sweden)

    Pechnoi Singchangchai

    2005-08-01

    Full Text Available Ethanol extract of turmeric [Curcuma longa Linn. (Zingiberaceae] was investigated for its in vitro antioxidant activity using 1,1-diphenyl-2-picrylhydrazyl (DPPH radical scavenging assay and activities against six microorganisms (Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, Staphyloccoccus aureus, Candida albicans and Cryptococcus neoformans. Clear liquid soaps containing 0.5% w/v turmeric extract were formulated. The only one preparation with acceptable appearance, foam and viscosity was selected for antimicrobial activity and stability studies. It was found that turmeric extract had 50% radical scavenging ability (EC50 at concentration of 11.26 μg/ml against DPPH. Turmeric extract was showed no activity against Escherichia coli and Pseudomonas aeruginosa. The minimum inhibitory concentration of turmeric extract against Bacillus subtilis, Staphyloccocus aureus, Cryptococcus neoformans and Candida albicans were 16, 128, 128 and 256 μg/ml, respectively. The selected preparation was physically and chemically stable and the antimicrobial activity did not change (p<0.05 under the heating-cooling stability test. However, curcumin content and the antimicrobial activities against S. aureus and C. neoformans decreased significantly (p<0.05 under the accelerated test conditions (temperature 45oC, 75% RH for 4 months and after storage at room temperature for 12 months. The results of a clinical trial with HIV patients found that this liquid soap decreased itching symptom (100% and infectious wound and abscess became dryness scabs (78.6% within 2 weeks.

  14. Environmental phthalate monoesters activate pregnane X receptor-mediated transcription

    International Nuclear Information System (INIS)

    Hurst, Christopher H.; Waxman, David J.

    2004-01-01

    Phthalate esters, widely used as plasticizers in the manufacture of products made of polyvinyl chloride, induce reproductive and developmental toxicities in rodents. The mechanism that underlies these effects of phthalate exposure, including the potential role of members of the nuclear receptor superfamily, is not known. The present study investigates the effects of phthalates on the pregnane X receptor (PXR), which mediates the induction of enzymes involved in steroid metabolism and xenobiotic detoxification. The ability of phthalate monoesters to activate PXR-mediated transcription was assayed in a HepG2 cell reporter assay following transfection with mouse PXR (mPXR), human PXR (hPXR), or the hPXR allelic variants V140M, D163G, and A370T. Mono-2-ethylhexyl phthalate (MEHP) increased the transcriptional activity of both mPXR and hPXR (5- and 15-fold, respectively) with EC 50 values of 7-8 μM. mPXR and hPXR were also activated by monobenzyl phthalate (MBzP, up to 5- to 6-fold) but were unresponsive to monomethyl phthalate and mono-n-butyl phthalate (M(n)BP) at the highest concentrations tested (300 μM). hPXR-V140M and hPXR-A370T exhibited patterns of phthalate responses similar to the wild-type receptor. By contrast, hPXR-D163G was unresponsive to all phthalate monoesters tested. Further studies revealed that hPXR-D163G did respond to rifampicin, but required approximately 40-fold higher concentrations than wild-type receptor, suggesting that the ligand-binding domain D163G variant has impaired ligand-binding activity. The responsiveness of PXR to activation by phthalate monoesters demonstrated here suggests that these ubiquitous environmental chemicals may, in part, exhibit their endocrine disruptor activities by altering PXR-regulated steroid hormone metabolism with potential adverse health effects in exposed individuals

  15. Flavonoids as Vasorelaxant Agents: Synthesis, Biological Evaluation and Quantitative Structure Activities Relationship (QSAR Studies

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    Yongzhou Hu

    2011-09-01

    Full Text Available A series of 2-(2-diethylamino-ethoxychalcone and 6-prenyl(or its isomers-flavanones 10a,b and 11a–g were synthesized and evaluated for their vasorelaxant activities against rat aorta rings pretreated with 1 μM phenylephrine (PE. Several compounds showed potent vasorelaxant activities. Compound 10a (EC50 = 7.6 μM, Emax = 93.1%, the most potent one, would be a promising structural template for development of novel and more efficient vasodilators. Further, 2D-QSAR analysis of compounds 10a,b and 11c-e as well as thirty previously synthesized flavonoids 1-3 and 12-38 using Enhanced Replacement Method-Multiple Linear Regression (ERM-MLR was further performed based on an optimal set of molecular descriptors (H5m, SIC2, DISPe, Mor03u and L3m, leading to a reliable model with good predictive ability (Rtrain2 = 0.839, Qloo2 = 0.733 and Rtest2 = 0.804. The results provide good insights into the structure- activity relationships of the target compounds.

  16. Correlation between phosphatidylinositol labeling and contraction in rabbit aorta: effect of alpha-1 adrenergic activation

    International Nuclear Information System (INIS)

    Villalobos-Molina, R.; Uc, M.; Hong, E.; Garcia-Sainz, J.A.

    1982-01-01

    Activation of rabbit aortic strips with alpha adrenergic agonists increased the labeling (with [ 32 P]Pi) of phosphatidylinositol (PI) and phosphatidic acid and contracted the vascular preparations in dose-related fashion. Epinephrine, norepinephrine and methoxamine produced maximal effects, whereas clonidine behaved as partial agonist and B-HT 933 (2-amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazole-[5,4-d] azepin dihydrochloride) was almost without activity in the two experimental models used. Phenylephrine was a full agonist in producing contraction, but failed to elicit the maximal increase in PI labeling. The EC50 values to produce contraction of aortic strips were lower for all agonists than those required to increase the incorporation of radioactive phosphate into PI, but there was a good correlation between the two sets of data. The increased PI labeling and contraction of aortic strips induced by epinephrine were antagonized by prazosin and yohimbine in dose-related fashion, but the first alpha blocker was about three orders of magnitude more potent than the second in antagonizing the two effects. The present results indicate that both stimulation of PI labeling and contraction are mediated through activation of alpha-1 adrenoceptors in rabbit aorta

  17. Response of soil microbial activities and microbial community structure to vanadium stress.

    Science.gov (United States)

    Xiao, Xi-Yuan; Wang, Ming-Wei; Zhu, Hui-Wen; Guo, Zhao-Hui; Han, Xiao-Qing; Zeng, Peng

    2017-08-01

    High levels of vanadium (V) have long-term, hazardous impacts on soil ecosystems and biological processes. In the present study, the effects of V on soil enzymatic activities, basal respiration (BR), microbial biomass carbon (MBC), and the microbial community structure were investigated through 12-week greenhouse incubation experiments. The results showed that V content affected soil dehydrogenase activity (DHA), BR, and MBC, while urease activity (UA) was less sensitive to V stress. The average median effective concentration (EC 50 ) thresholds of V were predicted using a log-logistic dose-response model, and they were 362mgV/kg soil for BR and 417mgV/kg soil for DHA. BR and DHA were more sensitive to V addition and could be used as biological indicators for soil V pollution. According to a polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) analysis, the structural diversity of the microbial community decreased for soil V contents ranged between 254 and 1104mg/kg after 1 week of incubation. As the incubation time increased, the diversity of the soil microbial community structure increased for V contents ranged between 354 and 1104mg/kg, indicating that some new V-tolerant bacterial species might have replicated under these conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Ovicidal activity of succinic acid isolated from sisal waste (Agave sisalana against gastrointestinal nematodes of goats

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    Nathália Silva de Souza Santos

    Full Text Available ABSTRACT: This study was conducted to evaluate the in vitro anthelmintic activity of the succinic acid (SA isolated from sisal waste against gastrointestinal nematodes of goats, using the egg hatching and larvae motility assays. In addition, potential cytotoxicity of SA on Vero cell cultures was investigated by means of MTT (3-4,5-dimethylthiazol-2-yl, 2,5diphenyltetrazolium bromide test. The SA induced a significant inhibition of egg hatching (P<0.05 at all concentrations tested (60 to 250µg mL-1, and the concentrations to inhibit 50% (EC50 and 90% (EC90 values (mean ± standard deviation were 90.3±2.8 and 130.6±3.5µg mL-1, respectively. The SA has not shown larvicidal activity. The SA was less toxic to the Vero cells, with the mean percentage of cell viability equal to 85±6.2% at the concentration of 130µg mL-1. The results suggested that SA has potential anthelmintic effect; although, more research is needed to confirm its activity in vivo.

  19. A proton-activated, outwardly rectifying chloride channel in human umbilical vein endothelial cells

    International Nuclear Information System (INIS)

    Ma Zhiyong; Zhang Wei; Chen Liang; Wang Rong; Kan Xiaohong; Sun Guizhen; Liu Chunxi; Li Li; Zhang Yun

    2008-01-01

    Extracellular acidic pH-activated chloride channel I Cl,acid , has been characterized in HEK 293 cells and mammalian cardiac myocytes. This study was designed to characterize I Cl,acid in human umbilical vein endothelial cells(HUVECs). The activation and deactivation of the current rapidly and repeatedly follows the change of the extracellular solution at pH 4.3, with the threshold pH 5.3. In addition, at very positive potentials, the current displays a time-dependent facilitation. pH-response relationship for I Cl,acid revealed that EC 50 is pH 4.764 with a threshold pH value of pH 5.3 and nH of 14.545. The current can be blocked by the Cl - channel inhibitor DIDS (100 μM). In summary, for the first time we report the presence of proton-activated, outwardly rectifying chloride channel in HUVECs. Because an acidic environment can develop in local myocardium under pathological conditions such as myocardial ischemia, I Cl,acid would play a role in regulation of EC function under these pathological conditions

  20. Kaempferol ameliorates symptoms of metabolic syndrome by regulating activities of liver X receptor-β.

    Science.gov (United States)

    Hoang, Minh-Hien; Jia, Yaoyao; Mok, Boram; Jun, Hee-jin; Hwang, Kwang-Yeon; Lee, Sung-Joon

    2015-08-01

    Kaempferol is a dietary flavonol previously shown to regulate cellular lipid and glucose metabolism. However, its molecular mechanisms of action and target proteins have remained elusive, probably due to the involvement of multiple proteins. This study investigated the molecular targets of kaempferol. Ligand binding of kaempferol to liver X receptors (LXRs) was quantified by time-resolved fluorescence resonance energy transfer and surface plasmon resonance analyses. Kaempferol directly binds to and induces the transactivation of LXRs, with stronger specificity for the β-subtype (EC50 = 0.33 μM). The oral administration of kaempferol in apolipoprotein-E-deficient mice (150 mg/day/kg body weight) significantly reduced plasma glucose and increased high-density lipoprotein cholesterol levels and insulin sensitivity compared with the vehicle-fed control. Kaempferol also reduced plasma triglyceride concentrations and did not cause liver steatosis, a common side effect of potent LXR activation. In immunoblotting analysis, kaempferol reduced the nuclear accumulation of sterol regulatory element-binding protein-1 (SREBP-1). Our results show that the suppression of SREBP-1 activity and the selectivity for LXR-β over LXR-α by kaempferol contribute to the reductions of plasma and hepatic triglyceride concentrations in mice fed kaempferol. They also suggest that kaempferol activates LXR-β and suppresses SREBP-1 to enhance symptoms in metabolic syndrome. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Antiviral activity of some Tunisian medicinal plants against Herpes simplex virus type 1.

    Science.gov (United States)

    Sassi, A Ben; Harzallah-Skhiri, F; Bourgougnon, N; Aouni, M

    2008-01-10

    Fifteen species of Tunisian traditional medicinal plants, belonging to 10 families, were selected for this study. They were Inula viscosa (L.) Ait and Reichardia tingitana (L.) Roth ssp. discolor (Pom.) Batt. (Asteraceae), Mesembryanthemum cristallinum L. and M. nodiflorum L. (Aizoaceae), Arthrocnemum indicum (Willd.) Moq., Atriplex inflata Muell., A. parvifolia Lowe var. ifiniensis (Caball) Maire, and Salicornia fruticosa L. (Chenopodiaceae), Cistus monspeliensis L. (Cistaceae), Juniperus phoenicea L. (Cupressaceae), Erica multiflora L. (Ericaceae), Frankenia pulverulenta L. (Frankeniaceae), Hypericum crispum L. (Hypericaceae), Plantago coronopus L. ssp. eu-coronopus Pilger var. vulgaris G.G. (Plantaginaceae) and Zygophyllum album L. (Zygophyllaceae). Fifty extracts prepared from those plants were screened in order to assay their antiviral activity against Herpes simplex virus type 1 (HSV-1), using neutral red incorporation. Extracts from eight plants among these 15 showed some degree of antiviral activity, while the methanolic extract of E. multiflora was highly active with EC(50) of 132.6 microg mL(-1). These results corroborate that medicinal plants from Tunisia can be a rich source of potential antiviral compounds.

  2. Cytotoxic, Virucidal, and Antiviral Activity of South American Plant and Algae Extracts

    Directory of Open Access Journals (Sweden)

    Paula Faral-Tello

    2012-01-01

    Full Text Available Herpes simplex virus type 1 (HSV-1 infection has a prevalence of 70% in the human population. Treatment is based on acyclovir, valacyclovir, and foscarnet, three drugs that share the same mechanism of action and of which resistant strains have been isolated from patients. In this aspect, innovative drug therapies are required. Natural products offer unlimited opportunities for the discovery of antiviral compounds. In this study, 28 extracts corresponding to 24 plant species and 4 alga species were assayed in vitro to detect antiviral activity against HSV-1. Six of the methanolic extracts inactivated viral particles by direct interaction and 14 presented antiviral activity when incubated with cells already infected. Most interesting antiviral activity values obtained are those of Limonium brasiliense, Psidium guajava, and Phyllanthus niruri, which inhibit HSV-1 replication in vitro with 50% effective concentration (EC50 values of 185, 118, and 60 μg/mL, respectively. For these extracts toxicity values were calculated and therefore selectivity indexes (SI obtained. Further characterization of the bioactive components of antiviral plants will pave the way for the discovery of new compounds against HSV-1.

  3. Effect of gamma irradiation on the extraction yield, antioxidant, and antityrosinase activities of pistachio green hull extract

    Science.gov (United States)

    Abolhasani, Ali; Barzegar, Mohsen; Sahari, Mohammad Ali

    2018-03-01

    In this study, the antioxidant activity and tyrosinase inhibitory of non-irradiated and irradiated pistachio green hull (PGH) extracts were investigated. After irradiation of PGH by different doses of gamma ray (0, 10, 20, 30 and 40 kGy), their phenolic compounds were extracted by water. Antioxidant activities of extracts were examined by DPPH• and FRAP methods. The results showed that irradiation not only do not have negative effects on antioxidant activity but also it can increase the amount of total phenolic compounds of water extract in comparison with non-irradiated sample. Water extract of irradiated PGH at the dose of 30 kGy, showed the highest antioxidant activity in the DPPH° test with EC50 equal to 289.0 ± 1.2 μg/ml. Irradiated (30 kGy) and non-irradiated water extracts had the highest antityrosinase activities with IC50 of 10.8 ± 1.1 and 11.9 ± 1.2 μg phenolic/ml, respectively. In addition, it was found that the water extract of irradiated PGH can prevent enzymatic browning in sliced raw potatoes. According to the antityrosinase potential of PGH extract, it may be suggested as an antibrowning agent in some foodstuffs or cosmetic products.

  4. An appraisal of eighteen commonly consumed edible plants as functional food based on their antioxidant and starch hydrolase inhibitory activities.

    Science.gov (United States)

    Lee, Yian Hoon; Choo, Candy; Watawana, Mindani I; Jayawardena, Nilakshi; Waisundara, Viduranga Y

    2015-11-01

    Eighteen edible plants were assessed for their antioxidant potential based on oxygen radical absorbance capacity (ORAC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, total phenolics, vitamin C content and various lipophilic antioxidants. The inhibitory activities of the plant extracts against the enzymatic activities of α-amylase and α-glucosidase were also evaluated. The antioxidant and starch hydrolase activities of the plants varied widely across a single batch of analysis. The ORAC and DPPH radical scavenging EC50 values varied between 298 and 1984 Trolox equivalents g(-1) fresh weight and between 91 and 533 mg kg(-1) fresh weight, respectively. The total phenolics and vitamin C contents varied between 32 and 125 mg gallic acid equivalents g(-1) fresh weight and between 96 and 285 µg g(-1) fresh weight, respectively. All the plants contained neoxanthin, violaxanthin, and α- and β-carotene in varying amounts. Coccinia grandis, Asparagus racemosus, Costus speciosus, Amaranthus viridis and Annona muricata displayed the highest inhibitory activities against starch hydrolases. They were the most efficient against the breakdown of seven starches exposed to the two enzymes as well. Overall, the edible plants were observed to display a high antioxidant potential with starch hydrolase inhibitory properties, which were beneficial in their being recognized as functional food. © 2014 Society of Chemical Industry.

  5. Tartrazine and sunset yellow are xenoestrogens in a new screening assay to identify modulators of human oestrogen receptor transcriptional activity

    International Nuclear Information System (INIS)

    Axon, Andrew; May, Felicity E.B.; Gaughan, Luke E.; Williams, Faith M.; Blain, Peter G.; Wright, Matthew C.

    2012-01-01

    Primary biliary cirrhosis (PBC) is a cholestatic liver disease of unknown cause that occurs most frequently in post-menopausal women. Since the female sex hormone oestrogen can be cholestatic, we hypothesised that PBC may be triggered in part by chronic exposure to xenoestrogens (which may be more active on a background of low endogenous oestrogen levels seen in post-menopausal women). A reporter gene construct employing a synthetic oestrogen response element predicted to specifically interact with oestrogen receptors (ER) was constructed. Co-transfection of this reporter into an ER null cell line with a variety of nuclear receptor expression constructs indicated that the reporter gene was trans-activated by ERα and ERβ, but not by the androgen, thyroid, progesterone, glucocorticoid or vitamin D receptors. Chemicals linked to PBC were then screened for xenoestrogen activity in the human ERα-positive MCF-7 breast cancer cell line. Using this assay, the coal-derived food and cosmetic colourings – sunset yellow and tartrazine – were identified as novel human ERα activators, activating the human ER with an EC 50% concentration of 220 and 160 nM, respectively.

  6. Tartrazine and sunset yellow are xenoestrogens in a new screening assay to identify modulators of human oestrogen receptor transcriptional activity.

    Science.gov (United States)

    Axon, Andrew; May, Felicity E B; Gaughan, Luke E; Williams, Faith M; Blain, Peter G; Wright, Matthew C

    2012-08-16

    Primary biliary cirrhosis (PBC) is a cholestatic liver disease of unknown cause that occurs most frequently in post-menopausal women. Since the female sex hormone oestrogen can be cholestatic, we hypothesised that PBC may be triggered in part by chronic exposure to xenoestrogens (which may be more active on a background of low endogenous oestrogen levels seen in post-menopausal women). A reporter gene construct employing a synthetic oestrogen response element predicted to specifically interact with oestrogen receptors (ER) was constructed. Co-transfection of this reporter into an ER null cell line with a variety of nuclear receptor expression constructs indicated that the reporter gene was trans-activated by ERα and ERβ, but not by the androgen, thyroid, progesterone, glucocorticoid or vitamin D receptors. Chemicals linked to PBC were then screened for xenoestrogen activity in the human ERα-positive MCF-7 breast cancer cell line. Using this assay, the coal-derived food and cosmetic colourings--sunset yellow and tartrazine--were identified as novel human ERα activators, activating the human ER with an EC(50%) concentration of 220 and 160 nM, respectively. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  7. Influence of metabolism on endocrine activities of bisphenol S.

    Science.gov (United States)

    Skledar, Darja Gramec; Schmidt, Jan; Fic, Anja; Klopčič, Ivana; Trontelj, Jurij; Dolenc, Marija Sollner; Finel, Moshe; Mašič, Lucija Peterlin

    2016-08-01

    Bisphenol S (BPS; bis[4-hydroxyphenyl]sulfone) is commonly used as a replacement for bisphenol A in numerous consumer products. The main goal of this study was to examine the influence of different metabolic reactions that BPS undergoes on the endocrine activity. We demonstrate that hydroxylation of the aromatic ring of BPS, catalyzed mainly by the cytochrome P450 enzymes CYP3A4 and CYP2C9, is its major in-vitro phase I biotransformation. Nevertheless, coupled oxidative-conjugative reactions analyses revealed that glucuronidation and formation of BPS glucuronide is the predominant BPS metabolic pathway. BPS reactive metabolites that can be tracked as glutathione conjugates were not detected in the present study. Two in-vitro systems were used to evaluate the endocrine activity of BPS and its two main metabolites, BPS glucuronide and hydroxylated BPS 4-(4-hydroxy-benzenesulfonyl)-benzene-1,2-diol (BPSM1). In addition, we have tested two structural analogs of BPS, bis[4-(2-hydroxyetoxy)phenyl]sulfone (BHEPS) and 4,4-sulfonylbis(2-methylphenol) (dBPS). The test systems were yeast cells, for evaluating estrogenic and androgenic activities, and the GH3.TRE-Luc reporter cell line for measuring thyroid hormone activity. BPS and BPSM1 were weak agonists of the estrogen receptor, EC50 values of 8.4 × 10(-5) M and 6.7 × 10(-4) M, respectively. Additionally, BPSM1 exhibited weak antagonistic activity toward the thyroid hormone receptor, with an IC50 of 4.3 × 10(-5) M. In contrast to BPSM1, BPS glucuronide was inactive in these assays, inhibiting neither the estrogen nor the thyroid hormone receptors. Hence, glucuronidation appears to be the most important pathway for both BPS metabolism and detoxification. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Chemical composition and antioxidant activity of berry fruits

    Directory of Open Access Journals (Sweden)

    Stajčić Slađana M.

    2012-01-01

    Full Text Available The main chemical composition, contents of total phenolic (TPh, total flavonoid (TF, and total monomeric anthocyianin (TMA, as well as the antioxidant activity of two raspberry cultivars (Meeker and Willamette, two blackberry cultivars (Čačanska bestrna and Thornfree and wild bilberry were studied. The raspberry cultivars had the highest total solids among fruits investigated. Bilberry fruits had the highest sugar-to-acid ratio. Blackberry fruits were richer in crude fibers (cellulose in comparison to raspberry and bilberry fruits. The content of pectic substances was highest in the bilberry. Also, bilberry had a highest content of TPh (808.12 mg GAE/100 g FW, TF (716.31 mg RE/100 g FW and TMA (447.83 mg CGE/100 g FW. The antioxidant activity was evaluated spectrophotometrically, using 2,2-diphenyl-1-picrylhydrazyl (DPPH radical scavenging activity assay. The DPPH free radical scavenging activity, expressed as the EC50 value (in mg of fresh weight of berry fruit per ml of the reaction mixture, of bilberry (0.3157 ± 0.0145 mg/ml was the highest. These results also showed that the antioxidant value of 100 g FW bilberry, raspberry - Willamette, raspberry - Meeker, blackberry - Čačanska bestrna and blackberry - Thornfree is equivalent to 576.50 mg, 282.74 mg, 191.58 mg, 222.28 mg and 272.01 mg of vitamin C, respectively. There was a significant positive correlation between the antioxidant activities and content of total phenolics (RTPh 2=0.9627, flavonoids (RTF 2=0.9598 and anthocyanins (RTMA 2=0.9496 in berry fruits. [Projekat Ministarstva nauke Republike Srbije, br. TR 31044

  9. Chemical analysis of phenolic compounds and determination of anti-oxidant, antimicrobial and cytotoxic activities of organic extracts of Pinus coulteri

    Directory of Open Access Journals (Sweden)

    Soumia Merah

    2018-05-01

    Full Text Available New bioactive natural products, the phenolic composition and the biological activities of organic extracts from the needles of the Algerian Pinus coulteri were investigated. The analysis by HPLC-DAD of crude extract revealed the presence of 10 phenolic acids and nine flavonoids. In vitro anti-oxidant activities were performed using four different tests. The greatest antiradical activity was found in the ethyl acetate fraction (IC50 = 3.2 ± 0.3 µg/mL, whereas the diethyl ether fraction had the higher contents of total phenolics and flavonoids and exhibited a highest activity in reducing power and β-carotene–linoleic acid tests with EC50= 67.1 ± 0.4 μg/mL and 71.5 ± 0.2% of inhibition, respectively. Furthermore, a low to moderate antimicrobial activity according to all extracts was revealed against eight bacteria tested. The MIC value of chloroform fraction showed a strong degree of antibacterial activity (<0.09 mg/mL. The crude extract was found toxic with LC50 value of 15.2 μg/mL by brine shrimp toxicity assay. The needle extract of P. coulteri is rich in valuable biologically active compounds and could represent a new resource of anti-oxidant agents for the treatment of diseases.

  10. Antimicrobial and antioxidant activities and chemical characterization of essential oils of Thymusvulgaris, Rosmarinus officinalis, and Origanum majorana from northeastern México.

    Science.gov (United States)

    Guerra-Boone, Laura; Alvarez-Román, Rocío; Alvarez-Román, Rocío; Salazar-Aranda, Ricardo; Torres-Cirio, Anabel; Rivas-Galindo, Verónica Mayela; de-Torres, Noemí Waksman; González, Gloria; Pérez-López, Luis Alejandro

    2015-01-01

    There have been no reports of antifungal activity and composition of extracts from Thymus vulgaris, Rosmarinus officinalis or Origanum majorana from northeastern México. Antifungal activity of these oils against Trichophyton rubrum, Trichophyton tonsurans, Trichophyton mentagrophytes, Microsporum gypseum, Microsporum canis and Epidermophyton floccosum was measured by diffusion assay. Additionally, antibacterial and antioxidant activities were evaluated. Antibacterial activity against Staphylococcus aureus and Streptococcus pyogenes was examined by microdilution. Antioxidant activity was assessed by 2,2-difenil-1-picrilhidracil reduction test. The plant oils were characterized by both GC/MS and GC/FID. Oils of T. vulgaris and O. majorana showed growth inhibition activity against dermatophytes, especially T. vulgaris oil, which completely inhibited growth of all tested dermatophytes. The oils also showed bioactivity against bacteria, with minimum inhibitory concentration (MIC) values between 62.5 and 500 μg/mL. The antioxidant activity of the oils was low, with effective concentration (EC50) values oils were as follows: T. vulgaris, o-cymene, μ-terpinene, thymol and carvacrol; R. officinalis, terpinen-4-ol and 1,8-cineole; O. majorana, terpinen-4-ol and thymol.

  11. Effect of steeping temperature on antioxidant and inhibitory activities of green tea extracts against α-amylase, α-glucosidase and intestinal glucose uptake.

    Science.gov (United States)

    Liu, Shuyuan; Ai, Zeyi; Qu, Fengfeng; Chen, Yuqiong; Ni, Dejiang

    2017-11-01

    The objective of the present study was to evaluate the effect of steeping temperature on the biological activities of green tea, including the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging capacity, α-glucosidase and α-amylase inhibitory activities, and glucose uptake inhibitory activity in Caco-2 cells. Results showed that, with increasing extraction temperature, the polyphenol content increased, which contributed to enhance antioxidant activity and inhibitory effects on α-glucosidase and α-amylase. Green tea steeped at 100°C showed the highest DPPH radical-scavenging activity and inhibitory effects on α-glucosidase and α-amylase activities with EC 50 or IC 50 values of 6.15μg/mL, 0.09mg/mL, and 6.31mg/mL, respectively. However, the inhibitory potential on glucose uptake did not show an upward trend with increasing extraction temperature. Green tea steeped at 60°C had significantly stronger glucose uptake inhibitory activity (ptea. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Spirocyclic chromanes exhibit antiplasmodial activities and inhibit all intraerythrocytic life cycle stages.

    Science.gov (United States)

    Roberts, Bracken F; Iyamu, Iredia D; Lee, Sukjun; Lee, Eunyoung; Ayong, Lawrence; Kyle, Dennis E; Yuan, Yu; Manetsch, Roman; Chakrabarti, Debopam

    2016-04-01

    We screened a collection of synthetic compounds consisting of natural-product-like substructural motifs to identify a spirocyclic chromane as a novel antiplasmodial pharmacophore using an unbiased cell-based assay. The most active spirocyclic compound UCF 201 exhibits a 50% effective concentration (EC50) of 350 nM against the chloroquine-resistant Dd2 strain and a selectivity over 50 using human liver HepG2 cells. Our analyses of physicochemical properties of UCF 201 showed that it is in compliance with Lipinski's parameters and has an acceptable physicochemical profile. We have performed a limited structure-activity-relationship study with commercially available chromanes preserving the spirocyclic motif. Our evaluation of stage specificities of UCF 201 indicated that the compound is early-acting in blocking parasite development at ring, trophozoite and schizont stages of development as well as merozoite invasion. SPC is an attractive lead candidate scaffold because of its ability to act on all stages of parasite's aexual life cycle unlike current antimalarials.

  13. Chemical structure and antioxidant activity of a new exopolysaccharide produced from Micrococcus luteus

    Directory of Open Access Journals (Sweden)

    Mohsen Mohamed Selim Asker

    2014-12-01

    Full Text Available An exopolysaccharide (EPS reaching a maximum of 13 g/L was isolated from Micrococcus luteus by ethanol precipitation. The crude EPS was purified by chromatography on DEAE-cellulose and Sephacryl S-200, affording a polysaccharide active fraction (AEP with a molecular weight of ∼137 kDa. AEP was investigated by a combination of chemical and chromatographic methods including FTIR, HPLC, periodate oxidation, methylation and GC–MS. Data obtained indicated that AEP was composed of mannose, arabinose, glucose and glucuronic acid in a molar ratio of 3.6:2.7:2.1:1.0, respectively. The main backbone consists of mannose units linked with (1→6-glycosidic bonds and arabinose units linked with (1→5-glycosidic bonds. There is a side chain consisting of mannose units linked with (1→6-glycosidic bonds at C3, when all glucose and most of glucuronic acid are found in the side chain. The in vitro antioxidant assay showed that AEP possesses DPPH radical-scavenging activity, with an EC50 value of 180 μg/mL.

  14. Isolation, purification and antioxidant activity of polysaccharides from the leaves of maca (Lepidium Meyenii).

    Science.gov (United States)

    Caicai, Kang; Limin, Hao; Liming, Zhang; Zhiqiang, Zheng; Yongwu, Yang

    2018-02-01

    Two fractions of polysaccharides (MLP-1 and MLP-2) were extracted from the leaves of maca (Lepidium Meyenii Walp.) by water, and purified using DEAE-52 ion exchange resin and sephadex G-200 clumns chromatography. An investigation was carried out for their structural characterization and antioxidant activity in vitro. The results indicated that MLP-1 was mainly composed of ribose, rhamnose, arabinose, xylose, mannose, glucose and galactose, with the molar ratio of 0.12:0.32:1.50:0.32:1.03:1.00:0.93; the MLP-2 was a homopolysaccharide composed of glucose. The molecular weight (Mw) of MLP-1 was 42756Da, and the Mw of MLP-2 was 93541Da. The FT-IR spectra showed the general characteristic absorption peak of maca leaf polysaccharides (MLPs). The evaluation of antioxidant activity revealed that MLP-1 had strong scavenging effects in vitro on hydroxyl, superoxide anion and DPPH radicals, whose EC 50 (mg/mL) was 0.44, 0.21, and 0.82, respectively. Both MLP-1 and MLP-2 presented dose-dependently positive effects on the antioxidant-related parameters. The results suggested that the purified MLP-1 displayed better antioxidant capacities than that of MLP-1, which could be explored as potential antioxidant agents for the complementary medicine or functional foods. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. In Vitro Antimicrobial Activity of Gel Containing the Herbal Ball Extract against Propionibacterium acnes

    Directory of Open Access Journals (Sweden)

    Chutima Jantarat

    2018-02-01

    Full Text Available The herbal ball has been used as a Thai traditional medicine for relieving many diseases including acne. However, the application process of the herbal ball in practice is complicated and time consuming. The objective of this work was to utilize an herbal ball extract to formulate a gel to reach a more favorable use of the herbal ball for acne treatment. An herbal ball consisting of Andrographis paniculata, Centella asiatica, the Benchalokawichian remedy and the stem bark powder of Hesperethusa crenulata was prepared. The obtained herbal ball was steamed and squeezed to obtain the extract. Gel formulations containing the herbal ball extract at concentrations of 0.1, 1 and 5% w/w were prepared based on a carbomer gel. The herbal ball extract had antioxidant (EC50 = 219.27 ± 36.98 μg/mL and anti Propionibacterium acnes activities (minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC = 31.25 μg/mL. The 5% w/w gel formulation had antimicrobial activity against P. acnes, showing an inhibition zone value of 10.00 ± 1.00 mm. This indicates that the developed gel formulation has potential for acne treatment. In comparison to the traditional method of herbal ball usage, the application of herbal ball extract in the form of gel should be more convenient to use.

  16. Gastroprotective activity of the chloroform extract of the roots from Arctium lappa L.

    Science.gov (United States)

    Dos Santos, Ana C; Baggio, Cristiane H; Freitas, Cristina S; Lepieszynski, Juliana; Mayer, Bárbara; Twardowschy, André; Missau, Fabiana C; dos Santos, Elide P; Pizzolatti, Moacir G; Marques, Maria C A

    2008-06-01

    Arctium lappa L. is used in folk medicine as a diuretic, depurative and digestive stimulant and in dermatological conditions. The objective of this study was to evaluate the effect and the possible mechanisms involved in the gastroprotective effects of a chloroform extract (CE) of the roots from A. lappa and its fractions. Oral pretreatment with CE (10, 30 and 100 mg kg(-1)) significantly reduced gastric lesions induced by ethanol by 61%, 70% and 76%, respectively. Oral administration of CE (100 mg kg(-1) per day for 7 days) reduced the chronic gastric ulceration induced by acetic acid by 52%. Intraduodenal CE (100, 300 and 600 mg kg(-1)) reduced the total acidity of gastric secretion by 22%, 22% and 33%, respectively, while i.p. administration (10, 30 and 100 mg kg(-1)) inhibited total acidity by 50%, 60% and 67%, respectively. In-vitro, CE inhibited H+, K+ -ATPase activity with an EC50 of 53 microgmL(-1) and fraction A (30 and 100 microgmL(-1)) reduced this by 48% and 89%, respectively. CE had no effect on gastrointestinal motility. CE (250 microgmL(-1)) and fraction B (100 and 250 microgmL(-1)) had free-radical scavenging ability, inhibiting 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical activity by 50%, 20% and 55%, respectively. Collectively, the results show that the CE protects animals from gastric lesions by reducing gastric acid secretion via inhibition of gastric H+, K+ -ATPase.

  17. Zebra Mussel Antifouling Activity of the Marine Natural Product Aaptamine and Analogs

    Science.gov (United States)

    Diers, Jeffrey A.; Bowling, John J.; Duke, Stephen O.; Wahyuono, Subagus; Kelly, Michelle; Hamann, Mark T.

    2016-01-01

    Several aaptamine derivatives were selected as potential zebra mussel (Dreissena polymorpha) antifoulants because of the noteworthy absence of fouling observed on Aaptos sponges. Sponges of the genus Aaptos collected in Manado, Indonesia consistently produce aaptamine-type alkaloids. To date, aaptamine and its derivatives have not been carefully evaluated for their antifoulant properties. Structure–activity relationship studies were conducted using several aaptamine derivatives in a zebra mussel antifouling assay. From these data, three analogs have shown significant antifouling activity against zebra mussel attachment. Aaptamine, isoaaptamine, and the demethylated aaptamine compounds used in the zebra mussel assay produced EC50 values of 24.2, 11.6, and 18.6 μM, respectively. In addition, neither aaptamine nor isoaaptamine produced a phytotoxic response (as high as 300 μM) toward a nontarget organism, Lemna pausicostata, in a 7-day exposure. The use of these aaptamine derivatives from Aaptos sp. as potential environmentally benign antifouling alternatives to metal-based paints and preservatives is significant, not only as a possible control of fouling organisms, but also to highlight the ecological importance of these and similar biochemical defenses. PMID:16718618

  18. NPACT: Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database.

    Science.gov (United States)

    Mangal, Manu; Sagar, Parul; Singh, Harinder; Raghava, Gajendra P S; Agarwal, Subhash M

    2013-01-01

    Plant-derived molecules have been highly valued by biomedical researchers and pharmaceutical companies for developing drugs, as they are thought to be optimized during evolution. Therefore, we have collected and compiled a central resource Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database (NPACT, http://crdd.osdd.net/raghava/npact/) that gathers the information related to experimentally validated plant-derived natural compounds exhibiting anti-cancerous activity (in vitro and in vivo), to complement the other databases. It currently contains 1574 compound entries, and each record provides information on their structure, manually curated published data on in vitro and in vivo experiments along with reference for users referral, inhibitory values (IC(50)/ED(50)/EC(50)/GI(50)), properties (physical, elemental and topological), cancer types, cell lines, protein targets, commercial suppliers and drug likeness of compounds. NPACT can easily be browsed or queried using various options, and an online similarity tool has also been made available. Further, to facilitate retrieval of existing data, each record is hyperlinked to similar databases like SuperNatural, Herbal Ingredients' Targets, Comparative Toxicogenomics Database, PubChem and NCI-60 GI(50) data.

  19. Antioxidant, Anti-Nephrolithe Activities and in Vitro Digestibility Studies of Three Different Cyanobacterial Pigment Extracts

    Directory of Open Access Journals (Sweden)

    Chetan Paliwal

    2015-08-01

    Full Text Available Phycobiliprotein-containing water and carotenoid-containing methanolic extracts of three different cyanobacteria, Pseudanabaena sp., Spirulina sp. and Lyngbya sp., were studied for their DPPH scavenging, iso-bolographic studies, and anti-nephrolithe activities. The best EC50 values for DPPH scavenging were in Lyngbya water (LW, 18.78 ± 1.57 mg·mg−1 DPPH and Lyngbya methanol (LM, 59.56 ± 37.38 mg·mg−1 DPPH extracts. Iso-bolographic analysis revealed most of the combinations of extracts were antagonistic to each other, although LM—Spirulina methanol (SM 1:1 had the highest synergistic rate of 86.65%. In vitro digestion studies showed that DPPH scavenging activity was considerably decreased in all extracts except for Pseudanabaena methanol (PM and LM after the simulated digestion. All of the extracts were effective in reducing the calcium oxalate crystal size by nearly 60%–65% compared to negative control, while PM and Spirulina water (SW extracts could inhibit both nucleation and aggregation of calcium oxalate by nearly 60%–80%.

  20. Preparation, characterization and antioxidant activity of polysaccharide from spent Lentinus edodes substrate.

    Science.gov (United States)

    Zhu, Hongji; Tian, Li; Zhang, Lei; Bi, Jingxiu; Song, Qianqian; Yang, Hui; Qiao, Jianjun

    2018-06-01

    This study explored the potential of spent Lentinus edodes substrate, a by-product of mushroom industries causing environmental pollution, serving as materials to produce antioxidant polysaccharide. The extraction process of spent Lentinus edodes substrate polysaccharide (SLSP) was optimized and the effects of drying methods on chemical composition, morphological property and antioxidant activity were investigated. Results showed that freeze-dried SLSP (SLSP-F) exhibited the best quality in terms of the polysaccharide yield (13.00%) and antioxidant activity. The EC 50 values of SLSP-F on DPPH, ABTS and superoxide anion radicals was 0.051mg/mL, 0.379mg/mL, 0.719mg/mL, respectively, which was significantly lower than that of freeze-dried Lentinus edodes polysaccharide (LP-F). After purification by Sephadex G-150, the purified SLSP-F (PSP) has a molecular weight of 16.77kDa. Compared with LP-F, PSP has more reducing sugars and uronic acids in chemical composition and higher contents of xylose, glucose and galactose in monosaccharide composition. FT-IR and NMR spectroscopy analysis revealed that PSP has both α and β glycosidic bonds and massive acetyl groups, which is different from LP-F mainly composed of 1, 3 linked α-D-Manp residue with some acetyl groups. The findings provided a reliable approach for the development of antioxidant polysaccharide from spent Lentinus edodes substrate. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. NPACT: Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database

    Science.gov (United States)

    Mangal, Manu; Sagar, Parul; Singh, Harinder; Raghava, Gajendra P. S.; Agarwal, Subhash M.

    2013-01-01

    Plant-derived molecules have been highly valued by biomedical researchers and pharmaceutical companies for developing drugs, as they are thought to be optimized during evolution. Therefore, we have collected and compiled a central resource Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database (NPACT, http://crdd.osdd.net/raghava/npact/) that gathers the information related to experimentally validated plant-derived natural compounds exhibiting anti-cancerous activity (in vitro and in vivo), to complement the other databases. It currently contains 1574 compound entries, and each record provides information on their structure, manually curated published data on in vitro and in vivo experiments along with reference for users referral, inhibitory values (IC50/ED50/EC50/GI50), properties (physical, elemental and topological), cancer types, cell lines, protein targets, commercial suppliers and drug likeness of compounds. NPACT can easily be browsed or queried using various options, and an online similarity tool has also been made available. Further, to facilitate retrieval of existing data, each record is hyperlinked to similar databases like SuperNatural, Herbal Ingredients’ Targets, Comparative Toxicogenomics Database, PubChem and NCI-60 GI50 data. PMID:23203877

  2. Antifeedant effect of polygodial and drimenol derivatives against Spodoptera frugiperda and Epilachna paenulata and quantitative structure-activity analysis.

    Science.gov (United States)

    Montenegro, Iván J; Del Corral, Soledad; Diaz Napal, Georgina N; Carpinella, María C; Mellado, Marco; Madrid, Alejandro M; Villena, Joan; Palacios, Sara M; Cuellar, Mauricio A

    2018-01-08

    The antifeedant activity of 18 sesquiterpenoids of the drimane family (polygodial, drimenol and derivatives) was investigated. Polygodial, drimanic and nordrimanic derivatives were found to exert antifeedant effects against two insect species, Spodoptera frugiperda and Epilachna paenulata, which are pests of agronomic interest, indicating that they have potential as biopesticide agents. Among the 18 compounds tested, the epoxynordrimane compound (11) and isonordrimenone (4) showed the highest activity [50% effective concentration (EC 50 ) = 23.28 and 25.63 nmol cm - 2 , respectively, against S. frugiperda, and 50.50 and 59.00 nmol/cm 2 , respectively, against E. paenulata]. The results suggest that drimanic compounds have potential as new agents against S. frugiperda and E. paenulata. A quantitative structure-activity relationship (QSAR) analysis of the whole series, supported by electronic studies, suggested that drimanic compounds have structural features necessary for increasing antifeedant activity, namely a C-9 carbonyl group and an epoxide at C-8 and C-9. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

  3. Protective effects of kaempferol against reactive oxygen species-induced hemolysis and its antiproliferative activity on human cancer cells.

    Science.gov (United States)

    Liao, Wenzhen; Chen, Luying; Ma, Xiang; Jiao, Rui; Li, Xiaofeng; Wang, Yong

    2016-05-23

    The protective effects of kaempferol against reactive oxygen species (ROS)-induced hemolysis and its antiproliferative activity on human cancer cells were evaluated in this study. Kaempferol exhibited strong cellular antioxidant ability (CAA) with a CAA value of 59.80 ± 0.379 μM of quercetin (QE)/100 μM (EC50 = 7.74 ± 0.049 μM). Pretreatment with kaempferol significantly attenuated the ROS-induced hemolysis of human erythrocyte (87.4% hemolysis suppressed at 100 μg/mL) and reduced the accumulation of toxic lipid peroxidation product malondialdehyde (MDA). The anti-hemolytic activity of kaempferol was mainly through scavenging excessive ROS and preserving the intrinsic antioxidant enzymes (superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GPx) activities in normal levels. Additionally, kaempferol showed significant antiproliferative activity on a panel of human cancer cell lines including human breast carcinoma (MCF-7) cells, human stomach carcinoma (SGC-7901) cells, human cervical carcinoma (Hela) cells and human lung carcinoma (A549) cells. Kaemperol induced apoptosis of MCF-7 cells accompanied with nuclear condensation and mitochondria dysfunction. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  4. Bioavailability of Antibiotics at Soil-Water Interfaces: A Comparison of Measured Activities and Equilibrium Partitioning Estimates.

    Science.gov (United States)

    Menz, Jakob; Müller, Julia; Olsson, Oliver; Kümmerer, Klaus

    2018-06-05

    There are growing concerns that antibiotic pollution impacts environmental microbiota and facilitates the propagation of antibiotic resistance. However, the prediction or analytical determination of bioavailable concentrations of antibiotics in soil is still subject to great uncertainty. Biological assays are increasingly recognized as valuable complementary tools that allow a more direct determination of the residual antibiotic activity. This study assessed the bioavailability of structurally diverse antibiotics at a soil-water interface applying activity-based analyses in conjunction with equilibrium partitioning (EqP) modeling. The activity against Gram-positive and Gram-negative bacteria of nine antibiotics from different classes was determined in the presence and absence of standard soil (LUFA St. 2.2). The addition of soil affected the activity of different antibiotics to highly varying degrees. Moreover, a highly significant correlation ( p < 0.0001) between the experimentally observed and the EqP-derived log EC 50 (half-maximal effective concentration) values was observed. The innovative experimental design of this study provided new insights on the bioavailability of antibiotics at soil-water interfaces. EqP appears to be applicable to a broad range of antibiotics for the purpose of screening-level risk assessment. However, EqP estimates cannot replace soil-specific ecotoxicity testing in higher-tier assessments, since their accuracy is still compromised by a number of factors.

  5. Hibiscus sabdariffa L. and Its Bioactive Constituents Exhibit Antiviral Activity against HSV-2 and Anti-enzymatic Properties against Urease by an ESI-MS Based Assay

    Directory of Open Access Journals (Sweden)

    Sherif T. S. Hassan

    2017-04-01

    Full Text Available For decades, Hibiscus sabdariffa L. and its phytochemicals have been shown to possess a wide range of pharmacologic properties. In this study, aqueous extract of Hibiscus sabdariffa (AEHS and its bioactive constituent protocatechuic acid (PCA, have been evaluated in vitro for their antiviral activity against HSV-2 clinical isolates and anti-enzymatic activity against urease. Antiherpetic activity was evaluated by the titer reduction assay in infected Vero cells, and cytotoxicity was evaluated by the neutral red dye-uptake method. Anti-urease activity was determined by a developed Electrospray Ionization-Mass Spectrometry (ESI-MS-based assay. PCA showed potent anti-HSV-2 activity compared with that of acyclovir, with EC50 values of 0.92 and 1.43 µg∙mL−1, respectively, and selectivity indices > 217 and > 140, respectively. For the first time, AEHS was shown to exert anti-urease inhibition activity, with an IC50 value of 82.4 µg∙mL−1. This, combined with its safety, could facilitate its use in practical applications as a natural urease inhibitor. Our results present Hibiscus sabdariffa L. and its bioactive compound PCA as potential therapeutic agents in the treatment of HSV-2 infection and the treatment of diseases caused by urease-producing bacteria.

  6. Hibiscus sabdariffa L. and Its Bioactive Constituents Exhibit Antiviral Activity against HSV-2 and Anti-enzymatic Properties against Urease by an ESI-MS Based Assay.

    Science.gov (United States)

    Hassan, Sherif T S; Švajdlenka, Emil; Berchová-Bímová, Kateřina

    2017-04-30

    For decades, Hibiscus sabdariffa L. and its phytochemicals have been shown to possess a wide range of pharmacologic properties. In this study, aqueous extract of Hibiscus sabdariffa (AEHS) and its bioactive constituent protocatechuic acid (PCA), have been evaluated in vitro for their antiviral activity against HSV-2 clinical isolates and anti-enzymatic activity against urease. Antiherpetic activity was evaluated by the titer reduction assay in infected Vero cells, and cytotoxicity was evaluated by the neutral red dye-uptake method. Anti-urease activity was determined by a developed Electrospray Ionization-Mass Spectrometry (ESI-MS)-based assay. PCA showed potent anti-HSV-2 activity compared with that of acyclovir, with EC 50 values of 0.92 and 1.43 µg∙mL -1 , respectively, and selectivity indices > 217 and > 140, respectively. For the first time, AEHS was shown to exert anti-urease inhibition activity, with an IC 50 value of 82.4 µg∙mL -1 . This, combined with its safety, could facilitate its use in practical applications as a natural urease inhibitor. Our results present Hibiscus sabdariffa L. and its bioactive compound PCA as potential therapeutic agents in the treatment of HSV-2 infection and the treatment of diseases caused by urease-producing bacteria.

  7. Group I mGlu receptor stimulation inhibits activation-induced cell death of human T lymphocytes

    Science.gov (United States)

    Chiocchetti, Annalisa; Miglio, Gianluca; Mesturini, Riccardo; Varsaldi, Federica; Mocellin, Marco; Orilieri, Elisabetta; Dianzani, Chiara; Fantozzi, Roberto; Dianzani, Umberto; Lombardi, Grazia

    2006-01-01

    The effects of L-glutamate on activation-induced cell death (AICD) of human activated (1 μg ml−1 phytohemagglutinin plus 2 U ml−1 interleukin-2; 8 days) T lymphocytes were studied by measuring anti-CD3 monoclonal antibody (10 μg ml−1; 18 h)-induced cell apoptosis (Annexin V and propidium iodide staining). L-Glutamate (1 × 10−8–1 × 10−4 M) significantly (P⩽0.01) inhibited AICD in a concentration-dependent manner (EC50=6.3 × 10−8 M; maximum inhibition 54.8±6.3% at 1 × 10−6 M). The L-glutamate inhibitory effect was pharmacologically characterized as mediated by group I mGlu receptors, since mGlu receptor agonists reproduced this effect. The EC50 values were: 3.2 × 10−7 M for (1S,3R)-ACPD; 4.5 × 10−8 M for quisqualate; 1.0 × 10−6 M for (S)-3,5-DHPG; 2.0 × 10−5 M for CHPG. Group I mGlu receptor antagonists inhibited the effects of quisqualate 1.0 × 10−6 M. The IC50 values calculated were: 8.7 × 10−5, 4.3 × 10−6 and 6.3 × 10−7 M for AIDA, LY 367385 and MPEP, respectively. L-Glutamate (1 × 10−6 M; 18 h) significantly (P⩽0.05) inhibited FasL expression (40.8±11.3%) (cytofluorimetric analysis), whereas it did not affect Fas signalling. Expression of both mGlu1 and mGlu5 receptor mRNA by T lymphocytes and T-cell lines, as demonstrated by reverse transcriptase–PCR analysis, suggests that L-glutamate-mediated inhibition of AICD was exerted on T cells. These data depict a novel role for L-glutamate in the regulation of the immune response through group I mGlu receptor-mediated mechanisms. PMID:16751798

  8. Antiviral activity of the extracts of Rhodophyceae from Morocco

    African Journals Online (AJOL)

    Administrator

    2010-11-15

    Nov 15, 2010 ... replication of HSV-1 in vitro at an EC50 (Effective Concentration 50%) ranging from <2.5 to 75.9 µg mL-1. No cytotoxic effect ... Keywords: Antiviral, Aqueous extracts, Organic extracts, Rhodophyceae, Herpes simplex virus. INTRODUCTION ... from a species of Bryopsis as a possible treatment of lung cancer ...

  9. Activation of Glycine and Extrasynaptic GABAA Receptors by Taurine on the Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis

    Directory of Open Access Journals (Sweden)

    Thi Thanh Hoang Nguyen

    2013-01-01

    Full Text Available The substantia gelatinosa (SG of the trigeminal subnucleus caudalis (Vc has been known for the processing and transmission of orofacial nociceptive information. Taurine, one of the most plentiful free amino-acids in humans, has proved to be involved in pain modulation. In this study, using whole-cell patch clamp technique, we investigated the direct membrane effects of taurine and the action mechanism behind taurine-mediated responses on the SG neurons of the Vc. Taurine showed non-desensitizing and repeatable membrane depolarizations and inward currents which remained in the presence of amino-acid receptors blocking cocktail (AARBC with tetrodotoxin, indicating that taurine acts directly on the postsynaptic SG neurons. Further, application of taurine at different doses (10 μM to 3 mM showed a concentration dependent depolarizations and inward currents with the EC50 of 84.3 μM and 723 μM, respectively. Taurine-mediated responses were partially blocked by picrotoxin (50 μM and almost completely blocked by strychnine (2 μM, suggesting that taurine-mediated responses are via glycine receptor (GlyR activation. In addition, taurine (1 mM activated extrasynaptic GABAA receptor (GABAAR-mediated currents. Taken together, our results indicate that taurine can be a target molecule for orofacial pain modulation through the activation of GlyRs and/or extrasynaptic GABAARs on the SG neurons.

  10. Nutritional composition and antioxidant activity of four tomato (Lycopersicon esculentum L.) farmer' varieties in Northeastern Portugal homegardens.

    Science.gov (United States)

    Pinela, José; Barros, Lillian; Carvalho, Ana Maria; Ferreira, Isabel C F R

    2012-03-01

    The nutritional and antioxidant composition of four tomato Portuguese farmer' varieties widely cultivated in homegardens was determined. The analysed components included macronutrients, individual profiles of sugars and fatty acids by chromatographic techniques, hydrophilic antioxidants such as vitamin C, phenolics, flavonols and anthocyanins, and lipophilic antioxidants such as tocopherols, β-carotene and lycopene. Furthermore, the antioxidant activity was evaluated through DPPH scavenging activity, reducing power, β-carotene bleaching inhibition and TBARS formation inhibition. One of the four varieties, which is locally known as round tomato or potato tomato, proved to be the most powerful in antioxidant activity (EC50 values≤1.63 mg/ml), phenolic compounds (phenolics 31.23 mg ClAE/g extract, flavonols 6.36 mg QE/g extract and anthocyanins 3.45 mg ME/g extract) and carotenoids (β-carotene 0.51 mg/100 g and lycopene 9.49 mg/100 g), while the so-called yellow tomato variety revealed interesting nutritional composition, including higher fructose (3.42 g/100 g), glucose (3.18 g/100 g), α-linolenic acid (15.53%) and total tocopherols (1.44 mg/100 g) levels. Overall, these farmer' varieties of garden tomato cultivated in the Northeastern Portuguese region could contribute as sources of important antioxidants related to the prevention of chronic diseases associated to oxidative stress, such as cancer and coronary artery disease. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Activation of Glycine and Extrasynaptic GABAA Receptors by Taurine on the Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis

    Science.gov (United States)

    Bhattarai, Janardhan Prasad; Park, Soo Joung; Han, Seong Kyu

    2013-01-01

    The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) has been known for the processing and transmission of orofacial nociceptive information. Taurine, one of the most plentiful free amino-acids in humans, has proved to be involved in pain modulation. In this study, using whole-cell patch clamp technique, we investigated the direct membrane effects of taurine and the action mechanism behind taurine-mediated responses on the SG neurons of the Vc. Taurine showed non-desensitizing and repeatable membrane depolarizations and inward currents which remained in the presence of amino-acid receptors blocking cocktail (AARBC) with tetrodotoxin, indicating that taurine acts directly on the postsynaptic SG neurons. Further, application of taurine at different doses (10 μM to 3 mM) showed a concentration dependent depolarizations and inward currents with the EC50 of 84.3 μM and 723 μM, respectively. Taurine-mediated responses were partially blocked by picrotoxin (50 μM) and almost completely blocked by strychnine (2 μM), suggesting that taurine-mediated responses are via glycine receptor (GlyR) activation. In addition, taurine (1 mM) activated extrasynaptic GABAA receptor (GABAAR)-mediated currents. Taken together, our results indicate that taurine can be a target molecule for orofacial pain modulation through the activation of GlyRs and/or extrasynaptic GABAARs on the SG neurons. PMID:24379976

  12. Development of a novel LC/MS method to quantitate cellular stearoyl-CoA desaturase activity

    International Nuclear Information System (INIS)

    Dillon, Roslyn; Greig, Michael J.; Bhat, B. Ganesh

    2008-01-01

    Stearoyl-CoA desaturase 1 (SCD1) is an enzyme that catalyzes the rate-limiting step in de novo synthesis of monounsaturated fatty acids-mainly oleate and palmitoleate from stearoyl-CoA and palmitoyl-Co A, respectively. These products are the most abundant monounsaturated fatty acids in membrane phospholipids, triglycerides, cholesterol esters. Reports on mice with a targeted disruption of SCD1 gene (SCD1-/-) exhibit improved glucose tolerance and insulin sensitivity compared to wild-type suggesting SCD1 could be a therapeutic target for diabetes and related metabolic diseases. Measurement of SCD1 activity is technically challenging and traditional cell-based SCD1 assay procedure is labor intensive with low throughput. We describe here a novel medium-throughput LC/MS cell-based assay for determining cellular SCD1 activity, facilitating screening of potential SCD1 inhibitor compounds. Confluent HepG2 cells were grown in 24-well plates and incubated with vehicle or an inhibitor followed by incubation with deuterium labeled saturated fatty acid substrates. Total cell lipids were extracted and the conversion of stearate to oleate was measured by liquid chromatography-mass spectrometry. Sterculate, a known inhibitor of SCD1, inhibited the enzyme activity in a dose dependent manner in this assay with a calculated EC 50 of 247 nM. The medium-throughput method described here is an important step towards identifying an inhibitor of SCD1 to treat diabetes and related metabolic diseases

  13. Potent Antifouling Marine Dihydroquinolin-2(1H)-one-Containing Alkaloids from the Gorgonian Coral-Derived Fungus Scopulariopsis sp.

    Science.gov (United States)

    Shao, Chang-Lun; Xu, Ru-Fang; Wang, Chang-Yun; Qian, Pei-Yuan; Wang, Kai-Ling; Wei, Mei-Yan

    2015-08-01

    Marine biofouling has a major economic impact, especially when it occurs on ship hulls or aquaculture facilities. Since the International Maritime Organization (IMO) treaty to ban the application of organotin-based paints to ships went into effect in 2008, there is an urgent demand for the development of efficient and environmentally friendly antifouling agents. Marine microorganisms have proved to be a potential source of antifouling natural compounds. In this study, six dihydroquinolin-2-one-containing alkaloids, three monoterpenoids combined with a 4-phenyl-3,4-dihydroquinolin-2(1H)-one (1-3) and three 4-phenyl-3,4-dihydroquinolin-2(1H)-one alkaloids (4-6), were isolated from the gorgonian coral-derived fungus Scopulariopsis sp. collected in the South China Sea. These dihydroquinolin-2-one-containing alkaloids were evaluated against the larval settlement of barnacle Balanus amphitrite, and antifouling activity was detected for the first time for this class of metabolites. All of them except 6 showed strong antifouling activity. Compounds 1 and 2 were discovered to be the most promising non-toxic antilarval settlement candidates. Especially, compound 1 is the strongest antifouling compound in nature until now which showed highly potent activity with picomolar level (EC50 17.5 pM) and a very safety and high therapeutic ratio (LC50/EC50 1200). This represents an effective non-toxic, anti-larval settlement structural class of promising antifouling lead compound.

  14. Sulfated polysaccharides with antioxidant and anticoagulant activity from the sea cucumber Holothuria fuscogliva

    Science.gov (United States)

    Li, Rongfeng; Yu, Huahua; Yue, Yang; Liu, Song; Xing, Rong'e.; Chen, Xiaolin; Li, Pengcheng

    2017-07-01

    Sea cucumber is a traditional nutritional food and medicinal resource with many bioactive components in China. Holothuria fuscogliva is a big sea cucumber with a rich of bioactive polysaccharides. To investigate the bioactivities of the polysaccharides from sea cucumber H. fuscogliva, we prepared the sulfated polysaccharides (HfP) from sea cucumber H. fuscogliva using a protease hydrolysis method. Antioxidant activities of HfP were investigated, including hydroxyl radical scavenging activity and superoxide radical scavenging activity. And, the anticoagulant activities of HfP were studied, including the activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT). The average molecular weight was 1 867.1 Da, with a sulfate content of 20.7%. In addition, the molar ratio of monosaccharide composition of HfP was Man: Rha: Glc A: Glc: Gal: Xyl: Fuc=0.083 6: 0.437: 0.134: 0:1.182: 0.748: 1. It had a strong antioxidant activity, the hydroxyl and superoxide radical scavenging activity EC50 of HfP was 3.74 and 0.037 mg/mL, respectively. It also showed a good anticoagulant activity in our study. The APTT of HfP was much higher than that of heparin sodium, and the PT and TT of HfP was close to that of heparin sodium at a low concentration. Therefore, HfP shows a good antioxidant and anticoagulant activity and it may become a potential candidate of the natural antioxidant and anticoagulant and will have a good application future in health product or medicine industry.

  15. Additive and synergistic antiandrogenic activities of mixtures of azol fungicides and vinclozolin

    International Nuclear Information System (INIS)

    Christen, Verena; Crettaz, Pierre; Fent, Karl

    2014-01-01

    Objective: Many pesticides including pyrethroids and azole fungicides are suspected to have an endocrine disrupting property. At present, the joint activity of compound mixtures is only marginally known. Here we tested the hypothesis that the antiandrogenic activity of mixtures of azole fungicides can be predicted by the concentration addition (CA) model. Methods: The antiandrogenic activity was assessed in MDA-kb2 cells. Following assessing single compounds activities mixtures of azole fungicides and vinclozolin were investigated. Interactions were analyzed by direct comparison between experimental and estimated dose–response curves assuming CA, followed by an analysis by the isobole method and the toxic unit approach. Results: The antiandrogenic activity of pyrethroids deltamethrin, cypermethrin, fenvalerate and permethrin was weak, while the azole fungicides tebuconazole, propiconazole, epoxiconazole, econazole and vinclozolin exhibited strong antiandrogenic activity. Ten binary and one ternary mixture combinations of five antiandrogenic fungicides were assessed at equi-effective concentrations of EC 25 and EC 50 . Isoboles indicated that about 50% of the binary mixtures were additive and 50% synergistic. Synergism was even more frequently indicated by the toxic unit approach. Conclusion: Our data lead to the conclusion that interactions in mixtures follow the CA model. However, a surprisingly high percentage of synergistic interactions occurred. Therefore, the mixture activity of antiandrogenic azole fungicides is at least additive. Practice: Mixtures should also be considered for additive antiandrogenic activity in hazard and risk assessment. Implications: Our evaluation provides an appropriate “proof of concept”, but whether it equally translates to in vivo effects should further be investigated. - Highlights: • Humans are exposed to pesticide mixtures such as pyrethroids and azole fungicides. • We assessed the antiandrogenicity of pyrethroids and

  16. HPTLC-profiling of eleutherosides, mechanism of antioxidative action of eleutheroside E1, the PAMPA test with LC/MS detection and the structure–activity relationship

    Directory of Open Access Journals (Sweden)

    Daniel Załuski

    2018-03-01

    Full Text Available Human body is constantly generating free radicals, which causes oxidative stress. Despite naturally occurring antioxidant systems in human body, free radicals cause lipid, proteins and DNA oxidation. New antioxidants are still urgent as well as their mechanisms of action should be explained. In this study, we investigated the mechanism by which eleutherosides B, E and E1 may act as antioxidants, identified eleutherosides in Eleutherococcus lasiogyne and Eleutherococcus giraldii, and explained in vitro the absorption of eleutheroside E1 based on passive transport. The DPPH∗ and DB-HPTLC tests were used to assess the antioxidant activity. Of the three eleutherosides, only eleutheroside E1 exhibited a strong anti-DPPH∗ activity (EC50 37.03 μg/mL; 63 mMol compared to the raw extracts (EC50 170 and 180 μg/mL for E. lasiogyne and E. giraldii. This activity was also confirmed by the DB-HPTLC autography technique. According to Załuski’s hypothesis, the antioxidant mechanism of eleutheroside E1 is based on the complexation of DPPH∗ molecule with its aryl radical. During this reaction, the aryl radical of eleutheroside E1 (E1∗ and DPPHH are created. Next, the aryl radical (E1∗ is complexed with another DPPH∗ molecule. Additionally, the aryl radical can be stabilized by the presence of the methoxy groups in the aromatic ring, which increases its antioxidative action. The HPTLC-identification of extracts showed the presence of eleutherosides B, E and E1 in both species. The PAMPA test coupled with LC/MS detection showed a low permeability of eleutheroside E1 across artificial membrane. Because eleutherosides belong to the polyphenols, the TPC and TFC were quantified. The TPC and TFC varied from 51.4 to 49.3 mg/g dry extract for TPC, and from 5.73 to 4.91 mg/g dry extract for TFC, for E. giraldii and E. lasiogyne, respectively. In conclusion, eleutheroside E1 in its pure form could be a chemopreventive ingredient of new pharmacological

  17. Cytotoxic, Anti-Proliferative and Apoptosis Activity of l-Amino Acid Oxidase from Malaysian Cryptelytrops purpureomaculatus (CP-LAAO) Venom on Human Colon Cancer Cells.

    Science.gov (United States)

    Zainal Abidin, Syafiq Asnawi; Rajadurai, Pathmanathan; Hoque Chowdhury, Md Ezharul; Othman, Iekhsan; Naidu, Rakesh

    2018-06-08

    The aim of this study is to investigate the potential anti-cancer activity of l-amino acid oxidase (CP-LAAO) purified from the venom of Cryptelytrops purpureomaculatus on SW480 and SW620 human colon cancer cells. Mass spectrometry guided purification was able to identify and purify CP-LAAO. Amino acid variations identified from the partial protein sequence of CP-LAAO may suggest novel variants of these proteins. The activity of the purified CP-LAAO was confirmed with o-phenyldiamine (OPD)-based spectrophotometric assay. CP-LAAO demonstrated time- and dose-dependent cytotoxic activity and the EC 50 value was determined at 13 µg/mL for both SW480 and SW620 cells. Significant increase of caspase-3 activity, reduction of Bcl-2 levels, as well as morphological changes consistent with apoptosis were demonstrated by CP-LAAO. Overall, these data provide evidence on the potential anti-cancer activity of CP-LAAO from the venom of Malaysian C. purpureomaculatus for therapeutic intervention of human colon cancer.

  18. Synthesis, Antimicrobial, Antioxidant and Nematicidal Activity of (2E,4E)-5-(Benzo(d) (1,3)dioxol-5yl)penta-2,4-dienamides

    International Nuclear Information System (INIS)

    Wahab, A.; Sultana, A.; Sherwani, S. K.; Perveen, Z.; Khan, K. M.; Karim, A.; Taha, M.

    2015-01-01

    The amides of piperic acid have been synthesized via the condensation of piperic acid with amines. The structural characterization was done by IR, 1H-NMR, EI-MS and elemental analysis. The amides 3a-3o were evaluated for their biological activity. It has been found that among others the newly synthesized compound 3f, 3k, 3m, and 3o have great potential against root-knot nematode Meloidogyne incognita that usually affect tomato crop. These compounds exhibited 92, 96, 82 and 95% mortality rate at lethal concentration (LC50) 4.4, 3.4, 4.5 and 3.5 mg/mL, respectively. Conventionally used nematicide furadan was taken as standard. Compound 3h, 3c and, 3j exhibited significant anti-oxidant activities against 1,1-diphenylpicrylhydrazil (DPPH) radical with 80, 70 and 72% inhibition (EC50 = 625, 937 and 937.5 micro g/mL), respectively. Ascorbic acid was used as standard. When tested for antimicrobial activity 3m was found to be the most active one showing zone of inhibition in the range of 18-30 mm against all tested microbial strains. Good biological activities of synthetic amides indicate their ability to behave as a good antimicrobial and nematicidal agent. (author)

  19. In vitro Effects of Four Native Brazilian Medicinal Plants in CYP3A4 mRNA Gene Expression, Glutathione Levels, and P-Glycoprotein Activity.

    Science.gov (United States)

    Mazzari, Andre L D A; Milton, Flora; Frangos, Samantha; Carvalho, Ana C B; Silveira, Dâmaris; de Assis Rocha Neves, Francisco; Prieto, Jose M

    2016-01-01

    Erythrina mulungu Benth. (Fabaceae), Cordia verbenacea A. DC. (Boraginaceae), Solanum paniculatum L. (Solanaceae) and Lippia sidoides Cham. (Verbenaceae) are medicinal plant species native to Brazil shortlisted by the Brazilian National Health System for future clinical use. However, nothing is known about their effects in metabolic and transporter proteins, which could potentially lead to herb-drug interactions (HDI). In this work, we assess non-toxic concentrations (100 μg/mL) of the plant infusions for their in vitro ability to modulate CYP3A4 mRNA gene expression and intracellular glutathione levels in HepG2 cells, as well as P-glycoprotein (P-gp) activity in vincristine-resistant Caco-2 cells (Caco-2 VCR). Their mechanisms of action were further studied by measuring the activation of human pregnane X receptor (hPXR) in transiently co-transfected HeLa cells and the inhibition of γ-glutamyl transferase (GGT) in HepG2 cells. Our results show that P-gp activity was not affected in any case and that only Solanum paniculatum was able to significantly change CYP3A4 mRNA gene expression (twofold decrease, p effect upon hPXR (EC50 = 0.38 mg/mL). Total intracellular glutathione levels were significantly depleted by exposure to Solanum paniculatum (-44%, p Cordia verbenacea (-47%, p activity (-48%, p active pharmacovigilance is recommended for the other three species, especially in the case of Solanum paniculatum.

  20. Antifungal activity of the osthol derivative JS-B against Phytophthora capsici.

    Science.gov (United States)

    Wang, Chun-Mei; Guan, Wei; Fang, Shu; Chen, Hao; Li, You-Qin; Cai, Chun; Fan, Yong-Jian; Shi, Zhi-Qi

    2010-08-01

    JS-B (C(12)H(10)O(3)) is a derivative compound of osthol. The antifungal properties of JS-B were tested against 10 economically important plant pathogens. JS-B was effective in inhibiting the mycelial growth of Phytophthora capsici, and its inhibition on different stages of the life cycle of P. capsici was observed. The 50% effective concentration (EC(50)) of JS-B on mycelial dry weight and zoospore germination of P. capsici was 43.74 and 86.03 microg/ml, respectively. The rupture of released zoospores induced by JS-B was reduced by the addition of 100 mM glucose. The ultrastructural study showed that JS-B caused destruction of most of the mitochondrions, the concentration of cell nuclear, and the existing vesicles. When compared with dimethomorph, the activity of JS-B on P. capsici was determined under pot conditions. The result showed that JS-B has a curative effect on pepper blight.

  1. Activated sludge respirometry to assess solar detoxification of a metal finishing effluent

    International Nuclear Information System (INIS)

    Santos-Juanes, L.; Amat, A.M.; Arques, A.; Bernabeu, A.; Silvestre, M.; Vicente, R.; Ano, E.

    2008-01-01

    Inhibition of the respiration of activated sludge has been tested as a convenient method to estimate toxicity of aqueous solutions containing copper and cyanide, such as metal finishing effluents; according to this method, an EC 50 of 0.5 mg/l was determined for CN - and 3.0 mg/l for copper. Solar detoxification of cyanide-containing solutions was studied using TiO 2 , but this process was unfavourable because of the inhibitory role that plays the copper ions present in real effluents on the oxidation of cyanide. On the other hand, the oxidative effect of hydrogen peroxide was greatly enhanced by Cu 2+ and solar irradiation, as complete elimination of free and complexed cyanide could be accomplished, together with precipitation of copper, in experiments carried out at pilot plant scale with real metal finishing effluents. Under these conditions, total detoxification was achieved according to respirometric measurements although some remaining toxicity was determined by more sensitive Vibrio fischeri luminescent assay

  2. Structurally related hydrazone-based metal complexes with different antitumor activities variably induce apoptotic cell death.

    Science.gov (United States)

    Megger, Dominik A; Rosowski, Kristin; Radunsky, Christian; Kösters, Jutta; Sitek, Barbara; Müller, Jens

    2017-04-05

    Three new complexes bearing the tridentate hydrazone-based ligand 2-(2-(1-(pyridin-2-yl)ethylidene)hydrazinyl)pyridine (L) were synthesized and structurally characterized. Biological tests indicate that the Zn(ii) complex [ZnCl 2 (L)] is of low cytotoxicity against the hepatocellular carcinoma cell line HepG2. In contrast, the Cu(ii) and Mn(ii) complexes [CuCl 2 (L)] and [MnCl 2 (L)] are highly cytotoxic with EC 50 values of 1.25 ± 0.01 μM and 20 ± 1 μM, respectively. A quantitative proteome analysis reveals that treatment of the cells with the Cu(ii) complex leads to a significantly altered abundance of 102 apoptosis-related proteins, whereas 38 proteins were up- or down-regulated by the Mn(ii) complex. A closer inspection of those proteins regulated only by the Cu(ii) complex suggests that the superior cytotoxic activity of this complex is likely to be related to an initiation of the caspase-independent cell death (CICD). In addition, an increased generation of reactive oxygen species (ROS) and a strong up-regulation of proteins responsive to oxidative stress suggest that alterations of the cellular redox metabolism likely contribute to the cytotoxicity of the Cu(ii) complex.

  3. N-Formylated humanin activates both formyl peptide receptor-like 1 and 2

    International Nuclear Information System (INIS)

    Harada, Masataka; Habata, Yugo; Hosoya, Masaki; Nishi, Kazunori; Fujii, Ryo; Kobayashi, Makoto; Hinuma, Shuji

    2004-01-01

    We have discovered that humanin (HN) acts as a ligand for formyl peptide receptor-like 1 (FPRL1) and 2 (FPRL2). This discovery was based on our finding that HN suppressed forskolin-induced cAMP production in Chinese hamster ovary (CHO) cells expressing human FPRL1 (CHO-hFPRL1) or human FPRL2 (CHO-hFPRL2). In addition, we found that N-formylated HN (fHN) performed more potently as a ligand for FPRL1 than HN: in CHO-hFPRL1 cells, the effective concentration for the half-maximal response (EC 50 ) value of HN was 3.5 nM, while that of fHN was 0.012 nM. We demonstrated by binding experiments using [ 125 I]-W peptide that HN and fHN directly interacted with hFPRL1 on the membrane. In addition, we found that HN and fHN showed strong chemotactic activity for CHO-hFPRL1 and CHO-hFPRL2 cells. HN is known to have a protective effect against neuronal cell death. Our findings contribute to the understanding of the mechanism behind HN's function

  4. Antileishmanial activity evaluation of adunchalcone, a new prenylated dihydrochalcone from Piper aduncum L.

    Science.gov (United States)

    Dal Picolo, Camilla R; Bezerra, Mariana P; Gomes, Kaio S; Passero, Luiz Felipe D; Laurenti, Marcia D; Martins, Euder Glendes A; Sartorelli, Patricia; Lago, João Henrique G

    2014-09-01

    Bioactivity-guided fractionation of EtOH extract from the leaves of Piper aduncum L. (Piperaceae) afforded a new dihydrochalcone, named adunchalcone. Its structure was elucidated on the basis of their spectroscopic data, primarily NMR and MS. Adunchalcone was evaluated against promastigote forms of Leishmania (L.) amazonensis, L. (V.) braziliensis, L. (V.) shawi, and L. (L.) chagasi and displayed 50% effective concentrations (EC50) of 11.03, 26.70, and 11.26 μM, as well as selective indexes of 4.86, 2.01, 4.76 and 0.50, respectively. This compound was also tested against intracellular forms of L. (L.) amazonensis, displaying weak activity, in comparison to reference drug amphotericin B. However, despite reduced effect of adunchalcone against amastigotes of L. (L.) amazonensis, this work opens the perspective to use this particular molecule as a scaffold for the design of novel and selective drug candidates for neglected diseases, mainly leishmaniasis. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Aortic Relaxant Activity of Crataegus gracilior Phipps and Identification of Some of Its Chemical Constituents

    Directory of Open Access Journals (Sweden)

    Abigail Hernández-Pérez

    2014-12-01

    Full Text Available This study focused on the assessment of the vasorelaxant activity of the organic and aqueous extracts obtained from leaves and fruits of a Mexican hawthorn (Crataegus gracilior on isolated rat aorta, and on the purification and identification of some of their secondary metabolites by the use of chromatographic and spectroscopic techniques. The results obtained showed that the methanol extract has a significantly more potent and effective vasorelaxant effect than the other tested extracts, with an EC50 = 8.69 ± 4.34 µg/mL and an Emax = 94.6% ± 11.30%, values that are close to that of acetylcholine, the positive control. From the same extract, two major triterpenes were isolated and identified as ursolic and corosolic acids by comparison of their experimental NMR spectroscopic data with those reported in the literature. Chlorogenic acid, rutin, quercetin, kaempferol and (+-catechin were also identified using HPLC coupled with PDAD. All these compounds have already been proven to possess on their own antihypertensive effect and other benefits on cardiovascular diseases and they can support, at least in part, the traditional use of this plant species.

  6. Quantitative structure-activity relationships for green algae growth inhibition by polymer particles.

    Science.gov (United States)

    Nolte, Tom M; Peijnenburg, Willie J G M; Hendriks, A Jan; van de Meent, Dik

    2017-07-01

    After use and disposal of chemical products, many types of polymer particles end up in the aquatic environment with potential toxic effects to primary producers like green algae. In this study, we have developed Quantitative Structure-Activity Relationships (QSARs) for a set of highly structural diverse polymers which are capable to estimate green algae growth inhibition (EC50). The model (N = 43, R 2  = 0.73, RMSE = 0.28) is a regression-based decision tree using one structural descriptor for each of three polymer classes separated based on charge. The QSAR is applicable to linear homo polymers as well as copolymers and does not require information on the size of the polymer particle or underlying core material. Highly branched polymers, non-nitrogen cationic polymers and polymeric surfactants are not included in the model and thus cannot be evaluated. The model works best for cationic and non-ionic polymers for which cellular adsorption, disruption of the cell wall and photosynthesis inhibition were the mechanisms of action. For anionic polymers, specific properties of the polymer and test characteristics need to be known for detailed assessment. The data and QSAR results for anionic polymers, when combined with molecular dynamics simulations indicated that nutrient depletion is likely the dominant mode of toxicity. Nutrient depletion in turn, is determined by the non-linear interplay between polymer charge density and backbone flexibility. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. The Fungicidal Activity of Thymol against Fusarium graminearum via Inducing Lipid Peroxidation and Disrupting Ergosterol Biosynthesis

    Directory of Open Access Journals (Sweden)

    Tao Gao

    2016-06-01

    Full Text Available Thymol is a natural plant-derived compound that has been widely used in pharmaceutical and food preservation applications. However, the antifungal mechanism for thymol against phytopathogens remains unclear. In this study, we identified the antifungal action of thymol against Fusarium graminearum, an economically important phytopathogen showing severe resistance to traditional chemical fungicides. The sensitivity of thymol on different F. graminearum isolates was screened. The hyphal growth, as well as conidial production and germination, were quantified under thymol treatment. Histochemical, microscopic, and biochemical approaches were applied to investigate thymol-induced cell membrane damage. The average EC50 value of thymol for 59 F. graminearum isolates was 26.3 μg·mL−1. Thymol strongly inhibited conidial production and hyphal growth. Thymol-induced cell membrane damage was indicated by propidium iodide (PI staining, morphological observation, relative conductivity, and glycerol measurement. Thymol induced a significant increase in malondialdehyde (MDA concentration and a remarkable decrease in ergosterol content. Taken together, thymol showed potential antifungal activity against F. graminearum due to the cell membrane damage originating from lipid peroxidation and the disturbance of ergosterol biosynthesis. These results not only shed new light on the antifungal mechanism of thymol, but also imply a promising alternative for the control of Fusarium head blight (FHB disease caused by F. graminearum.

  8. Tea and herbal infusions: Their antioxidant activity and phenolic profile

    International Nuclear Information System (INIS)

    Atoui, A.; Mansouri, A.; Panagiotis Kefalas; Boskou, G.

    2005-01-01

    Tea and herbal infusions have been studied for their polyphenolic content, antioxidant activity and phenolic profile. The total phenolics recovered by ethyl acetate from the water extract, were determined by the Folin-Ciocalteu procedure and ranged from 88.1 ± 0.42 (Greek mountain tea) to 1216 ± 32.0 mg (Chinese green tea) GAE (Gallic acid equivalents)/cup. The antioxidant activity was evaluated by two methods, DPPH and chemiluminescence assays, using Trolox and quercetin as standards. The EC50 of herbal extracts ranged from 0.151 ± 0.002 mg extract/mg DPPH (0.38 quercetin equivalents and 0.57 Trolox equivalents), for Chinese green tea, to 0.77 ± 0.012 mg extract/mg DPPH (0.08 quercetin equivalents and 0.13 Trolox equivalents), for Greek mountain tea. Chemiluminescence assay results showed that the IC50 ranged from 0.17 ± 3.4 x 103 lg extract/ml of the final solution in the measuring cell (1.89 quercetin and 5.89 Trolox equivalents) for Chinese green tea, to 1.10 ± 1.86 x 102 g extract/ml of the final solution in the measuring cell (0.29 quercetin and 0.90 Trolox equivalents) for Greek mountain tea. The phenolic profile in the herbal infusions was investigated by LC-DAD-MS in the positive electrospray ionization (ESI) mode. About 60 different flavo- noids, phenolic acids and their derivatives have been identified. (author)

  9. Glucosidase inhibitory activity and antioxidant activity of flavonoid compound and triterpenoid compound from Agrimonia Pilosa Ledeb.

    Science.gov (United States)

    Liu, Xi; Zhu, Liancai; Tan, Jun; Zhou, Xuemei; Xiao, Ling; Yang, Xian; Wang, Bochu

    2014-01-10

    In Chinese traditional medicine, Agrimonia pilosa Ledeb (APL) exhibits great effect on treatment of type 2 diabetes mellitus (T2DM), however its mechanism is still unknown. Considering that T2DM are correlated with postprandial hyperglycemia and oxidative stress, we investigated the α-glucosidase inhibitory activity and the antioxidant activity of flavonoid compound (FC) and triterpenoid compound (TC) from APL. Entire plants of APL were extracted using 95% ethanol and 50% ethanol successively. The resulting extracts were partitioned and isolated by applying liquid chromatography using silica gel column and Sephadex LH 20 column to give FC and TC. The content of total flavonoids in FC and the content of total triterpenoids in TC were determined by using UV spectrophotometry. HPLC analysis was used to identify and quantify the monomeric compound in FC and TC. The α-glucosidase inhibitory activities were determined using the chromogenic method with p-nitrophenyl-α-D-glucopyranoside as substrate. Antioxidant activities were assessed through three kinds of radical scavenging assays (DPPH radical, ABTS radical and hydroxyl radical) & β-carotene-linoleic acid assay. The results indicate FC is abundant of quercitrin, and hyperoside, and TC is abundant of 1β, 2β, 3β, 19α-tetrahydroxy-12-en-28-oic acid (265.2 mg/g) and corosolic acid (100.9 mg/g). The FC & the TC have strong α-glucosidase inhibitory activities with IC50 of 8.72 μg/mL and 3.67 μg/mL, respectively. We find that FC show competitive inhibition against α-glucosidase, while the TC exhibits noncompetitive inhibition. Furthermore, The FC exhibits significant radical scavenging activity with the EC50 values of 7.73 μg/mL, 3.64 μg/mL and 5.90 μg/mL on DPPH radical, hydroxyl radical and ABTS radical, respectively. The FC also shows moderate anti-lipid peroxidation activity with the IC50 values of 41.77 μg/mL on inhibiting β-carotene bleaching. These results imply that the FC and the TC could be

  10. Nutritional and Chemical Composition and Antiviral Activity of Cultivated Seaweed Sargassum naozhouense Tseng et Lu 

    Directory of Open Access Journals (Sweden)

    Yonghong Liu

    2012-12-01

    Full Text Available Sargassum naozhouense is a brown seaweed used in folk medicine and applied for thousands of years in Zhanjiang, Guangdong province, China. This study is the first time to investigate its chemical composition and antiviral activity. On the dry weight basis, this seaweed was constituted of ca. 35.18% ash, 11.20% protein, 1.06% lipid and 47.73% total carbohydrate, and the main carbohydrate was water-soluble polysaccharide. The protein analysis indicated the presence of essential amino acids, which accounted for 36.35% of the protein. The most abundant fatty acids were C14:0, C16:0, C18:1 and C20:4. The ash fraction analysis indicated that essential minerals and trace elements, such as Fe, Zn and Cu, were present in the seaweed. IR analysis revealed that polysaccharides from cultivated S. naozhouense may be alginates and fucoidan. The polysaccharides possessed strong antiviral activity against HSV-1 in vitro with EC50 of 8.92 μg/mL. These results demonstrated cultivated S. naozhouense has a potential for its use in functional foods and antiviral new drugs.

  11. ATP induces NO production in hippocampal neurons by P2X(7 receptor activation independent of glutamate signaling.

    Directory of Open Access Journals (Sweden)

    Juan Francisco Codocedo

    Full Text Available To assess the putative role of adenosine triphosphate (ATP upon nitric oxide (NO production in the hippocampus, we used as a model both rat hippocampal slices and isolated hippocampal neurons in culture, lacking glial cells. In hippocampal slices, additions of exogenous ATP or 2'(3'-O-(4-Benzoylbenzoyl ATP (Bz-ATP elicited concentration-dependent NO production, which increased linearly within the first 15 min and plateaued thereafter; agonist EC50 values were 50 and 15 µM, respectively. The NO increase evoked by ATP was antagonized in a concentration-dependent manner by Coomassie brilliant blue G (BBG or by N(ω-propyl-L-arginine, suggesting the involvement of P2X7Rs and neuronal NOS, respectively. The ATP induced NO production was independent of N-methyl-D-aspartic acid (NMDA receptor activity as effects were not alleviated by DL-2-Amino-5-phosphonopentanoic acid (APV, but antagonized by BBG. In sum, exogenous ATP elicited NO production in hippocampal neurons independently of NMDA receptor activity.

  12. Acute toxicity and antispasmodic activities of Achillea wilhelmsii C. Koch.

    Science.gov (United States)

    Ali, Niaz; Shah, Syed Wadood Ali; Ahmed, Ghayour; Shah, Ismail; Shoaib, Mohammad; Junaid, Muhammad; Ali, Waqar

    2014-03-01

    Since Achillea wilhelmsii is used as antispasmodic in traditional medicine, we conducted our current work to investigate its rationale on scientific grounds. Acute toxicity studies of crude methanol extract of Achillea wilhelmsii (Aw. CMeOH) is also performed. Effect of Aw. CMeOH and its fractions were tested on isolated sections of rabbits' jejunum at test concentrations 0.01, 0.03, 1.0, 3.0, 5.0 and 10mg/ml. The test extracts, in similar concentrations, were also tested on KCl-induced contractions. Calcium chloride curves were constructed for those fractions which relaxed KCl induced contractions in the absence and presence of the test samples to investigate its possible mode of action through calcium channels. Aw. CMeOH tested positive for flavonoids, saponins, tannins, glycosides, terpenoids, sterols, phenols, carbohydrates and proteins. LD(50) for acute toxicity studies is 2707±12.6 mg/kg. Mean EC(50) values for Aw. CMeOH on spontaneous and KCl-induced contractions are 3.41±0.18 (2.56-3.8, n=6) and 0.68±0.05 (0.6-0.85, n=6) mg/ml, respectively. Respective EC(50) values for n-hexane fraction on spontaneous and KCl-induced contractions are 3.06±0.08 (2.8-3.3, n=6) and 1.68±0.8 (1.4-1.9, n=6) mg/ml, respectively. Corresponding EC(50) (mg/ml) values for chloroformic, ethylacetate and aqueous fractions of Achillea wilhelmsii on spontaneous rabbits' jejunum preparations are 4.8±0.2 (4.41-5.63, n=6), 5.07±0.15 (4.7-5.58, n=6) and 5.2±0.13 (4.91-5.64, n=4), respectively. Constructing calcium chloride curves, in the presence of 0.1 mg/ml of Aw. CMeOH, mean EC(50) value (log molar [Ca(++)]) is-1.98±0.03 (-1.89-2.05, n=6) vs. control EC(50) (log molar [Ca(++)])-2.41±0.02 (-2.32-2.44, n=6). Mean EC(50) value (log molar [Ca(++)]) for 0.3 mg/ml n-hexane fraction is-1.76±0.05 (-1.70 -1.93, n=6) vs. control EC(50) (log molar [Ca(++)]) value-2.18±0.07 (-2.0-2.46, n=6). While in the presence of chloroformic fraction (3 mg/ml), mean EC(50) (log molar [Ca(++)]) value

  13. A high-throughput cellular assay to quantify the p53-degradation activity of E6 from different human papillomavirus types.

    Science.gov (United States)

    Gagnon, David; Archambault, Jacques

    2015-01-01

    A subset of human papillomaviruses (HPVs), known as the high-risk types, are the causative agents of cervical cancer and other malignancies of the anogenital region and oral mucosa. The capacity of these viruses to induce cancer and to immortalize cells in culture relies in part on a critical function of their E6 oncoprotein, that of promoting the poly-ubiquitination of the cellular tumor suppressor protein p53 and its subsequent degradation by the proteasome. Here, we describe a cellular assay to measure the p53-degradation activity of E6 from different HPV types. This assay is based on a translational fusion of p53 to Renilla luciferase (Rluc-p53) that remains sensitive to degradation by high-risk E6 and whose steady-state levels can be accurately measured in standard luciferase assays. The p53-degradation activity of any E6 protein can be tested and quantified in transiently transfected cells by determining the amount of E6-expression vector required to reduce by half the levels of RLuc-p53 luciferase activity (50 % effective concentration [EC50]). The high-throughput and quantitative nature of this assay makes it particularly useful to compare the p53-degradation activities of E6 from several HPV types in parallel.

  14. Cytotoxicity and activation of the Wnt/beta-catenin pathway in mouse embryonic stem cells treated with four GSK3 inhibitors.

    Science.gov (United States)

    Naujok, Ortwin; Lentes, Jana; Diekmann, Ulf; Davenport, Claudia; Lenzen, Sigurd

    2014-04-29

    Small membrane-permeable molecules are now widely used during maintenance and differentiation of embryonic stem cells of different species. In particular the glycogen synthase kinase 3 (GSK3) is an interesting target, since its chemical inhibition activates the Wnt/beta-catenin pathway. In the present comparative study four GSK3 inhibitors were characterized. Cytotoxicity and potential to activate the Wnt/beta-catenin pathway were tested using the commonly used GSK3 inhibitors BIO, SB-216763, CHIR-99021, and CHIR-98014. Wnt/beta-catenin-dependent target genes were measured by quantitative PCR to confirm the Wnt-reporter assay and finally EC50-values were calculated. CHIR-99021 and SB-216763 had the lowest toxicities in mouse embryonic stem cells and CHIR-98014 and BIO the highest toxicities. Only CHIR-99021 and CHIR-98014 lead to a strong induction of the Wnt/beta-catenin pathway, whereas BIO and SB-216763 showed a minor or no increase in activation of the Wnt/beta-catenin pathway over the natural ligand Wnt3a. The data from the Wnt-reporter assay were confirmed by gene expression analysis of the TCF/LEF regulated gene T. Out of the four tested GSK3 inhibitors, only CHIR-99021 and CHIR-98014 proved to be potent pharmacological activators of the Wnt/beta-catenin signaling pathway. But only in the case of CHIR-99021 high potency was combined with very low toxicity.

  15. Synthesis and evaluation of 8,4'-dideshydroxy-leinamycin revealing new insights into the structure-activity relationship of the anticancer natural product leinamycin.

    Science.gov (United States)

    Liu, Tao; Ma, Ming; Ge, Hui-Ming; Yang, Chunying; Cleveland, John; Shen, Ben

    2015-11-01

    Leinamycin (LNM, 1) is a novel antitumor antibiotic produced by Streptomyces atroolivaceus S-140 and features an unusual 1,3-dioxo-1,2-dithiolane moiety that is spiro-fused to a thiazole-containing 18-membered lactam ring. The 1,3-dioxo-1,2-dithiolane moiety of LNM is essential for its antitumor activity via an episulfonium ion-mediated DNA alkylation upon reductive activation in the presence of cellular thiols. We recently isolated leinamycin E1 (LNM E1, 2) from an engineered strain S. atroolivaceus SB3033, which lacks the 1,3-dioxo-1,2-dithiolane moiety. Here we report the chemical synthesis of 8,4'-dideshydroxy-LNM (5) from 2 and determination of the cytotoxicity of 5 against selected cancer cell lines in comparison with 1; 5 exhibits comparable activity as 1 with the EC50 values between 8.21 and 275 nM. This work reveals new insight into the structure-activity relationship of LNM and highlights the synergy between metabolic pathway engineering and medicinal chemistry for natural product drug discovery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Lipid reducing activity and toxicity profiles of a library of polyphenol derivatives.

    Science.gov (United States)

    Urbatzka, Ralph; Freitas, Sara; Palmeira, Andreia; Almeida, Tiago; Moreira, João; Azevedo, Carlos; Afonso, Carlos; Correia-da-Silva, Marta; Sousa, Emilia; Pinto, Madalena; Vasconcelos, Vitor

    2018-05-10

    Obesity is an increasing epidemic worldwide and novel treatments are urgently needed. Polyphenols are natural compounds derived from plants, which are known in particular for their antioxidant properties. However, some polyphenols were described to possess anti-obesity activities in vitro and in vivo. In this study, we aimed to screen a library of 85 polyphenol derivatives for their lipid reducing activity and toxicity. Compounds were analyzed at 5 μM with the zebrafish Nile red fluorescence fat metabolism assay and for general toxicity in vivo. To improve the safety profile, compounds were screened at 50 μM in murine preadipocytes in vitro for cytotoxicity. Obtained activity data were used to create a 2D-QSAR (quantitative structure activity relationship) model. 38 polyphenols showed strong lipid reducing activity. Toxicity analysis revealed that 18 of them did not show any toxicity in vitro or in vivo. QSAR analysis revealed the importance of the number of rings, fractional partial positively charged surface area, relative positive charge, relative number of oxygen atoms, and partial negative surface area for lipid-reducing activity. The five most potent compounds with EC 50 values in the nanomolar range for lipid reducing activity and without any toxic effects are strong candidates for future research and development into anti-obesity drugs. Molecular profiling for fasn, sirt1, mtp and ppary revealed one compound that reduced significantly fasn mRNA expression. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  17. Process, Goal and Social Interaction Differences in Recreation: What Makes an Activity Substitutable.

    Science.gov (United States)

    Baumgartner, Robert; Heberlein, Thomas A.

    Two recreational activities, deer hunting and goose hunting, both similar in form, are compared. It was hypothesized that the activity for which participants rated the process, the goal, and the social interaction as most important to the experience and for which participants showed the strongest family ties and social support for participation…

  18. Evaluation of the Influence of the Macro-environment on the Social Innovation Activity of Enterprises

    Directory of Open Access Journals (Sweden)

    Satalkina Liliya

    2018-02-01

    Full Text Available Background: Nowadays the emphasis on social components in the general mainstream of innovation activity is one of the strongest grounds for the successful functioning and development of enterprises. In several countries, social innovation activity is becoming a product of business in general, with associated expectations regarding profit.

  19. Effect of chromium oxide (III) nanoparticles on the production of reactive oxygen species and photosystem II activity in the green alga Chlamydomonas reinhardtii

    International Nuclear Information System (INIS)

    Costa, Cristina Henning da; Perreault, François; Oukarroum, Abdallah; Melegari, Sílvia Pedroso; Popovic, Radovan; Matias, William Gerson

    2016-01-01

    With the growth of nanotechnology and widespread use of nanomaterials, there is an increasing risk of environmental contamination by nanomaterials. However, the potential implications of such environmental contamination are hard to evaluate since the toxicity of nanomaterials if often not well characterized. The objective of this study was to evaluate the toxicity of a chromium-based nanoparticle, Cr_2O_3-NP, used in a wide diversity of industrial processes and commercial products, on the unicellular green alga Chlamydomonas reinhardtii. The deleterious impacts of Cr_2O_3-NP were characterized using cell density measurements, production of reactive oxygen species (ROS), esterase enzymes activity, and photosystem II electron transport as indicators of toxicity. Cr_2O_3-NP exposure inhibited culture growth and significantly lowered cellular Chlorophyll a content. From cell density measurements, EC50 values of 2.05 ± 0.20 and 1.35 ± 0.06 g L"−"1 Cr_2O_3-NP were obtained after 24 and 72 h of exposure, respectively. In addition, ROS levels were increased to 160.24 ± 2.47% and 59.91 ± 0.15% of the control value after 24 and 72 h of exposition to 10 g L"−"1 Cr_2O_3-NP. At 24 h of exposure, the esterase activity increased to 160.24% of control value, revealing a modification of the short-term metabolic response of algae to Cr_2O_3-NP exposure. In conclusion, the metabolism of C. reinhardtii was the most sensitive to Cr_2O_3-NP after 24 h of treatment. - Highlights: • Cr_2O_3 nanoparticles are unstable and form large aggregates in the medium. • EC50 for growth inhibition of C. reinhardtii is 1.35 g L"−"1 at 72 h. • Cr_2O_3 nanoparticles increase ROS levels at 10 g L"−"1. • Cr_2O_3 nanoparticles affect photosynthetic electron transport.

  20. PAM-1616, a selective peroxisome proliferator-activated receptor γ modulator with preserved anti-diabetic efficacy and reduced adverse effects.

    Science.gov (United States)

    Kim, Mi-Kyung; Chae, Yu Na; Choi, Song-hyen; Moon, Ho Sang; Son, Moon-Ho; Bae, Myung-Ho; Choi, Hyun-ho; Hur, Youn; Kim, Eunkyung; Park, Yoo Hoi; Park, Chan Sun; Kim, Jae Gyu; Lim, Joong In; Shin, Chang Yell

    2011-01-15

    Peroxisome proliferator-activated receptor (PPAR) γ is known to be a key regulator of insulin resistance. PAM-1616 is a novel, non-thiazolidinedione small molecule compound synthesized in Dong-A Research Center. In this study, we characterized the pharmacological and safety profiles of PAM-1616 as a selective PPARγ modulator. PAM-1616 selectively binds to human PPARγ (IC(50), 24.1±5.6 nM) and is a partial agonist for human PPARγ with an EC(50) of 83.6±43.7 nM and a maximal response of 24.9±7.1% relative to the full agonist, rosiglitazone. PAM-1616 was selective for human PPARγ than for human PPARα (EC(50), 2658±828 nM) without activating human PPARδ, which makes it a selective modulator of PPARγ. Treatment of high fat diet-induced obese C57BL/6J mice with PAM-1616 for 21 days improved HOMA-IR. Furthermore, PAM-1616 significantly improved hyperglycemia in db/db mice with little side effect when orally administered at a dose of 1 mg/kg/day for 28 days. Intriguingly, PAM-1616 was seen to increase the gene expression of inducible glucose transporter (GLUT4), while it partially induced that of a fatty acid carrier, aP2 in 3T3-L1 adipocytes, and it also showed partial recruitment of an adipogenic cofactor, TRAP220 as compared to rosiglitazone. PAM-1616 did not cause a significant increase in plasma volume of ICR mice when orally administered at a dose of 10 mg/kg/day for 9 days. PAM-1616 increased the expression of fluid retention-inducing genes such as serum/glucocorticoid-regulated kinase (SGK)-1 to a lesser extent as compared to rosiglitazone in human renal epithelial cells. These results suggest that PAM-1616 acts as a selective modulator of PPARγ with excellent antihyperglycemic property. The differential modulation of target gene by PAM-1616 might contribute to the improved side effect profiles. Copyright © 2010 Elsevier B.V. All rights reserved.

  1. Effect of chromium oxide (III) nanoparticles on the production of reactive oxygen species and photosystem II activity in the green alga Chlamydomonas reinhardtii

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Cristina Henning da [Department of Sanitary and Environmental Engineering, Federal University of Santa Catarina, Campus Universitário, CEP: 88040-970, Florianópolis, SC (Brazil); Perreault, François [School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, AZ 85287-3005 (United States); Oukarroum, Abdallah [Department of Chemistry, University of Quebec in Montréal, 2101, Jeanne Mance Street, Station Centre-Ville, Montréal, QC H2X 2J6 (Canada); Melegari, Sílvia Pedroso [Department of Sanitary and Environmental Engineering, Federal University of Santa Catarina, Campus Universitário, CEP: 88040-970, Florianópolis, SC (Brazil); Center of Marine Studies, Federal University of Parana, Beira-mar Avenue, 83255-976, Pontal do Parana, PR (Brazil); Popovic, Radovan [Department of Chemistry, University of Quebec in Montréal, 2101, Jeanne Mance Street, Station Centre-Ville, Montréal, QC H2X 2J6 (Canada); Matias, William Gerson, E-mail: william.g.matias@ufsc.br [Department of Sanitary and Environmental Engineering, Federal University of Santa Catarina, Campus Universitário, CEP: 88040-970, Florianópolis, SC (Brazil)

    2016-09-15

    With the growth of nanotechnology and widespread use of nanomaterials, there is an increasing risk of environmental contamination by nanomaterials. However, the potential implications of such environmental contamination are hard to evaluate since the toxicity of nanomaterials if often not well characterized. The objective of this study was to evaluate the toxicity of a chromium-based nanoparticle, Cr{sub 2}O{sub 3}-NP, used in a wide diversity of industrial processes and commercial products, on the unicellular green alga Chlamydomonas reinhardtii. The deleterious impacts of Cr{sub 2}O{sub 3}-NP were characterized using cell density measurements, production of reactive oxygen species (ROS), esterase enzymes activity, and photosystem II electron transport as indicators of toxicity. Cr{sub 2}O{sub 3}-NP exposure inhibited culture growth and significantly lowered cellular Chlorophyll a content. From cell density measurements, EC50 values of 2.05 ± 0.20 and 1.35 ± 0.06 g L{sup −1} Cr{sub 2}O{sub 3}-NP were obtained after 24 and 72 h of exposure, respectively. In addition, ROS levels were increased to 160.24 ± 2.47% and 59.91 ± 0.15% of the control value after 24 and 72 h of exposition to 10 g L{sup −1} Cr{sub 2}O{sub 3}-NP. At 24 h of exposure, the esterase activity increased to 160.24% of control value, revealing a modification of the short-term metabolic response of algae to Cr{sub 2}O{sub 3}-NP exposure. In conclusion, the metabolism of C. reinhardtii was the most sensitive to Cr{sub 2}O{sub 3}-NP after 24 h of treatment. - Highlights: • Cr{sub 2}O{sub 3} nanoparticles are unstable and form large aggregates in the medium. • EC50 for growth inhibition of C. reinhardtii is 1.35 g L{sup −1} at 72 h. • Cr{sub 2}O{sub 3} nanoparticles increase ROS levels at 10 g L{sup −1}. • Cr{sub 2}O{sub 3} nanoparticles affect photosynthetic electron transport.

  2. Azidoblebbistatin, a photoreactive myosin inhibitor

    Science.gov (United States)

    Képiró, Miklós; Várkuti, Boglárka H.; Bodor, Andrea; Hegyi, György; Drahos, László; Kovács, Mihály; Málnási-Csizmadia, András

    2012-01-01

    Photoreactive compounds are important tools in life sciences that allow precisely timed covalent crosslinking of ligands and targets. Using a unique technique we have synthesized azidoblebbistatin, which is a derivative of blebbistatin, the most widely used myosin inhibitor. Without UV irradiation azidoblebbistatin exhibits identical inhibitory properties to those of blebbistatin. Using UV irradiation, azidoblebbistatin can be covalently crosslinked to myosin, which greatly enhances its in vitro and in vivo effectiveness. Photo-crosslinking also eliminates limitations associated with the relatively low myosin affinity and water solubility of blebbistatin. The wavelength used for photo-crosslinking is not toxic for cells and tissues, which confers a great advantage in in vivo tests. Because the crosslink results in an irreversible association of the inhibitor to myosin and the irradiation eliminates the residual activity of unbound inhibitor molecules, azidoblebbistatin has a great potential to become a highly effective tool in both structural studies of actomyosin contractility and the investigation of cellular and physiological functions of myosin II. We used azidoblebbistatin to identify previously unknown low-affinity targets of the inhibitor (EC50 ≥ 50 μM) in Dictyostelium discoideum, while the strongest interactant was found to be myosin II (EC50 = 5 μM). Our results demonstrate that azidoblebbistatin, and potentially other azidated drugs, can become highly useful tools for the identification of strong- and weak-binding cellular targets and the determination of the apparent binding affinities in in vivo conditions. PMID:22647605

  3. Profound activity of the anti-cancer drug bortezomib against Echinococcus multilocularis metacestodes identifies the proteasome as a novel drug target for cestodes.

    Directory of Open Access Journals (Sweden)

    Britta Stadelmann

    2014-12-01

    Full Text Available A library of 426 FDA-approved drugs was screened for in vitro activity against E. multilocularis metacestodes employing the phosphoglucose isomerase (PGI assay. Initial screening at 20 µM revealed that 7 drugs induced considerable metacestode damage, and further dose-response studies revealed that bortezomib (BTZ, a proteasome inhibitor developed for the chemotherapy of myeloma, displayed high anti-metacestodal activity with an EC50 of 0.6 µM. BTZ treatment of E. multilocularis metacestodes led to an accumulation of ubiquinated proteins and unequivocally parasite death. In-gel zymography assays using E. multilocularis extracts demonstrated BTZ-mediated inhibition of protease activity in a band of approximately 23 kDa, the same size at which the proteasome subunit beta 5 of E. multilocularis could be detected by Western blot. Balb/c mice experimentally infected with E. multilocularis metacestodes were used to assess BTZ treatment, starting at 6 weeks post-infection by intraperitoneal injection of BTZ. This treatment led to reduced parasite weight, but to a degree that was not statistically significant, and it induced adverse effects such as diarrhea and neurological symptoms. In conclusion, the proteasome was identified as a drug target in E. multilocularis metacestodes that can be efficiently inhibited by BTZ in vitro. However, translation of these findings into in vivo efficacy requires further adjustments of treatment regimens using BTZ, or possibly other proteasome inhibitors.

  4. Novel human topoisomerase I inhibitors, topopyrones A, B, C and D. I. Producing strain, fermentation, isolation, physico-chemical properties and biological activity.

    Science.gov (United States)

    Kanai, Y; Ishiyama, D; Senda, H; Iwatani, W; Takahashi, H; Konno, H; Tokumasu, S; Kanazawa, S

    2000-09-01

    In the course of a screening program for specific inhibitors of human topoisomerase I using a recombinant yeast, we have discovered four new active compounds. All four compounds were isolated from the culture broth of a fungus, Phoma sp. BAUA2861, and two of them were isolated from the culture broth of a fungus, Penicillium sp. BAUA4206. We designated these compounds as topopyrones A, B, C and D. Topopyrones A, B, C and D selectively inhibited recombinant yeast growth dependent on expression of human topoisomerase I with IC50 values of 1.22, 0.15, 4.88 and 19.63 ng/ml, respectively. The activity and selectivity of topopyrone B were comparable to those of camptothecin. The relaxation of supercoiled pBR322 DNA by human DNA topoisomerase I was inhibited by these compounds, however they did not inhibit human DNA topoisomerase II. Topopyrones A, B, C and D were cytotoxic to all tumor cell lines when tested in vitro. Topopyrone B has potent inhibitory activity against herpesvirus, especially varicella zoster virus (VZV). It inhibited VZV growth with EC50 value of 0.038 microg/ml, which is 24-fold stronger than that of acyclovir (0.9 microg/ml). Topopyrones A, B, and C were inhibitory to Gram-positive bacteria.

  5. Antifungal Activity and Action Mode of Cuminic Acid from the Seeds of Cuminum cyminum L. against Fusarium oxysporum f. sp. Niveum (FON Causing Fusarium Wilt on Watermelon

    Directory of Open Access Journals (Sweden)

    Yang Sun

    2017-11-01

    Full Text Available In order to develop a novel biofungicide, the antifungal activity and action mode of cuminic acid from the seed of Cuminum cyminum L. against Fusarium oxysporum f. sp. niveum (FON on watermelon was determined systematically. In this study, the median effective concentration (EC50 value for cuminic acid in inhibiting mycelial growth of FON was 22.53 μg/mL. After treatment with cuminic acid, the mycelial morphology was seriously influenced; cell membrane permeability and glycerol content were increased markedly, but pigment and mycotoxin (mainly fusaric acid were significantly decreased. Synthesis genes of bikaverin (Bike1, Bike2 and Bike3 and fusaric acid (FUB1, FUB2, FUB3 and FUB4 both were downregulated compared with the control, as confirmed by quantitative RT-PCR. In greenhouse experiments, cuminic acid at all concentrations displayed significant bioactivities against FON. Importantly, significant enhancement of activities of SOD, POD, CAT and decrease of MDA content were observed after in vivo cuminic acid treatment on watermelon leaves. These indicated that cuminic acid not only showed high antifungal activity, but also could enhance the self-defense system of the host plant. Above all, cuminic acid showed the potential as a biofungicide to control FON.

  6. Antifungal Activity and Action Mode of Cuminic Acid from the Seeds of Cuminum cyminum L. against Fusarium oxysporum f. sp. Niveum (FON) Causing Fusarium Wilt on Watermelon.

    Science.gov (United States)

    Sun, Yang; Wang, Yong; Han, Li Rong; Zhang, Xing; Feng, Jun Tao

    2017-11-30

    In order to develop a novel biofungicide, the antifungal activity and action mode of cuminic acid from the seed of Cuminum cyminum L. against Fusarium oxysporum f. sp. niveum (FON) on watermelon was determined systematically. In this study, the median effective concentration (EC 50 ) value for cuminic acid in inhibiting mycelial growth of FON was 22.53 μg/mL. After treatment with cuminic acid, the mycelial morphology was seriously influenced; cell membrane permeability and glycerol content were increased markedly, but pigment and mycotoxin (mainly fusaric acid) were significantly decreased. Synthesis genes of bikaverin ( Bike1 , Bike2 and Bike3 ) and fusaric acid ( FUB1 , FUB2 , FUB3 and FUB4 ) both were downregulated compared with the control, as confirmed by quantitative RT-PCR. In greenhouse experiments, cuminic acid at all concentrations displayed significant bioactivities against FON. Importantly, significant enhancement of activities of SOD, POD, CAT and decrease of MDA content were observed after in vivo cuminic acid treatment on watermelon leaves. These indicated that cuminic acid not only showed high antifungal activity, but also could enhance the self-defense system of the host plant. Above all, cuminic acid showed the potential as a biofungicide to control FON.

  7. Antifouling Activity of Synthetic Alkylpyridinium Polymers Using the Barnacle Model

    Science.gov (United States)

    Piazza, Veronica; Dragić, Ivanka; Sepčić, Kristina; Faimali, Marco; Garaventa, Francesca; Turk, Tom; Berne, Sabina

    2014-01-01

    Polymeric alkylpyridinium salts (poly-APS) isolated from the Mediterranean marine sponge, Haliclona (Rhizoniera) sarai, effectively inhibit barnacle larva settlement and natural marine biofilm formation through a non-toxic and reversible mechanism. Potential use of poly-APS-like compounds as antifouling agents led to the chemical synthesis of monomeric and oligomeric 3-alkylpyridinium analogues. However, these are less efficient in settlement assays and have greater toxicity than the natural polymers. Recently, a new chemical synthesis method enabled the production of poly-APS analogues with antibacterial, antifungal and anti-acetylcholinesterase activities. The present study examines the antifouling properties and toxicity of six of these synthetic poly-APS using the barnacle (Amphibalanus amphitrite) as a model (cyprids and II stage nauplii larvae) in settlement, acute and sub-acute toxicity assays. Two compounds, APS8 and APS12-3, show antifouling effects very similar to natural poly-APS, with an anti-settlement effective concentration that inhibits 50% of the cyprid population settlement (EC50) after 24 h of 0.32 mg/L and 0.89 mg/L, respectively. The toxicity of APS8 is negligible, while APS12-3 is three-fold more toxic (24-h LC50: nauplii, 11.60 mg/L; cyprids, 61.13 mg/L) than natural poly-APS. This toxicity of APS12-3 towards nauplii is, however, 60-fold and 1200-fold lower than that of the common co-biocides, Zn- and Cu-pyrithione, respectively. Additionally, exposure to APS12-3 for 24 and 48 h inhibits the naupliar swimming ability with respective IC50 of 4.83 and 1.86 mg/L. PMID:24699112

  8. Antifouling Activity of Synthetic Alkylpyridinium Polymers Using the Barnacle Model

    Directory of Open Access Journals (Sweden)

    Veronica Piazza

    2014-04-01

    Full Text Available Polymeric alkylpyridinium salts (poly-APS isolated from the Mediterranean marine sponge, Haliclona (Rhizoniera sarai, effectively inhibit barnacle larva settlement and natural marine biofilm formation through a non-toxic and reversible mechanism. Potential use of poly-APS-like compounds as antifouling agents led to the chemical synthesis of monomeric and oligomeric 3-alkylpyridinium analogues. However, these are less efficient in settlement assays and have greater toxicity than the natural polymers. Recently, a new chemical synthesis method enabled the production of poly-APS analogues with antibacterial, antifungal and anti-acetylcholinesterase activities. The present study examines the antifouling properties and toxicity of six of these synthetic poly-APS using the barnacle (Amphibalanus amphitrite as a model (cyprids and II stage nauplii larvae in settlement, acute and sub-acute toxicity assays. Two compounds, APS8 and APS12-3, show antifouling effects very similar to natural poly-APS, with an anti-settlement effective concentration that inhibits 50% of the cyprid population settlement (EC50 after 24 h of 0.32 mg/L and 0.89 mg/L, respectively. The toxicity of APS8 is negligible, while APS12-3 is three-fold more toxic (24-h LC50: nauplii, 11.60 mg/L; cyprids, 61.13 mg/L than natural poly-APS. This toxicity of APS12-3 towards nauplii is, however, 60-fold and 1200-fold lower than that of the common co-biocides, Zn- and Cu-pyrithione, respectively. Additionally, exposure to APS12-3 for 24 and 48 h inhibits the naupliar swimming ability with respective IC50 of 4.83 and 1.86 mg/L.

  9. In vitro antioxidant, anti-inflammatory, cytotoxic activities against prostate cancer of extracts from Hibiscus sabdariffa leaves.

    Science.gov (United States)

    Worawattananutai, Patsorn; Itharat, Arunporn; Ruangnoo, Srisopa

    2014-08-01

    Hibiscus sabdariffa (HS) leaves are a vegetable, which is used as a healthy sour soup for protection against chronic diseases in Thai traditional medicine. To investigate antioxidant, anti-inflammatory and cytotoxic activities of Hibiscus sabdariffa leave extracts from diferent extraction methods. Fresh and dry Hibiscus sabdariffa leaves were extracted by various methods such as maceration with 95% and 50% ethanol, squeeze, and boiling with water or decoction. All extracts were testedfor antioxidant activity by using DPPH radical scavenging assay, anti-inflammatory activity by determination on inhibitory effect of nitric oxide production on RAW264. 7 cell. Cytotoxic activity also tested against human prostate cancer cell line (PC-3) by using sulforhodamine B (SRB) assay. Total phenolic content determined by the Folin-Ciocalteu colorimetric method. The results found that the 95% ethanolic extract of Hibiscus sabdariffa dried leaves (HSDE95) showed the highest antioxidant activity with an EC50 of 34.51±2.62 μg/ml and had the highest phenolic content (57.00±3.73 mg GAE/g). HSDE95 also showed potent cytotoxicity against prostate cancer cell line with an IC50 of 8.58±0.68 μg/ml whereas HSDE95 and all of extracts ofHibiscus sabdariffa leaves had no anti-inflammatory activity. The obtained results revealed that HSDE95 extract showedpotent cytotoxic activity against prostate cancer cells but low antioxidant and anti-inflammatory activities. This extract should be further isolated as active compounds against prostate cancer.

  10. Machine learning models identify molecules active against the Ebola virus in vitro [version 3; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2017-01-01

    Full Text Available The search for small molecule inhibitors of Ebola virus (EBOV has led to several high throughput screens over the past 3 years. These have identified a range of FDA-approved active pharmaceutical ingredients (APIs with anti-EBOV activity in vitro and several of which are also active in a mouse infection model. There are millions of additional commercially-available molecules that could be screened for potential activities as anti-EBOV compounds. One way to prioritize compounds for testing is to generate computational models based on the high throughput screening data and then virtually screen compound libraries. In the current study, we have generated Bayesian machine learning models with viral pseudotype entry assay and the EBOV replication assay data. We have validated the models internally and externally. We have also used these models to computationally score the MicroSource library of drugs to select those likely to be potential inhibitors. Three of the highest scoring molecules that were not in the model training sets, quinacrine, pyronaridine and tilorone, were tested in vitro and had EC50 values of 350, 420 and 230 nM, respectively. Pyronaridine is a component of a combination therapy for malaria that was recently approved by the European Medicines Agency, which may make it more readily accessible for clinical testing. Like other known antimalarial drugs active against EBOV, it shares the 4-aminoquinoline scaffold. Tilorone, is an investigational antiviral agent that has shown a broad array of biological activities including cell growth inhibition in cancer cells, antifibrotic properties, α7 nicotinic receptor agonist activity, radioprotective activity and activation of hypoxia inducible factor-1. Quinacrine is an antimalarial but also has use as an anthelmintic. Our results suggest data sets with less than 1,000 molecules can produce validated machine learning models that can in turn be utilized to identify novel EBOV inhibitors in

  11. Machine learning models identify molecules active against the Ebola virus in vitro [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2015-10-01

    Full Text Available The search for small molecule inhibitors of Ebola virus (EBOV has led to several high throughput screens over the past 3 years. These have identified a range of FDA-approved active pharmaceutical ingredients (APIs with anti-EBOV activity in vitro and several of which are also active in a mouse infection model. There are millions of additional commercially-available molecules that could be screened for potential activities as anti-EBOV compounds. One way to prioritize compounds for testing is to generate computational models based on the high throughput screening data and then virtually screen compound libraries. In the current study, we have generated Bayesian machine learning models with viral pseudotype entry assay and the EBOV replication assay data. We have validated the models internally and externally. We have also used these models to computationally score the MicroSource library of drugs to select those likely to be potential inhibitors. Three of the highest scoring molecules that were not in the model training sets, quinacrine, pyronaridine and tilorone, were tested in vitro and had EC50 values of 350, 420 and 230 nM, respectively. Pyronaridine is a component of a combination therapy for malaria that was recently approved by the European Medicines Agency, which may make it more readily accessible for clinical testing. Like other known antimalarial drugs active against EBOV, it shares the 4-aminoquinoline scaffold. Tilorone, is an investigational antiviral agent that has shown a broad array of biological activities including cell growth inhibition in cancer cells, antifibrotic properties, α7 nicotinic receptor agonist activity, radioprotective activity and activation of hypoxia inducible factor-1. Quinacrine is an antimalarial but also has use as an anthelmintic. Our results suggest data sets with less than 1,000 molecules can produce validated machine learning models that can in turn be utilized to identify novel EBOV inhibitors in

  12. Machine learning models identify molecules active against the Ebola virus in vitro [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sean Ekins

    2016-01-01

    Full Text Available The search for small molecule inhibitors of Ebola virus (EBOV has led to several high throughput screens over the past 3 years. These have identified a range of FDA-approved active pharmaceutical ingredients (APIs with anti-EBOV activity in vitro and several of which are also active in a mouse infection model. There are millions of additional commercially-available molecules that could be screened for potential activities as anti-EBOV compounds. One way to prioritize compounds for testing is to generate computational models based on the high throughput screening data and then virtually screen compound libraries. In the current study, we have generated Bayesian machine learning models with viral pseudotype entry assay and the EBOV replication assay data. We have validated the models internally and externally. We have also used these models to computationally score the MicroSource library of drugs to select those likely to be potential inhibitors. Three of the highest scoring molecules that were not in the model training sets, quinacrine, pyronaridine and tilorone, were tested in vitro and had EC50 values of 350, 420 and 230 nM, respectively. Pyronaridine is a component of a combination therapy for malaria that was recently approved by the European Medicines Agency, which may make it more readily accessible for clinical testing. Like other known antimalarial drugs active against EBOV, it shares the 4-aminoquinoline scaffold. Tilorone, is an investigational antiviral agent that has shown a broad array of biological activities including cell growth inhibition in cancer cells, antifibrotic properties, α7 nicotinic receptor agonist activity, radioprotective activity and activation of hypoxia inducible factor-1. Quinacrine is an antimalarial but also has use as an anthelmintic. Our results suggest data sets with less than 1,000 molecules can produce validated machine learning models that can in turn be utilized to identify novel EBOV inhibitors in

  13. Effects of garlic and diallyl trisulfide on the growth, photosynthesis, and alkaline phosphatase activity of the toxic cyanobacterium Microcystis aeruginosa.

    Science.gov (United States)

    Wang, Shoubing; Wang, Yuanan; Ma, Xiaoxue; Xu, Ziran

    2016-03-01

    To identify a botanical algicide and elucidate the response of cyanobacteria to the extract from higher plants, the effects of garlic and garlic-derived diallyl trisulfide on Microcystis aeruginosa were studied. Effects were evaluated by changes in cell density, chlorophyll a, maximum effective quantum yield (Fv/Fm), effective quantum yield (YII), non-photochemical quenching (NPQ), and rapid light curves of M. aeruginosa. In addition, alkaline phosphatase activity (APA) was measured when M. aeruginosa was incubated with diallyl trisulfide. Results indicated that the inhibition by garlic and diallyl trisulfide was significant. The 120-h 50 % effective concentrations of garlic and diallyl trisulfide (EC50) were 0.75 g L(-1) and 2.84 mg L(-1), respectively. Moreover, the inhibitory rate increased with increasing concentration and the growth of M. aeruginosa was inhibited by 90.0 % at the highest concentrations. We also show that the response of M. aeruginosa to stress could involve both impairment of the photosynthetic center PSII and alteration of APA. For example, at high garlic concentration (2.0 g L(-1)), Fv/Fm significantly decreased from 0.501 to 0.084 (p garlic as an environmentally friendly algicide.

  14. Activation of Cyclic AMP Synthesis by Full and Partial Beta-Adrenergic Receptor Agonists in Chicken Skeletal Muscle Cells

    Science.gov (United States)

    Young, R. B.; Bridge, K. Y.

    2003-01-01

    Several beta-adrenergic receptor (bAR) agonists are known to cause hypertrophy of skeletal muscle tissue. Accordingly, five bAR agonists encompassing a range in activity from strong to weak were evaluated for their ability to stimulate CAMP accumulation in embryonic chicken skeletal muscle cells in culture. Two strong agonists (epinephrine and isoproterenol), one moderate agonist (albuterol), and two weak agonists known to cause hypertrophy in animals (clenbuterol and cimaterol) were studied. Dose response curves were determined over six orders of magnitude in concentration for each agonist, and values were determined for their maximum stimulation of CAMP synthesis rate (Bmax) and the agonist concentration at which 50% stimulation of CAMP synthesis (EC50) occurred. Bmax values decreased in the following order: isoproterenol, epinephrine, albuterol, cimaterol, clenbuterol. Cimaterol and clenbuterol at their Bmax concentrations were approximately 15-fold weaker than isoproterenol in stimulating the rate of CAMP synthesis. When cimaterol and clenbuterol were added to culture media at concentrations known to cause significant muscle hypertrophy in animals, there was no detectable effect on stimulation of CAMP synthesis. Finally, these same levels of cimaterol and clenbuterol did not antagonize the stimulation of CAMP by either epinephrine or isoproterenol.

  15. A New Negative Allosteric Modulator AP14145 for the Study of Small Conductance Calcium-Activated Potassium Channels

    DEFF Research Database (Denmark)

    Simo Vicens, Rafel; Kirchhoff, Jeppe Egedal; Dolce, Bernardo

    2017-01-01

    ) prolongation in anaesthetised rats and a beam walk test was performed in mice to determine acute CNS related effects of the drug. Key results: AP14145 was found to be an equipotent negative allosteric modulator of KCa2.2 and KCa2.3 channels (IC50 = 1.1 ± 0.3 μM L-1). The presence of AP14145 (10 μM L-1......) increased the EC50 of Ca2+ on KCa2.3 from 0.36 ± 0.02 μM L-1 to 1.2 ± 0.1 μM L-1. The inhibitory effect strongly depended on two amino acids, S508 and A533. AP14145 concentration-dependently prolonged AERP in rats. Moreover, AP14145 (10 mg kg-1) did not trigger any apparent CNS effects in mice. Conclusion...... and implications: AP14145 is a negative allosteric modulator of KCa2.2 and KCa2.3 that shifts the calcium dependence of channel activation, an effect strongly dependent on two identified amino acids. AP14145 prolongs AERP in rats and does not trigger any acute CNS effects in mice. The understanding of how KCa2...

  16. In vitro and in vivo antiparasitic activity of Azadirachtin against Argulus spp. in Carassius auratus (Linn. 1758).

    Science.gov (United States)

    Kumar, Saurav; Raman, R P; Kumar, Kundan; Pandey, P K; Kumar, Neeraj; Mohanty, Snatashree; Kumar, Abhay

    2012-05-01

    Argulus is one of the most common and predominant ectoparasites which cause serious parasitic disease and is a potent carrier of viruses and bacteria in the ornamental fish industry. In recent years, organic (herbs)-based medicines are widely used to cure the disease, and neem (Sarbaroganibarini) medicine is very popular and effective throughout the world. The present study was conducted to find the effects of Azadirachtin against Argulus spp. on Carassius auratus under in vitro and in vivo conditions. The 96-h median lethal concentration (LC(50)) for Azadirachtin EC 25% against Carassius auratus was found to be 82.115 mg L(-1). The antiparasitic activity test under in vitro and in vivo was evaluated at 1 (T1), 5 (T2), 10 (T3), 15 (T4) and 20 mg L(-1) (T5) to treat Argulus for 3 h and 72 h, respectively. In vitro effect of Azadirachtin solution led to 100% mortality of Argulus at 20 and 15 mg L(-1) for 2.5 and 3 h, respectively. Whereas, under in vivo test, the 100% antiparasitic efficacy of Azadirachtin solution was found at 15 and 20 mg L(-1) for 72 and 48 h, respectively. The EC(50) for 48 h was 20 mg L(-1), and thus, therapeutic index is 4.10. The results provided evidence that Azadirachtin can be used as a potential agent for controlling Argulus.

  17. Discovery of potential visfatin activators using in silico docking and ADME predictions as therapy for type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Olusola Olalekan Elekofehinti

    2018-06-01

    Full Text Available Visfatin (Nicotinamide phosphoribosyltransferase is an adipokine implicated in mediating insulin resistance and exhibiting insulin mimetic effect and therefore represents a druggable target for diabetes therapy. About 3,844 peroxisome proliferator activated receptor gamma (PPARγ agonists documented in Chembl database were docked with PPARγ and those with binding energy of >−9 kcal/mol having experimental EC50 of 0.1 to 1 nM were selected. The candidate compounds (27 were thereafter docked with visfatin (PDB ID: 4WQ6 using AutodockVina out of which eight compounds that ranked highest in binding energy (when compared with the co-crystallized ligand of visfatin: 3TQ were selected. Compound 25 exhibited favorable ligand-protein molecular interaction and respected Lipinski’s rule of five and interestingly from the absorption, distribution, metabolism and excretion (ADME-Toxicity analysis the compound have enhanced pharmacological properties than the current ligand of visfatin. Keywords: Nicotinamide phosphoribosyltransferase, Visfatin molecular docking, Type 2 diabetes, Adipokines

  18. Phenolic composition and free radical scavenging activity of different apple varieties in relation to the cultivar, tissue type and storage.

    Science.gov (United States)

    Carbone, K; Giannini, B; Picchi, V; Lo Scalzo, R; Cecchini, F

    2011-07-15

    The aim of this research was to evaluate the influence of genotype, tissue type and cold storage on the bioactive compounds content and on the antiradical activity (AA) of different apple cultivars (Golden cl. B, Fuji cl. Kiku8, Braeburn cl. Hillwell). The content of analysed phyto-compounds depended on the clone, on the part of fruit, and to a minor extent, on the storage. For EC(50) data, the cultivar represented the main source of variation and the interaction with the type of tissue, was significant. The AA of apples, measured by means of the DPPH test, was highly correlated to the flavan-3-ols content, which represents a good predictor of the apple antiradical power. The new Braeburn's clone, the Hillwell, had the worst AA related to a minor phyto-chemical content. Also, its phenolic content was dramatically reduced after cold storage (flesh: -50%; peels: -20%; papples, which is important to improve their quality and consumption benefits, suggesting to the breeders to pay more attention to the potential healthy compounds in the development of new hybrids. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Screening for Antibacterial and Antioxidant Activities and Phytochemical Analysis of Oroxylum indicum Fruit Extracts.

    Science.gov (United States)

    Sithisarn, Patchima; Nantateerapong, Petcharat; Rojsanga, Piyanuch; Sithisarn, Pongtip

    2016-04-07

    Oroxylum indicum, which is called Pheka in Thai, is a traditional Thai plant in the Bignoniaceae family with various ethnomedical uses such as as an astringent, an anti-inflammatory agent, an anti-bronchitic agent, an anti-helminthic agent and an anti-microbial agent. The young fruits of this plant have also been consumed as vegetables. However, there has been no report concerning its antibacterial activities, especially activities related to clinically isolated pathogenic bacteria and the in vitro antioxidant effects of this plant. Therefore, the extracts from O. indicum fruits and seeds collected from different provinces in Thailand were prepared by decoction and maceration with ethanol and determined for their in vitro antibacterial effects on two clinically isolated bacteria, Streptococcus suis and Staphylococcus intermedius, using disc diffusion assay. Ethanol extracts from O. indicum fruits collected from Nakorn Pathom province at the concentration of 1000 mg/mL exhibited intermediate antibacterial activity against S. intermedius with an inhibition zone of 15.11 mm. Moreover, it promoted moderate inhibitory effects on S. suis with an inhibition zone of 14.39 mm. The extracts prepared by maceration with ethanol promoted higher antibacterial activities than those prepared with water. The ethanol extract from the seeds of this plant, purchased in Bangkok, showed stronger in vitro antioxidant activities than the other extracts, with an EC50 value of 26.33 µg/mL. Phytochemical analysis suggested that the seed ethanol extract contained the highest total phenolic and flavonoid contents (10.66 g% gallic acid equivalent and 7.16 g% quercetin equivalent, respectively) by a significant amount. Thin layer chromatographic analysis of the extracts showed the chromatographic band that could correspond to a flavonoid baicalein. From the results, extracts from O. indicum fruits have an in vitro antioxidant effect, with antibacterial potential, on clinically pathologic

  20. Dasatinib inhibits both osteoclast activation and prostate cancer PC-3 cell-induced osteoclast formation

    Science.gov (United States)

    Araujo, John C.; Poblenz, Ann; Corn, Paul G.; Parikh, Nila U.; Starbuck, Michael W.; Thompson, Jerry T.; Lee, Francis; Logothetis, Christopher J.; Darnay, Bryant G.

    2013-01-01

    Purpose Therapies to target prostate cancer bone metastases have only limited effects. New treatments are focused on the interaction between cancer cells, bone marrow cells and the bone matrix. Osteoclasts play an important role in the development of bone tumors caused by prostate cancer. Since Src kinase has been shown to be necessary for osteoclast function, we hypothesized that dasatinib, a Src family kinase inhibitor, would reduce osteoclast activity and prostate cancer (PC-3) cell-induced osteoclast formation. Results Dasatinib inhibited RANKL-induced osteoclast differentiation of bone marrow-derived monocytes with an EC50 of 7.5 nM. PC-3 cells, a human prostate cancer cell line, were able to differentiate RAW 264.7 cells, a murine monocytic cell line, into osteoclasts and dasatinib inhibited this differentiation. In addition, conditioned medium from PC-3 cell cultures was able to differentiate RAW 264.7 cells into osteoclasts and this too, was inhibited by dasatinib. Even the lowest concentration of dasatinib, 1.25 nmol, inhibited osteoclast differentiation by 29%. Moreover, dasatinib inhibited osteoclast activity by 58% as measured by collagen 1 release. Experimental design We performed in vitro experiments utilizing the Src family kinase inhibitor dasatinib to target osteoclast activation as a means of inhibiting prostate cancer bone metastases. Conclusion Dasatinib inhibits osteoclast differentiation of mouse primary bone marrow-derived monocytes and PC-3 cell-induced osteoclast differentiation. Dasatinib also inhibits osteoclast degradation activity. Inhibiting osteoclast differentiation and activity may be an effective targeted therapy in patients with prostate cancer bone metastases. PMID:19855158

  1. Extraction method for high free radical scavenging activity of Siamese neem tree flowers

    Directory of Open Access Journals (Sweden)

    Worarat Chaisawangwong

    2009-10-01

    Full Text Available Siamese neem tree (Azadirachta indica A. Juss. var. siamensis Valeton is a medicinal plant found in Thailand. Youngleaves and young flowers of this plant are commonly consumed as a bitter tonic vegetable. The flowers are also used fortreatment of fever. The flower extract has been reported to exhibit in vitro free radical scavenging activity and can inhibitlipid peroxidation of bronchogenic cancer cell line. Active compounds in the flowers are flavonoids such as rutin andquercetin. The content of these compounds in the crude extract depends on the method of extraction. Therefore, the appropriateextraction method promoting high yield of total flavonoids and high free radical scavenging activity was investigated inthis study. Six different extraction methods, i.e. maceration, percolation, decoction, soxhlet extraction, ultrasonic extraction(UE, and microwave assisted extraction (MA were carried out for extracting dried powder of Siamese neem tree young flowers. The solvent used for maceration, percolation, and soxhlet extraction was 50% ethanol, while distilled water was used for decoction and MA, and both solvents were used for UE. The content of crude extract, free radical scavenging activity, and total flavonoids content of each extract were investigated and compared. Comparing the various extraction methods, decoction provided an extract containing a high amount of total flavonoids (17.54 mgRE/g extract and promoting the highest scavenging activity at EC50 11.36 g/ml. Decoction is also simple, cheap, and convenient and could be used in developing countries. Thus, it should be the recommended extraction method for the flowers of Siamese neem tree for furtherdevelopment of antioxidant pharmaceutical preparations.

  2. Phytochemicals Screening and Activities of Hydrophilic and Lipophilic Antioxidant of Some Fruit Peels

    International Nuclear Information System (INIS)

    Khairusy Syakirah Zulkifli; Noriham Abdullah; Aminah Abdullah; Nurain Aziman; Wan Saidatul Syida Wan Kamarudin

    2012-01-01

    This study was conducted to screen the secondary metabolites compounds including alkaloids, tannins, saponins and flavonoids as well as to determine the antioxidant activities of four types of fruit peels namely Psidium guajava (guava), Mangifera indica (Chakonan mango), Citrus sinensis (Navel orange) and Malus sylvestris (Granny Smith apple). The hydrophilic and lipophilic antioxidant activities were investigated using three different assays such as Ferric Reducing Antioxidant Power (FRAP), 2, 2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity and Oxygen Radical Absorbance Capacity (ORAC). Total Phenolic Content (TPC) and Total Flavonoids Content (TFC) were also conducted and the correlations between the antioxidant assays with TPC and TFC were evaluated. The TPC in the peels extract ranged between 204.90 to 517.00 mg GAE/ g extract weight while TFC ranged between 97.48 to 177.86 mg QE/ g extract weight. The FRAP, EC 50 scavenging activity and ORAC values were 18.78 to 45.36 mM TE/ 100 g extract weight, 0.146 to 0.717 mg/ ml scavenging effect and 37.54 to 60.59 μM TE/ g extract weight respectively. The extract of M. indica peels appeared to be as potent as ascorbic acid with maximum inhibition of 74 % at 200 ppm. M. indica peels showed highest value in all antioxidant assays and in TPC while the highest in TFC was found in M. sylvestris peels. There were strong correlations between all antioxidant assays with TPC but very weak correlations with TFC. This study suggested that the extracts of fruit peels are convenient to be use as functional ingredients in food product development as they are rich in antioxidant activities. (author)

  3. Antioxidant capacity and larvicidal activity of essential oil and extracts from Lippia grandis

    Directory of Open Access Journals (Sweden)

    Evelyn Ivana T. Damasceno

    2011-02-01

    Full Text Available The leaves and thin branches of Lippia grandis Schauer, Verbenaceae, are used for flavoring of food in the Brazilian Amazon, as substitute for oregano. In this study the constituents of the essential oil were identified and the antioxidant capacity and larvicidal activity of the oil and methanol extract and its sub-fractions were evaluated. A sensory evaluation was determined in view of absence of toxicity. The oil showed a yield of 2.1% and its main constituents were thymol (45.8%, p-cymene (14.3%, γ-terpinene (10.5%, carvacrol (9.9% and thymol methyl ether (4.8%, totalizing 85%. The DPPH radical scavenging activity showed values for the EC50 between 9.0 and 130.5 µg mL-1 and the TEAC/ABTS values varied from 131.1 to 336.0 mg TE/g, indicating significant antioxidant activity for the plant. The total phenolic content ranged from 223.0 to 761.4 mg GAE/g, contributing to the antioxidant activity observed. The crude extracts inhibited the bleaching of β-carotene and the oil showed the greatest inhibition (42.5%. The oil (LgO, 7.6±2.4 µg mL-1 showed strong larvicidal activity against the brine shrimp bioassay. The sensory evaluation was highly satisfactory in comparison to oregano. The results are very promising for the use of L. grandis in seasoning and antioxidant products.

  4. Rapid Screening of Active Components with an Osteoclastic Inhibitory Effect in Herba epimedii Using Quantitative Pattern–Activity Relationships Based on Joint-Action Models

    Directory of Open Access Journals (Sweden)

    Xiao-Yan Yuan

    2017-10-01

    Full Text Available Screening of bioactive components is important for modernization and quality control of herbal medicines, while the traditional bioassay-guided phytochemical approach is time-consuming and laborious. The presented study proposes a strategy for rapid screening of active components from herbal medicines. As a case study, the quantitative pattern–activity relationship (QPAR between compounds and the osteoclastic inhibitory effect of Herba epimedii, a widely used herbal medicine in China, were investigated based on joint models. For model construction, standard mixtures data showed that the joint-action models are better than the partial least-squares (PLS model. Then, the Good2bad value, which could reflect components’ importance based on Monte Carlo sampling, was coupled with the joint-action models for screening of active components. A compound (baohuoside I and a component composed of compounds with retention times in the 6.9–7.9 min range were selected by our method. Their inhibition rates were higher than icariin, the key bioactive compound in Herba epimedii, which could inhibit osteoclast differentiation and bone resorption in a previous study. Meanwhile, the half-maximal effective concentration, namely, EC50 value of the selected component was 7.54 μg/mL, much smaller than that of baohuoside I—77 μg/mL—which indicated that there is synergistic action between compounds in the selected component. The results clearly show our proposed method is simple and effective in screening the most-bioactive components and compounds, as well as drug-lead components, from herbal medicines.

  5. Investigation of the acaricidal activity of the acetone and ethanol extracts of 12 South African plants against the adult ticks of Rhipicephalus turanicus

    Directory of Open Access Journals (Sweden)

    Gerda Fouche

    2017-11-01

    Full Text Available The acaricidal activity of acetone and ethanol extracts of 12 plant species was evaluated using the contact method on Rhipicephalus turanicus (Acari: Ixodidae ticks at an initial concentration of 20% (200 mg/mL. Eight of the 12 plants had mortality greater than 50% and the acetone extracts had better acaricidal activity than the ethanol extracts. The acetone extract of Calpurnia aurea (leaves and flowers had the highest corrected mortality (CM of 92.2% followed by Schkuhria pinnata (whole plant with a CM of 88.9%, Ficus sycomorus (bark and stems 86.7% and Senna italica subsp. arachoides (roots, leaves and fruits 83.3%. Selected extracts were tested at five different concentrations using the adult immersion test. From dose–response assays, EC50 values of 61.82 mg/mL, 115.21 mg/mL and 161.02 mg/mL were obtained for the acetone extracts of S. pinnata (whole plant, S. italica subsp. arachoides (roots, leaves and fruits and C. aurea (leaves and flowers respectively. The ethanol extract of Monsonia angustifolia (whole plant had the highest CM of 97.8% followed by S. pinnata (whole plant with a CM of 86.7%, C. aurea (leaves and flowers 81.1% and Cleome gynandra (leaves 77.8%. There is potential for the development of environmentally benign botanicals as natural acaricides against R. turanicus.

  6. Linear and non-linear quantitative structure-activity relationship models on indole substitution patterns as inhibitors of HIV-1 attachment.

    Science.gov (United States)

    Nirouei, Mahyar; Ghasemi, Ghasem; Abdolmaleki, Parviz; Tavakoli, Abdolreza; Shariati, Shahab

    2012-06-01

    The antiviral drugs that inhibit human immunodeficiency virus (HIV) entry to the target cells are already in different phases of clinical trials. They prevent viral entry and have a highly specific mechanism of action with a low toxicity profile. Few QSAR studies have been performed on this group of inhibitors. This study was performed to develop a quantitative structure-activity relationship (QSAR) model of the biological activity of indole glyoxamide derivatives as inhibitors of the interaction between HIV glycoprotein gp120 and host cell CD4 receptors. Forty different indole glyoxamide derivatives were selected as a sample set and geometrically optimized using Gaussian 98W. Different combinations of multiple linear regression (MLR), genetic algorithms (GA) and artificial neural networks (ANN) were then utilized to construct the QSAR models. These models were also utilized to select the most efficient subsets of descriptors in a cross-validation procedure for non-linear log (1/EC50) prediction. The results that were obtained using GA-ANN were compared with MLR-MLR and MLR-ANN models. A high predictive ability was observed for the MLR, MLR-ANN and GA-ANN models, with root mean sum square errors (RMSE) of 0.99, 0.91 and 0.67, respectively (N = 40). In summary, machine learning methods were highly effective in designing QSAR models when compared to statistical method.

  7. Delta(9)-tetrahydrocannabinol inhibits 17beta-estradiol-induced proliferation and fails to activate androgen and estrogen receptors in MCF7 human breast cancer cells.

    Science.gov (United States)

    von Bueren, A O; Schlumpf, M; Lichtensteiger, W

    2008-01-01

    Delta(9)-tetrahydrocannabinol (THC) exerts palliative effects in cancer patients, but produces adverse effects on the endocrine and reproductive systems. Experimental evidence concerning such effects is controversial. Whether THC exhibits estrogenic or androgenic activity in vitro was investigated. Estrogenic effects of THC were analyzed in vitro by measuring the proliferation of estrogen-sensitive MCF7 cells. Androgenic activity was investigated by the A-Screen assay that measures androgen-dependent inhibition of proliferation of the androgen receptor (AR)-positive human mammary carcinoma cell line, MCF7-AR1. In contrast to 17beta-estradiol, included as positive control with an EC50 value (concentration required for 50% of maximal 17beta-estradiol-induced proliferation) of 1.00 x 10(-12) M, THC failed to induce cell proliferation in the MCF7 cell line at concentrations between 10(-13) and 10(-4) M. THC inhibited 17beta-estradiol-induced proliferation in wild-type MCF7 and MCF7-AR1 cells, with an IC50 value of 2.6 x 10(-5) M and 9 x 10(-6) M, respectively. THC failed to act as an estrogen, but antagonized 17beta-estradiol-induced proliferation. This effect was independent of the AR expression level.

  8. Ultrasonic-assisted enzymatic extraction of phenolics from broccoli (Brassica oleracea L. var. italica) inflorescences and evaluation of antioxidant activity in vitro.

    Science.gov (United States)

    Wu, Hao; Zhu, Junxiang; Yang, Long; Wang, Ran; Wang, Chengrong

    2015-06-01

    An efficient ultrasonic-assisted enzymatic extraction technique was applied to extracting phenolics from broccoli inflorescences without organic solvents. The synergistic model of enzymolysis and ultrasonication simultaneously was selected, and the enzyme combination was optimized by orthogonal test: cellulase 7.5 mg/g FW (fresh weight), pectinase 10 mg/g FW, and papain 1.0 mg/g FW. The operating parameters in ultrasonic-assisted enzymatic extraction were optimized with response surface methodology using Box-Behnken design. The optimal extraction conditions were as follows: ultrasonic power, 440 W; liquid to material ratio, 7.0:1 mL/g; pH value of 6.0 at 54.5 ℃ for 10 min. Under these conditions, the extraction yield of phenolics achieved 1.816 ± 0.0187 mg gallic acid equivalents/gram FW. The free radical scavenging activity of ultrasonic-assisted enzymatic extraction extracts was determined by 1,1-diphenyl-2-picrylhydrazyl·assay with EC50 values of 0.25, and total antioxidant activity was determined by ferric reducing antioxidant power assay with ferric reducing antioxidant power value of 0.998 mmol FeSO4/g compared with the referential ascorbic acid of 1.184 mmol FeSO4/g. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  9. Synthesis and Fungicidal Activities of (Z/E-3,7-Dimethyl-2,6-octadienamide and Its 6,7-Epoxy Analogues

    Directory of Open Access Journals (Sweden)

    Mingyan Yang

    2015-11-01

    Full Text Available In order to find new lead compounds with high fungicidal activity, (Z/E-3,7-dimethyl-2,6-octadienoic acids were synthesized via selective two-step oxidation using the commercially available geraniol/nerol as raw materials. Twenty-eight different (Z/E-3,7-dimethyl-2,6-octadienamide derivatives were prepared by reactions of (Z/E-carboxylic acid with various aromatic and aliphatic amines, followed by oxidation of peroxyacetic acid to afford their 6,7-epoxy analogues. All of the compounds were characterized by HR-ESI-MS and 1H-NMR spectral data. The preliminary bioassays showed that some of these compounds exhibited good fungicidal activities against Rhizoctonia solani (R. solani at a concentration of 50 µg/mL. For example, 5C, 5I and 6b had 94.0%, 93.4% and 91.5% inhibition rates against R. solani, respectively. Compound 5f displayed EC50 values of 4.3 and 9.7 µM against Fusahum graminearum and R. Solani, respectively.

  10. Synthesis and Structure-Activity Relationships of N-Dihydrocoptisine-8-ylidene Aromatic Amines and N-Dihydrocoptisine-8-ylidene Aliphatic Amides as Antiulcerative Colitis Agents Targeting XBP1.

    Science.gov (United States)

    Xie, Meng; Zhang, Hai-Jing; Deng, An-Jun; Wu, Lian-Qiu; Zhang, Zhi-Hui; Li, Zhi-Hong; Wang, Wen-Jie; Qin, Hai-Lin

    2016-04-22

    In this study, natural quaternary coptisine was used as a lead compound to design and synthesize structurally stable and actively potent coptisine analogues. Of the synthesized library, 13 N-dihydrocoptisine-8-ylidene amines/amides were found not only to be noncytotoxic toward intestinal epithelial cells (IECs), but they were also able to activate the transcription of X-box-binding protein 1 (XBP1) targets to varying extents in vitro. Antiulcerative colitis (UC) activity levels were assessed at the in vitro molecular level as well as in vivo in animals using multiple biomarkers as indices. In an in vitro XBP1 transcriptional activity assay, four compounds demonstrated good dose-effect relationships with EC50 values of 0.0708-0.0132 μM. Moreover, two compounds were confirmed to be more potent in vivo than a positive control, demonstrating a curative effect for UC in experimental animals. Thus, the findings of this study suggest that these coptisine analogues are promising candidates for the development of anti-UC drugs.

  11. Effects of cocaine on norepinephrine stimulated phosphoinositide hydrolysis and locomotor activity in rat

    International Nuclear Information System (INIS)

    Mosaddeghi, M.

    1989-01-01

    The function of α 1 -adrenoceptors was determined by stimulating cortical tissue slices, which were pre-labeled with [ 3 H]inositol, with norepinephrine (NE) in the presence of 8 mM LiCl. Results of in vitro studies showed that cocaine 10 μM potentiated maximal NE-stimulated PI hydrolysis by 30%. In addition, the EC 50 was decreased from 3.93 ± 0.42 to 1.91 ± 0.31 μM NE. Concentrations of 0.1-100 μM and 0.1-10 μM cocaine enhanced PI hydrolysis stimulated by 0.3 and 3 μM NE, respectively. The concentration-effect curves for NE-stimulated PI hydrolysis were shifted to the right 100-fold in the presence of 0.1 μM prazosin. Cocaine (10 μM) did not potentiate NE-stimulated PI hydrolysis in the presence of 0.1 μM prazosin. [ 3 H]Prazosin saturation and NE [ 3 H]prazosin competition binding studies using crude membrane preparations showed that 10 μM cocaine did not alter binding parameters B max , K d , Hill slope, and IC 50 . Together, these results implied that cocaine in vitro potentiated NE-stimulated PI hydrolysis by blocking NE reuptake. For in vivo studies, the locomotor activity was determined after an acute or chronic injections of either cocaine or saline. Cocaine or saline-treated rats were killed after measurement of the locomotor activity, and NE-stimulated PI hydrolysis was measured. Acute administration of cocaine 3.2-42 mg/kg (i.p.) produced an inverted U shaped dose-response curve on locomotor activity. The peak increase in locomotor activity was at 32 mg/kg cocaine. A dose of 42 mg/kg cocaine produced a significant depression of maximal NE-stimulated PI hydrolysis

  12. Anti-BACE1 and Antimicrobial Activities of Steroidal Compounds Isolated from Marine Urechis unicinctus

    Directory of Open Access Journals (Sweden)

    Yong-Zhe Zhu

    2018-03-01

    Full Text Available The human β-site amyloid cleaving enzyme (BACE1 has been considered as an effective drug target for treatment of Alzheimer’s disease (AD. In this study, Urechis unicinctus (U. unicinctus, which is a Far East specialty food known as innkeeper worm, ethanol extract was studied by bioassay-directed fractionation and isolation to examine its potential β-site amyloid cleaving enzyme inhibitory and antimicrobial activity. The following compounds were characterized: hecogenin, cholest-4-en-3-one, cholesta-4,6-dien-3-ol, and hurgadacin. These compounds were identified by their mass spectrometry, 1H, and 13C NMR spectral data, comparing those data with NIST/EPA/NIH Mass spectral database (NIST11 and published values. Hecogenin and cholest-4-en-3-one showed significant inhibitory activity against BACE1 with EC50 values of 116.3 and 390.6 µM, respectively. Cholesta-4,6-dien-3-ol and hurgadacin showed broad spectrum antimicrobial activity, particularly strongly against Escherichia coli (E. coli, Salmonella enterica (S. enterica, Pasteurella multocida (P. multocida, and Physalospora piricola (P. piricola, with minimal inhibitory concentration (MIC ranging from 0.46 to 0.94 mg/mL. This is the first report regarding those four known compounds that were isolated from U. unicinctus and their anti-BACE1 and antimicrobial activity, highlighting the fact that known natural compounds may be a critical source of new medicine leads. These findings provide scientific evidence for potential application of those bioactive compounds for the development of AD drugs and antimicrobial agents.

  13. Anti-BACE1 and Antimicrobial Activities of Steroidal Compounds Isolated from Marine Urechis unicinctus.

    Science.gov (United States)

    Zhu, Yong-Zhe; Liu, Jing-Wen; Wang, Xue; Jeong, In-Hong; Ahn, Young-Joon; Zhang, Chuan-Jie

    2018-03-14

    The human β-site amyloid cleaving enzyme (BACE1) has been considered as an effective drug target for treatment of Alzheimer's disease (AD). In this study, Urechis unicinctus (U. unicinctus) , which is a Far East specialty food known as innkeeper worm, ethanol extract was studied by bioassay-directed fractionation and isolation to examine its potential β-site amyloid cleaving enzyme inhibitory and antimicrobial activity. The following compounds were characterized: hecogenin, cholest-4- en -3-one, cholesta-4,6- dien -3-ol, and hurgadacin. These compounds were identified by their mass spectrometry, ¹H, and 13 C NMR spectral data, comparing those data with NIST/EPA/NIH Mass spectral database (NIST11) and published values. Hecogenin and cholest-4- en -3-one showed significant inhibitory activity against BACE1 with EC 50 values of 116.3 and 390.6 µM, respectively. Cholesta-4,6- dien -3-ol and hurgadacin showed broad spectrum antimicrobial activity, particularly strongly against Escherichia coli (E. coli) , Salmonella enterica (S. enterica) , Pasteurella multocida (P. multocida) , and Physalospora piricola (P. piricola) , with minimal inhibitory concentration (MIC) ranging from 0.46 to 0.94 mg/mL. This is the first report regarding those four known compounds that were isolated from U. unicinctus and their anti-BACE1 and antimicrobial activity, highlighting the fact that known natural compounds may be a critical source of new medicine leads. These findings provide scientific evidence for potential application of those bioactive compounds for the development of AD drugs and antimicrobial agents.

  14. Organotins Are Potent Activators of PPARγ and Adipocyte Differentiation in Bone Marrow Multipotent Mesenchymal Stromal Cells

    Science.gov (United States)

    Yanik, Susan C.; Baker, Amelia H.; Mann, Koren K.; Schlezinger, Jennifer J.

    2011-01-01

    Adipocyte differentiation in bone marrow is potentially deleterious to both bone integrity and lymphopoiesis. Here, we examine the hypothesis that organotins, common environmental contaminants that are dual ligands for peroxisome proliferator–activated receptor (PPAR) γ and its heterodimerization partner retinoid X receptor (RXR), are potent activators of bone marrow adipogenesis. A C57Bl/6-derived bone marrow multipotent mesenchymal stromal cell (MSC) line, BMS2, was treated with rosiglitazone, a PPARγ agonist, bexarotene, an RXR agonist, or a series of organotins. Rosiglitazone and bexarotene potently activated adipocyte differentiation; however, bexarotene had a maximal efficacy of only 20% of that induced by rosiglitazone. Organotins (tributyltin [TBT], triphenyltin, and dibutyltin) also stimulated adipocyte differentiation (EC50 of 10–20nM) but with submaximal, structure-dependent efficacy. In coexposures, both bexarotene and TBT enhanced rosiglitazone-induced adipogenesis. To investigate the contribution of PPARγ to TBT-induced adipogenesis, we examined expression of PPARγ2, as well as its transcriptional target FABP4. TBT-induced PPARγ2 and FABP4 protein expression with an efficacy intermediate between rosiglitazone and bexarotene, similar to lipid accumulation. A PPARγ antagonist and PPARγ-specific small hairpin RNA suppressed TBT-induced differentiation, although to a lesser extent than rosiglitazone-induced differentiation, suggesting that TBT may engage alternate pathways. TBT and bexarotene, but not rosiglitazone, also induced the expression of TGM2 (an RXR target) and ABCA1 (a liver X receptor target). The results show that an environmental contaminant, acting with the same potency as a therapeutic drug, induces PPARγ-dependent adipocyte differentiation in bone marrow MSCs. Activation of multiple nuclear receptor pathways by organotins may have significant implications for bone physiology. PMID:21622945

  15. Antioxidant and Antimicrobial Activities of 7-Hydroxy-calamenene-Rich Essential Oils from Croton cajucara Benth.

    Directory of Open Access Journals (Sweden)

    Celuta S. Alviano

    2013-01-01

    Full Text Available Croton cajucara is a shrub native to the Amazon region locally known as “sacaca”. Two morphotypes are known: white and red “sacaca”. The essential oils (EO obtained by hydrodistillation from leaves of the red morphotype were, in general, rich in 7-hydroxycalamenene (28.4%–37.5%. The effectiveness of these EO regarding the antimicrobial activity against pathogenic microorganisms was initially investigated by the drop test method, showing significant inhibition zones. Among the microorganisms tested, the essential oils rich in 7-hydroxycalamenene were more effective against methicillin resistant Staphylococcus aureus (MRSA, Enterococcus faecalis, Mycobacterium tuberculosis, M. smegmatis, Mucor circinelloides and Rhizopus oryzae. The minimum inhibitory concentrations (MIC of the oils were determined using the broth dilution assay. It was possible to observe that 7-hydroxycalamenene-rich oils presented high antimicrobial activity, with MIC of 4.76 × 10−3 μg/mL for MRSA, 4.88 μg/mL for M. tuberculosis, 39.06 μg/mL for M. smegmatis, and 0.152 μg/mL for R. oryzae and 3.63 × 10−8 μg/mL for M. circinelloides. The antioxidant activity of this EO suggests that 7-hydroxycalamenene provides more antioxidant activity according with EC50 less than 63.59 μg/mL. Considering the bioactive potential of EOs and 7-hydroxycalamenene could be of great interest for development of antimicrobials for therapeutic use in treatment of bacterial and fungal infections in humans and/or veterinary practice.

  16. Antioxidant, antimutagenic and antiproliferative activities in selected seaweed species from Sinaloa, Mexico.

    Science.gov (United States)

    Osuna-Ruiz, Idalia; López-Saiz, Carmen-María; Burgos-Hernández, Armando; Velázquez, Carlos; Nieves-Soto, Mario; Hurtado-Oliva, Miguel A

    2016-10-01

    Context Seaweeds from the Mexican Pacific Ocean have not been evaluated as a source of chemoprotectants. Objective The objective of this study is to evaluate chemopreventive activities of the seaweeds Phaephyceae - Padina durvillaei (Dictyotaceae) - Rodhophyceae - Spyridia filamentosa (Spyridiaceae), Gracilaria vermiculophylla (Gracilariaceae) - and Chlorophyceae - Ulva expansa (Ulvaceae), Codium isabelae (Codiaceae), Rhizoclonium riparium (Cladophoraceae) and Caulerpa sertularioides (Caulerpaceae). Materials and methods Methanol, acetone and hexane seaweed extracts were assessed at 30 and 3 mg/mL on antioxidant capacity (DPPH and ABTS assays), 0.003-3.0 mg/plate on antimutagenic activity against AFB1 using Salmonella typhimurium TA98 and TA100 tester strains in Ames test, and 12.5 to 100 μg/mL on antiproliferative activity on Murine B-cell lymphoma. Phenols, flavonoids and pigments content were also assessed as antioxidant compounds. Results Extraction yield was higher in methanol than in acetone and hexane extracts (6.4, 2.7 and 1.4% dw). Antioxidant capacity was higher in brown and green than in red seaweed species, particularly in P. durvillaei extracted in acetone (EC50  value= 16.9 and 1.56 mg/mL for DPPH and ABTS). Flavonoids and chlorophylls were identified as mainly antioxidant components; particularly in hexane extracts, which were correlated with the antioxidant capacity. Highest mutagenesis inhibition (> 40%) occurred in R. riparium at the lowest concentration assayed (0.003 mg/plate), while highest antiproliferative inhibition (37 and 72% for 12.5 and 25 μg/mL) occurred in C. sertularioides. Discussion and conclusion Flavonoids and chlorophylls explained the chemopreventive activities assessed in S. filamentosa, R. riparium and C. sertularioides. These seaweeds have a high potential as a source of novel chemoprotectants.

  17. Nematicidal Activity of Kojic Acid Produced by Aspergillus oryzae against Meloidogyne incognita.

    Science.gov (United States)

    Kim, Tae Yoon; Jang, Ja Yeong; Jeon, Sun Jeong; Lee, Hye Won; Bae, Chang-Hwan; Yeo, Joo Hong; Lee, Hyang Burm; Kim, In Seon; Park, Hae Woong; Kim, Jin-Cheol

    2016-08-28

    The fungal strain EML-DML3PNa1 isolated from leaf of white dogwood (Cornus alba L.) showed strong nematicidal activity with juvenile mortality of 87.6% at a concentration of 20% fermentation broth filtrate at 3 days after treatment. The active fungal strain was identified as Aspergillus oryzae, which belongs to section Flavi, based on the morphological characteristics and sequence analysis of the ITS rDNA, calmodulin (CaM), and β-tubulin (BenA) genes. The strain reduced the pH value to 5.62 after 7 days of incubation. Organic acid analysis revealed the presence of citric acid (515.0 mg/kg), malic acid (506.6 mg/kg), and fumaric acid (21.7 mg/kg). The three organic acids showed moderate nematicidal activities, but the mixture of citric acid, malic acid, and fumaric acid did not exhibit the full nematicidal activity of the culture filtrate of EML- DML3PNa1. Bioassay-guided fractionation coupled with (1)H- and (13)C-NMR and EI-MS analyses led to identification of kojic acid as the major nematicidal metabolite. Kojic acid exhibited dose-dependent mortality and inhibited the hatchability of M. incognita, showing EC50 values of 195.2 µg/ml and 238.3 µg/ml, respectively, at 72 h postexposure. These results suggest that A. oryzae EML-DML3PNa1 and kojic acid have potential as a biological control agent against M. incognita.

  18. Inhibitory effect on nitric oxide production and free radical scavenging activity of Thai medicinal plants in osteoarthritic knee treatment.

    Science.gov (United States)

    Anuthakoengkun, Areeya; Itharat, Arunporn

    2014-08-01

    Thai medicine plants used for Osteoarthritis of knee (OA) treatment consist of twelve plants such as Crinumn asiaticum, Cleome viscosa, Drypetes roxburghii, Piper longum, Piper nigrum, Plumbago indica, Alpinia galanga, Curcuma aromatica, Globba malaccensis, Zingiber montanum, Zingiber officinale andZingiberzerumbet. They showedhighfrequency in OA formula. To investigate inhibitory effect on LPS-induced nitric oxide (NO) release from RAW264. 7 cell and free radical scavenging activity usingDPPH assay of these ethanolic plant extracts. Plant materials were extracted by maceration in 95% ethanol. Anti-inflammatory activity were tested on LPS-induced NO production. Free radical scavenging activity was performed by DPPH assay. All of ethanolic extracts exhibited potent inhibitory effect on NO release. The ethanolic extract of Z. zerumbet exhibited the highest inhibitory effect followed by Z. montanum and G. malaccensis, respectively. Except A. galanga and C. viscosa, all extracts possessed more influential than indomethacin (IC50 = 20.32±3.23 μLg/ml), a positive control. The investigation on antioxidant activity suggested that the ethanolic extracts of D. roxburghii, Z. officinale, Z. montanum, C. aromatic, A. galanga, P indica, G malaccensis, P nigrum exhibited antioxidant activity. By means ofD. roxburghii had the highest electron donating activity,followed by Z. officinale. Moreover both extracts were more effective than BHT apositive control (EC50 = 14.04±1.95 μg/ml). Thai medicinal plants had anti-inflammatory activity and could inhibit destruction of articular cartilage that corresponded to the traditional medicine and supported using these medicinal plants for OA treatment.

  19. Ginseng gintonin activates the human cardiac delayed rectifier K+ channel: involvement of Ca2+/calmodulin binding sites.

    Science.gov (United States)

    Choi, Sun-Hye; Lee, Byung-Hwan; Kim, Hyeon-Joong; Jung, Seok-Won; Kim, Hyun-Sook; Shin, Ho-Chul; Lee, Jun-Hee; Kim, Hyoung-Chun; Rhim, Hyewhon; Hwang, Sung-Hee; Ha, Tal Soo; Kim, Hyun-Ji; Cho, Hana; Nah, Seung-Yeol

    2014-09-01

    Gintonin, a novel, ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, elicits [Ca(2+)]i transients in neuronal and non-neuronal cells via pertussis toxin-sensitive and pertussis toxin-insensitive G proteins. The slowly activating delayed rectifier K(+) (I(Ks)) channel is a cardiac K(+) channel composed of KCNQ1 and KCNE1 subunits. The C terminus of the KCNQ1 channel protein has two calmodulin-binding sites that are involved in regulating I(Ks) channels. In this study, we investigated the molecular mechanisms of gintonin-mediated activation of human I(Ks) channel activity by expressing human I(Ks) channels in Xenopus oocytes. We found that gintonin enhances IKs channel currents in concentration- and voltage-dependent manners. The EC50 for the I(Ks) channel was 0.05 ± 0.01 μg/ml. Gintonin-mediated activation of the I(Ks) channels was blocked by an LPA1/3 receptor antagonist, an active phospholipase C inhibitor, an IP3 receptor antagonist, and the calcium chelator BAPTA. Gintonin-mediated activation of both the I(Ks) channel was also blocked by the calmodulin (CaM) blocker calmidazolium. Mutations in the KCNQ1 [Ca(2+)]i/CaM-binding IQ motif sites (S373P, W392R, or R539W)blocked the action of gintonin on I(Ks) channel. However, gintonin had no effect on hERG K(+) channel activity. These results show that gintonin-mediated enhancement of I(Ks) channel currents is achieved through binding of the [Ca(2+)]i/CaM complex to the C terminus of KCNQ1 subunit.

  20. AKTIVITAS ANTIOKSIDAN EKSTRAK UMBI AKAR GINSENG JAWA (Talinum triangulare Willd. [Antioxidant Activity of Javanese Ginseng (Talinum triangulare Willd. Root Extracts

    Directory of Open Access Journals (Sweden)

    Teti Estiasih1

    2006-12-01

    Full Text Available Antioxidant activity of some extracts of javanese ginseng root was investigated. Javanese ginseng root extracts were prepared by solvent extraction using methanol, ethanol (96%, ethanol (70%, acetone, and hexane. Total antioxidant activity of the extracts was measured by ferric thiocyanate method, whereas radical scavenging capacity and reducing power were measured by the 1,1-diphenyl-2-picrylhydrazyl and the reducing potential methods, respectively. The result showed that the highest total antioxidant activity was observed in acetone and methanol extracts. It was supposed that the ability of these extracts for partitioning at the interface of the emulsion in the tested oxidation system was the highest among other extracts, therefore it had the best activity to inhibit oxidation. The highest radical scavenging capacity measured by EC50 was observed in acetone extract. The type of phenolic compounds of this extract was suggested to be responsible for the highest radical scavenging capacity. Different phenomena occurred for reducing power. Methanol extract had the highest reducing power and the least is hexane and acetone extract. It was suggested that each extracts comprised different types of phenolic based on different polarity of solvents used for extraction. The antioxidant compounds of javanese ginseng root extracts were primary antioxidant based on these ability to scavenge free radical. It could be concluded that acetone was the best solvent for antioxidant extraction of javanese ginseng root. However, all tested antioxidant mechanisms in this research showed that vitamin E (1000 ppm had better activity than javanese ginseng root extracts (1000 ppm for all types of solvent. Javanese ginseng extracts might contain other compounds that not responsible for antioxidant activity, therefore at the same concentration the activity were lower than vitamin E.

  1. Antidiarrheal Activity of Aqueous Extract of the Stem Bark of Sapium ...

    African Journals Online (AJOL)

    AESE, in a concentration-dependent manner, reduced the tone and amplitude of spontaneous contractions of the ileal smooth muscle with EC50 of 33.29 and 45.43 μg/ml, respectively. None of the doses used in acute toxicity test induced any significant behavioral changes or mortality. Conclusion: These results suggest ...

  2. Transcriptional profiling of the dose response: a more powerful approach for characterizing drug activities.

    Directory of Open Access Journals (Sweden)

    Rui-Ru Ji

    2009-09-01

    Full Text Available The dose response curve is the gold standard for measuring the effect of a drug treatment, but is rarely used in genomic scale transcriptional profiling due to perceived obstacles of cost and analysis. One barrier to examining transcriptional dose responses is that existing methods for microarray data analysis can identify patterns, but provide no quantitative pharmacological information. We developed analytical methods that identify transcripts responsive to dose, calculate classical pharmacological parameters such as the EC50, and enable an in-depth analysis of coordinated dose-dependent treatment effects. The approach was applied to a transcriptional profiling study that evaluated four kinase inhibitors (imatinib, nilotinib, dasatinib and PD0325901 across a six-logarithm dose range, using 12 arrays per compound. The transcript responses proved a powerful means to characterize and compare the compounds: the distribution of EC50 values for the transcriptome was linked to specific targets, dose-dependent effects on cellular processes were identified using automated pathway analysis, and a connection was seen between EC50s in standard cellular assays and transcriptional EC50s. Our approach greatly enriches the information that can be obtained from standard transcriptional profiling technology. Moreover, these methods are automated, robust to non-optimized assays, and could be applied to other sources of quantitative data.

  3. A novel M1 PAM VU0486846 exerts efficacy in cognition models without displaying agonist activity or cholinergic toxicity.

    Science.gov (United States)

    Rook, Jerri M; Bertron, Jeanette L; Cho, Hyekyung P; Garcia-Barrantes, Pedro M; Moran, Sean P; Maksymetz, James T; Nance, Kellie D; Dickerson, Jonathan W; Remke, Daniel H; Chang, Sichen; Harp, Joel; Blobaum, Anna L; Niswender, Colleen M; Jones, Carrie K; Stauffer, Shaun R; Conn, P Jeffrey; Lindsley, Craig W

    2018-04-27

    Selective activation of the M1 subtype of muscarinic acetylcholine receptor, via positive allosteric modulation (PAM), is an exciting strategy to improve cognition in schizophrenia and Alzheimer's disease patients. However, highly potent M1 ago-PAMs, such as MK-7622, PF-06764427, and PF-06827443, can engender excessive activation of M1, leading to agonist actions in the prefrontal cortex (PFC) that impairs cognitive function, induces behavioral convulsions, and results in other classic cholinergic adverse events (AEs). Here, we report a fundamentally new and highly selective M1 PAM, VU0486846. VU0486846 possesses only weak agonist activity in M1-expressing cell lines with high receptor reserve and is devoid of agonist actions in the PFC, unlike previously reported ago-PAMs MK-7622, PF-06764427 and PF-06827443. Moreover, VU0486846 shows no interaction with antagonist binding at the orthosteric acetylcholine (ACh) site (e.g., neither bitopic nor displaying negative cooperativity with [3H]-NMS binding at theorthosteric site), no seizure liability at high brain exposures, and no cholinergic AEs. However, as opposed to ago-PAMs, VU0486846 produces robust efficacy in the novel object recognition model of cognitive function. Importantly, we show for the first time that an M1 PAM can reverse the cognitive deficits induced by atypical antipsychotics, such as risperidone. These findings further strengthen the argument that compounds with modest in vitro M1 PAM activity (EC50s > 100 nM) and pure-PAM activity in native tissues display robust pro-cognitive efficacy without AEs mediated by excessive activation of M1. Overall, the combination of compound assessment with recombinant in vitro assays (mindful of receptor reserve), native tissue systems (PFC), and phenotypic screens (behavioral convulsions) is essential to fully understand and evaluate lead compounds and enhance success in clinical development.

  4. Comparative antihemolytic and radical scavenging activities of strawberry tree (Arbutus unedo L.) leaf and fruit.

    Science.gov (United States)

    Mendes, Lídia; de Freitas, Victor; Baptista, Paula; Carvalho, Márcia

    2011-09-01

    The present study reports the antioxidant properties of Arbutus unedo L. leaf and fruit extracts using different in vitro assays including (i) reducing power, (ii) scavenging effect on DPPH free radicals, and (iii) inhibitory effect on AAPH-induced hemolysis and lipid peroxidation in human erythrocytes. All assays demonstrated antioxidant efficiency for A. unedo L. aqueous extracts, being consistently higher in the leaf. EC(50) values for reducing power and DPPH radical scavenging activities were, respectively, 0.318 ± 0.007 and 0.087 ± 0.007 mg/mL for leaf, and 2.894 ± 0.049 and 0.790 ± 0.016 mg/mL for fruit extracts. Under the oxidative action of AAPH, A. unedo leaf and fruit extracts protected the erythrocyte membrane from hemolysis (IC(50) of 0.062 ± 0.002 and 0.430 ± 0.091 mg/mL, respectively) and decreased the levels of malondialdehyde, a breakdown product of lipid peroxidation (IC(50) of 0.075 ± 0.014 and 0.732 ± 0.452 mg/mL, respectively). In accordance with antioxidant activity, phenolic content was found to be significantly higher in leaf extract. To our knowledge, this is the first time that the antioxidant activity of A. unedo species is evaluated using human biological membranes. Overall, our results suggest that A. unedo leaves are a promising source of natural antioxidants with potential application in diseases mediated by free radicals. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Phototransformation of sulfamethoxazole under simulated sunlight: Transformation products and their antibacterial activity toward Vibrio fischeri

    International Nuclear Information System (INIS)

    Gmurek, M.; Horn, H.; Majewsky, M.

    2015-01-01

    Sulfamethoxazole (SMX) is a bacteriostatic antibiotic ubiquitously found in the aquatic environment. Since conventional biological wastewater treatment is not efficient to remove SMX, photolysis in natural waters can represent an important transformation pathway. It was recently shown that SMX transformation products can retain antibiotic activity. Therefore, it is crucial to better understand photochemical processes occurring in natural water just as the formation of active transformation products (TPs). During long-term SMX photolysis experiments (one week), nine TPs were identified by reference standards. Moreover, five further TPs of photodecomposition of SMX were found. For the first time, a TP with m/z 271 [M + H] + was observed during photolysis and tentatively confirmed as 4,x-dihydroxylated SMX. The DOC mass balance clearly showed that only around 5 to 10% were mineralized during the experiment emphasizing the need to elucidate the fate of TPs. Bacterial bioassays confirmed that the mixture retains its antibiotic toxicity toward luminescence (24 h) and that there is no change over the treatment time on EC 50 . In contrast, growth inhibition activity was found to slightly decrease over the irradiation time. However, this decrease was not proportional to the transformation of the parent compound SMX. - Highlights: • During SMX photolysis experiments, nine TPs were identified by reference standards. • Six further TPs of SMX phototransformation were found. • A TP with a m/z 271 was tentatively confirmed as 4-,x-dihydroxylated SMX. • The mixture exhibitsluminescence inhibition without changes over the irradiation time. • Growth inhibition was found to slightly decrease over the irradiation time.

  6. Antioxidant activity of methanolic extracts from three coriander (Coriandrum sativum L. fruit varieties

    Directory of Open Access Journals (Sweden)

    Kamel Msaada

    2017-05-01

    Full Text Available In this study, fruit methanolic extract of three coriander (Coriandrum sativum L. varieties (Tunisian, Syrian and Egyptian was assayed for their antioxidant activities. Obtained results showed that there are significant (P < 0.05 variations in total polyphenols (0.94 ± 0.05–1.09 ± 0.02 mg GAE/g DW, total flavonoids (2.03 ± 0.04–2.51 ± 0.08 mg EC/g DW and total condensed tannin (0.09 ± 0.01–0.17 ± 0.01 mg EC/g DW contents. The RP-HPLC analysis revealed the identification of phenolics in coriander fruits with chlorogenic and gallic acids as main compounds in Tunisian, Syrian and Egyptian varieties, respectively. Moreover, fruit methanolic extracts exhibited remarkable DPPH radical scavenging activity with IC50 values ranged from 27.00 ± 6.57 to 36.00 ± 3.22 μg/mL. EC50 values of reducing power activity varied significantly (P < 0.05 from 54.20 ± 6.22 to 122.01 ± 13.25 μg/mL. The IC50 values of β-carotene bleaching assay were between 160.00 ± 18.63 and 240.00 ± 26.35 μg/mL. Our results indicated that coriander fruit might constitute a rich and novel source of natural antioxidants and may be suggested as a new potential source of natural antioxidant and could be used as food additive.

  7. The susceptibility of circulating human influenza viruses to tizoxanide, the active metabolite of nitazoxanide.

    Science.gov (United States)

    Tilmanis, Danielle; van Baalen, Carel; Oh, Ding Yuan; Rossignol, Jean-Francois; Hurt, Aeron C

    2017-11-01

    Nitazoxanide is a thiazolide compound that was originally developed as an anti-parasitic agent, but has recently been repurposed for the treatment of influenza virus infections. Thought to exert its anti-influenza activity via the inhibition of hemagglutinin maturation and intracellular trafficking in infected cells, the effectiveness of nitazoxanide in treating patients with non-complicated influenza is currently being assessed in phase III clinical trials. Here, we describe the susceptibility of 210 seasonal influenza viruses to tizoxanide, the active circulating metabolite of nitazoxanide. An optimised cell culture-based focus reduction assay was used to determine the susceptibility of A(H1N1)pdm09, A(H3N2), and influenza B viruses circulating in the southern hemisphere from the period March 2014 to August 2016. Tizoxanide showed potent in vitro antiviral activity against all influenza viruses tested, including neuraminidase inhibitor-resistant viruses, allowing the establishment of a baseline level of susceptibility for each subtype. Median EC 50 values (±IQR) of 0.48 μM (0.33-0.71), 0.62 μM (0.56-0.75), 0.66 μM (0.62-0.69), and 0.60 μM (0.51-0.67) were obtained for A(H1N1)pdm09, A(H3N2), B(Victoria lineage), and B(Yamagata lineage) influenza viruses respectively. There was no significant difference in the median baseline tizoxanide susceptibility for each influenza subtype tested. This is the first report on the susceptibility of circulating viruses to tizoxanide. The focus reduction assay format described is sensitive, robust, and less laborious than traditional cell based antiviral assays, making it highly suitable for the surveillance of tizoxanide susceptibility in circulating seasonal influenza viruses. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Structure-Activity Relationships Based on 3D-QSAR CoMFA/CoMSIA and Design of Aryloxypropanol-Amine Agonists with Selectivity for the Human β3-Adrenergic Receptor and Anti-Obesity and Anti-Diabetic Profiles

    Directory of Open Access Journals (Sweden)

    Marcos Lorca

    2018-05-01

    Full Text Available The wide tissue distribution of the adrenergic β3 receptor makes it a potential target for the treatment of multiple pathologies such as diabetes, obesity, depression, overactive bladder (OAB, and cancer. Currently, there is only one drug on the market, mirabegron, approved for the treatment of OAB. In the present study, we have carried out an extensive structure-activity relationship analysis of a series of 41 aryloxypropanolamine compounds based on three-dimensional quantitative structure-activity relationship (3D-QSAR techniques. This is the first combined comparative molecular field analysis (CoMFA and comparative molecular similarity index analysis (CoMSIA study in a series of selective aryloxypropanolamines displaying anti-diabetes and anti-obesity pharmacological profiles. The best CoMFA and CoMSIA models presented values of r2ncv = 0.993 and 0.984 and values of r2test = 0.865 and 0.918, respectively. The results obtained were subjected to extensive external validation (q2, r2, r2m, etc. and a final series of compounds was designed and their biological activity was predicted (best pEC50 = 8.561.

  9. Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 and STS-135.

    Science.gov (United States)

    De Luca, Maria Antonietta; Castelli, M Paola; Loi, Barbara; Porcu, Alessandra; Martorelli, Mariella; Miliano, Cristina; Kellett, Kathryn; Davidson, Colin; Stair, Jacqueline L; Schifano, Fabrizio; Di Chiara, Gaetano

    2016-06-01

    In order to investigate the in vivo dopamine (DA) stimulant properties of selected 3rd generation Spice/K2 cannabinoids, BB-22, 5F-PB-22, 5F-AKB-48 and STS-135, their in vitro affinity and agonist potency at native rat and mice CB1 receptors was studied. The compounds bind with high affinity to CB1 receptors in rat cerebral cortex homogenates and stimulate CB1-induced [(35)S]GTPγS binding with high potency and efficacy. BB-22 and 5F-PB-22 showed the lowest Ki of binding to CB1 receptors (0.11 and 0.13 nM), i.e., 30 and 26 times lower respectively than that of JWH-018 (3.38 nM), and a potency (EC50, 2.9 and 3.7 nM, respectively) and efficacy (Emax, 217% and 203%, respectively) as CB1 agonists higher than JWH-018 (EC50, 20.2 nM; Emax, 163%). 5F-AKB-48 and STS-135 had higher Ki for CB1 binding, higher EC50 and lower Emax as CB1 agonists than BB-22 and 5F-PB-22 but still comparatively more favourable than JWH-018. The agonist properties of all the compounds were abolished or drastically reduced by the CB1 antagonist/inverse agonist AM251 (0.1 μM). No activation of G-protein was observed in CB1-KO mice. BB-22 (0.003-0.01 mg/kg i.v.) increased dialysate DA in the accumbens shell but not in the core or in the medial prefrontal cortex, with a bell shaped dose-response curve and an effect at 0.01 mg/kg and a biphasic time-course. Systemic AM251 (1.0 mg/kg i.p.) completely prevented the stimulant effect of BB-22 on dialysate DA in the NAc shell. All the other compounds increased dialysate DA in the NAc shell at doses consistent with their in vitro affinity for CB1 receptors (5F-PB-22, 0.01 mg/kg; 5F-AKB-48, 0.1 mg/kg; STS-135, 0.15 mg/kg i.v.). 3rd generation cannabinoids can be even more potent and super-high CB1 receptor agonists compared to JWH-018. Future research will try to establish if these properties can explain the high toxicity and lethality associated with these compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Synergistic effect of apple extracts and quercetin 3-beta-d-glucoside combination on antiproliferative activity in MCF-7 human breast cancer cells in vitro.

    Science.gov (United States)

    Yang, Jun; Liu, Rui Hai

    2009-09-23

    Breast cancer is the most frequently diagnosed cancer in women. An alternative strategy to reduce the risk of cancer is through dietary modification. Although phytochemicals naturally occur as complex mixtures, little information is available regarding possible additive, synergistic, or antagonistic interactions among compounds. The antiproliferative activity of apple extracts and quercetin 3-beta-d-glucoside (Q3G) was assessed by measurement of the inhibition of MCF-7 human breast cancer cell proliferation. Cell cytotoxicity was determined by the methylene blue assay. The two-way combination of apple plus Q3G was conducted. In this two-way combination, the EC(50) values of apple extracts and Q3G were 2- and 4-fold lower, respectively, than those of apple extracts and Q3G alone. The combination index (CI) values at 50 and 95% inhibition rates were 0.76 +/- 0.16 and 0.42 +/- 0.10, respectively. The dose-reduction index (DRI) values of the apple extracts and Q3G to achieve a 50% inhibition effect were reduced by 2.03 +/- 0.55 and 4.28 +/- 0.39-fold, respectively. The results suggest that the apple extracts plus Q3G combination possesses a synergistic effect in MCF-7 cell proliferation.

  11. Bactericidal and antibiofilm activity of bactenecin-derivative peptides against the food-pathogen Listeria monocytogenes: New perspectives for food processing industry.

    Science.gov (United States)

    Palmieri, Gianna; Balestrieri, Marco; Capuano, Federico; Proroga, Yolande T R; Pomilio, Francesco; Centorame, Patrizia; Riccio, Alessia; Marrone, Raffaele; Anastasio, Aniello

    2018-08-20

    Antimicrobial peptides have received great attention for their potential benefits to extend the shelf-life of food-products. Innate defense regulator peptide-1018 (IDR-1018) represents a promising candidate for such applications, due to its broad-spectrum antimicrobial activity, although food-isolated pathogens have been poorly investigated. Herein, we describe the design and the structural-functional characterization of a new 1018-derivative peptide named 1018-K6, in which the alanine in position 6 was replaced with a lysine. Spectroscopic analysis revealed a noticeable switch from β-sheet to helical conformations of 1018-K6 respect to IDR-1018, with a faster folding kinetic and increased structural stability. Moreover, 1018-K6 evidenced a significant antibiofilm/bactericidal efficiency specifically against Listeria monocytogenes isolates from food-products and food-processing environments, belonging to serotype 4b involved in the majority of human-listeriosis cases, with EC 50 values two- five-fold lower than those measured for IDR-1018. Therefore, a single amino-acid substitution in IDR-1018 sequence produced severe changes in peptide conformation and antimicrobial performances. Published by Elsevier B.V.

  12. Purification, crystallization and preliminary X-ray diffraction analysis of an acidic phospholipase A2 with vasoconstrictor activity from Agkistrodon halys pallas venom

    International Nuclear Information System (INIS)

    Zou, Zhisong; Zeng, Fuxing; Zhang, Lu; Niu, Liwen; Teng, Maikun; Li, Xu

    2012-01-01

    A vasoconstrictor PLA 2 was purified from Agkistrodon halys pallas venom and the preliminary X-ray diffraction analysis had been described. Phospholipases A 2 (PLA 2 s) are the major component of snake venoms and exert a variety of relevant toxic actions such as neurotoxicity and myotoxicity, amongst others. An acidic PLA 2 , here named AhV-aPA, was purified from Agkistrodon halys pallas venom by means of a three-step chromatographic procedure. AhV-aPA migrated as a single band on SDS–PAGE gels, with a molecular weight of about 14 kDa. Like other acidic aPLA 2 s, AhV-aPA has high enzymatic activity. Tension measurements of mouse thoracic aortic rings remarkably indicated that AhV-aPA could induce a further contractile response on the 60 mM K + -induced contraction, with an EC 50 of 369 nmol l −1 . Rod-shaped crystals were obtained by the hanging-drop vapour-diffusion method and diffracted to a resolution limit of 2.30 Å. The crystals belonged to space group P222, with unit-cell parameters a = 44.27, b = 68.39, c = 81.54 Å

  13. Chemical and ecotoxicological analyses of sediments and elutriates of contaminated rivers due to e-waste recycling activities using a diverse battery of bioassays

    Energy Technology Data Exchange (ETDEWEB)

    Wang, F.; Leung, A.O.W.; Wu, S.C.; Yang, M.S. [Croucher Institute for Environmental Sciences, and Department of Biology, Hong Kong Baptist University, Kowloon Tong (Hong Kong); Wong, M.H., E-mail: mhwong@hkbu.edu.h [Croucher Institute for Environmental Sciences, and Department of Biology, Hong Kong Baptist University, Kowloon Tong (Hong Kong)

    2009-07-15

    A multi-trophic, multi-exposure phase assessment approach was applied to characterize the toxicity of sediments collected from two rivers in Guiyu, China, an e-waste recycling centre. Elutriate toxicity tests (bacterium Vibrio fischeri and microalga Selenastrum capricornutum) and whole sediment toxicity test (crustacean Heterocypris incongruens) showed that most sediments exhibited acute toxicity, due to elevated heavy metals and PAHs levels, and low pH caused by uncontrolled acid discharge. The survival rates of crustaceans were negatively (p < 0.05) correlated with total PAHs in sediments (411-1755 mg kg{sup -1}); EC50s of V. fischeri on the elutriates were significantly correlated with elutriate pH (p < 0.01). Significant (p < 0.05) correlations between the induction of hepatic metallothionein in tilapia (Oreochromis mossambicus) and metal concentrations (Cu, Zn, Pb) in sediments were also observed, when fish were fed with diets containing sediment. The results showed that uncontrolled e-waste recycling activities may bring adverse effects to local aquatic ecosystem. - Toxicity tests using different trophic organisms provided important information, supplementing chemical analyses.

  14. Estrogenic activity and estrogen receptor β binding of the UV filter 3-benzylidene camphor Comparison with 4-methylbenzylidene camphor

    International Nuclear Information System (INIS)

    Schlumpf, Margret; Jarry, Hubert; Wuttke, Wolfgang; Ma, Risheng; Lichtensteiger, Walter

    2004-01-01

    UV filters represent new classes of estrogenic [Environ. Health Perspect. 109 (2001) 239] or antiandrogenic [Toxicol. Sci. 74 (2003) 43] chemicals. We tested 3-benzylidene camphor (3-BC), reported as estrogenic in fish [Pharmacol. Toxicol. 91 (2002) 204], and mammalian systems in comparison to 4-methylbenzylidene camphor (4-MBC), shown to be active in rats, and analyzed binding to estrogen receptor subtypes. 3-BC and 4-MBC stimulated MCF-7 cell proliferation (EC 50 : 0.68 and 3.9 μM). The uterotrophic assay of 3-BC (oral gavage) in immature rats showed unexpected potency with ED50 45.3 mg/kg per day; lowest effective dose 2 mg/kg per day, and maximum effect with 70% of ethinylestradiol. After comparing with literature data, we found that the oral 3-BC was considerably more potent than oral bisphenol A and almost as active as subcutaneous genistein. 3-BC and 4-MBC displaced 16α 125 I-estradiol from porcine uterine cytosolic receptors (IC 50 : 14.5 and 112 μM), and from recombinant human estrogen receptor β (hERβ) (IC 50 : 3-BC, 11.8 μM; 4-MBC, 35.3 μM), whereas no displacement was detected at human estrogen receptor α (hERα) up to 3 mM. This subtype selectivity makes the two camphor derivatives interesting model compounds. Their activity on immature rat uterus is not easily explained by ERβ activation. It cannot be excluded that active metabolites with possibly different receptor binding characteristics are formed in vivo

  15. Polystyrene nanoparticles activate ion transport in human airway epithelial cells

    Directory of Open Access Journals (Sweden)

    McCarthy J

    2011-06-01

    Full Text Available J McCarthy1, X Gong2, D Nahirney2, M Duszyk2, MW Radomski11School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, Dublin, Ireland; 2Department of Physiology, University of Alberta, Edmonton, Alberta, CanadaBackground: Over the last decade, nanotechnology has provided researchers with new nanometer materials, such as nanoparticles, which have the potential to provide new therapies for many lung diseases. In this study, we investigated the acute effects of polystyrene nanoparticles on epithelial ion channel function.Methods: Human submucosal Calu-3 cells that express cystic fibrosis transmembrane conductance regulator (CFTR and baby hamster kidney cells engineered to express the wild-type CFTR gene were used to investigate the actions of negatively charged 20 nm polystyrene nanoparticles on short-circuit current in Calu-3 cells by Ussing chamber and single CFTR Cl- channels alone and in the presence of known CFTR channel activators by using baby hamster kidney cell patches.Results: Polystyrene nanoparticles caused sustained, repeatable, and concentration-dependent increases in short-circuit current. In turn, these short-circuit current responses were found to be biphasic in nature, ie, an initial peak followed by a plateau. EC50 values for peak and plateau short-circuit current responses were 1457 and 315.5 ng/mL, respectively. Short-circuit current was inhibited by diphenylamine-2-carboxylate, a CFTR Cl- channel blocker. Polystyrene nanoparticles activated basolateral K+ channels and affected Cl- and HCO3- secretion. The mechanism of short-circuit current activation by polystyrene nanoparticles was found to be largely dependent on calcium-dependent and cyclic nucleotide-dependent phosphorylation of CFTR Cl- channels. Recordings from isolated inside-out patches using baby hamster kidney cells confirmed the direct activation of CFTR Cl- channels by the nanoparticles.Conclusion: This is the first study to identify

  16. Dioxin activation of CYP1A5 promoter/enhancer regions from two avian species, common cormorant (Phalacrocorax carbo) and chicken (Gallus gallus): Association with aryl hydrocarbon receptor 1 and 2 isoforms

    International Nuclear Information System (INIS)

    Lee, Jin-Seon; Kim, Eun-Young; Iwata, Hisato

    2009-01-01

    The present study focuses on the molecular mechanism and interspecies differences in susceptibility of avian aryl hydrocarbon receptor (AHR)-cytochrome P4501A (CYP1A) signaling pathway. By the cloning of 5'-flanking regions of CYP1A5 gene from common cormorant (Phalacrocorax carbo) and chicken (Gallus gallus), seven putative xenobiotic response elements (XREs) were identified within 2.7 kb upstream region of common cormorant CYP1A5 (ccCYP1A5), and six XREs were found within 0.9 kb of chicken CYP1A5 (ckCYP1A5). Analysis of sequential deletion and mutagenesis of the binding sites in avian CYP1A5 genes by in vitro reporter gene assays revealed that two XREs at -613 bp and -1585 bp in ccCYP1A5, and one XRE at -262 bp in ckCYP1A5 conferred TCDD-responsiveness. The binding of AHR1 with AHR nuclear translocator 1 (ARNT1) to the functional XRE in a TCDD-dependent manner was verified with gel shift assays, suggesting that avian CYP1A5 is induced by TCDD through AHR1/ARNT1 signaling pathway as well as mammalian CYP1A1 but through a distinct pathway from mammalian CYP1A2, an ortholog of the CYP1A5. TCDD-EC 50 for the transcriptional activity in both cormorant AHR1- and AHR2-ccCYP1A5 reporter construct was 10-fold higher than that in chicken AHR1-ckCYP1A5 reporter construct. In contrast, chicken AHR2 showed no TCDD-dependent response. The TCDD-EC 50 for CYP1A5 transactivation was altered by switching AHR1 between the two avian species, irrespective of the species from which the regulatory region of CYP1A5 gene originates. Therefore, the structural difference in AHR, not the CYP1A5 regulatory region may be a major factor to account for the dioxin susceptibility in avian species

  17. Effects of human pharmaceuticals on cytotoxicity, EROD activity and ROS production in fish hepatocytes

    International Nuclear Information System (INIS)

    Laville, N.; Aiet-Aiessa, S.; Gomez, E.; Casellas, C.; Porcher, J.M.

    2004-01-01

    Pharmaceuticals are found in the aquatic environment but their potential effects on non-target species like fish remain unknown. This in vitro study is a first approach in the toxicity assessment of human drugs on fish. Nine pharmaceuticals were tested on two fish hepatocyte models: primary cultures of rainbow trout hepatocytes (PRTH) and PLHC-1 fish cell line. Cell viability, interaction with cytochrome P450 1A (CYP1A) enzyme and oxidative stress were assessed by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrasodium bromide tetrazolium (MTT), 7-ethoxyresorufin-o-deethylase (EROD) and dichlorofluorescein (DCFH-DA) assays, respectively. The tested drugs were clofibrate (CF), fenofibrate (FF), carbamazepine (CBZ), fluoxetine (FX), diclofenac (DiCF), propranolol (POH), sulfamethoxazole (SFX), amoxicillin (AMX) and gadolinium chloride (GdCl 3 ). All substances were cytotoxic, except AMX at concentration up to 500 μM. The calculated MTT EC 50 values ranged from 2 μM (CF) to 651 μM (CBZ) in PLHC-1, and from 53 μM (FF) to 962 μM (GdCl 3 ) in PRTH. CF, FF, and FX were the most cytotoxic drugs and induced oxidative stress before being cytotoxic. Compared to hepatocytes from human and dog, fish hepatocytes seemed to be more susceptible to the peroxisome proliferators (PPs) CF and FF. In PLHC-1 cells none of the tested drugs induced the EROD activity whereas POH appeared as a weak EROD inducer in PRTH. Moreover, in PRTH, SFX, DiCF, CBZ and to a lesser extend, FF and CF inhibited the basal EROD activity at clearly sublethal concentrations which may be of concern at the biological and chemical levels in a multipollution context

  18. Biological activities and phytochemical profile of Passiflora mucronata from the Brazilian restinga

    Directory of Open Access Journals (Sweden)

    Marlon H. de Araujo

    Full Text Available ABSTRACT In general, Passiflora species have been reported for their folk medicinal use as sedative and anti-inflammatory. However, P. caerulea has already been reported to treat pulmonary diseases. Severe pulmonary tuberculosis, generally caused by Mycobacterium tuberculosis strains resistant to multiple drugs, can lead to deleterious inflammation and high mortality, encouraging new approaches in drug discovery. Thus, the aim of this work was to evaluate the Passiflora mucronata Lam., Passifloraceae, potential for tuberculosis treatment. Specifically, related to antimycobacterial activity and anti-inflammatory related effects (based on inhibition of nitric oxide, tumor necrosis factor-alpha production and antioxidant potential, as well as the chemical profile of P. mucronata. High performance liquid chromatography coupled with diode-array ultraviolet and mass spectrometer analyses of crude hydroalcoholic extract and ethyl acetate fraction showed the presence of flavonoids. Ethyl acetate fraction showed to be as antioxidant as Ginkgo biloba standard extract with EC50 of 14.61 ± 1.25 µg/ml. One major flavonoid isolated from ethyl acetate fraction was characterized as isoorientin. The hexane fraction and its main isolated compound, the triterpene β-amyrin, exhibited significant growth inhibitory activity against Mycobacterium bovis BCG (MIC50 1.61 ± 1.43 and 3.93 ± 1.05 µg/ml, respectively. In addition, Passiflora mucronata samples, specially hexane and dichloromethane fractions, as well as pure β-amyrin, showed a dose-related inhibition of lipopolysaccharide (LPS-induced nitric oxide production. In conclusion, Passiflora mucronata presented relevant biological potential and should be considered for further studies using in vivo pulmonary tuberculosis model.

  19. Evaluation of the effects of active fractions of chinese medicine formulas on IL-1β, IL-6, and TNF-α release from ANA-1 murine macrophages.

    Science.gov (United States)

    Ni, Li-Jun; Wang, Nan-Nan; Zhang, Li-Guo; Guo, Yan-Zi; Shi, Wan-Zhong

    2016-02-17

    Yaotongning (YTN) is a traditional Chinese Medicine (TCM) that contains ten component medicinal materials (CMMs) and uses Chinese rice wine as a vehicle to enhance its efficacy. YTN has been used for rheumatoid arthritis (RA) treatment in China for decades and has been reported to have anti-inflammatory and analgesic effects, as well as to strengthen the immune system. The present work quantitatively evaluated the in vitro effects of active fractions from the ten CMMs that make up YTN and eight additional herbs commonly used in TCM formulas for RA treatment, as well as different combinations of these active fractions, on cellular immune response; the findings were used to determine which active fractions are responsible for promoting an immune response, and to assess whether YTN is superior to other similar formulas and whether YTN can be improved by simplifying its formula from the point of its cellular immunomodulatory activity. Using the YTN formulation principles and some concepts in combinatorial chemistry, 27 TCM samples were designed by combining some or all of the active fractions of YTN and other eight herbs used for RA treatment. Release of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) from ANA-1 murine macrophages was measured using an enzyme-linked immunosorbent assay (ELISA). The immunoregulatory effects of the TCM samples were evaluated by comparing their half-effective concentrations (EC50) for stimulating the release of these cytokines. Among the investigated active fractions, the flavonoids from Carthamus tinctorius (Fct), Davallia mariesii (Fdm), and Cinnamomum cassia Twig volatile oils (Vca) from the eight selected herbs effectively promoted IL-1β and IL-6 release from ANA-1 cells. Saponins from the YTN CMM Glycyrrhiza uralensis (Sgu) were the most potent promoters of IL-1β and TNF-α release. The aqueous extract of YTN CMM Eupolyphaga sinensis (Ves) strongly enhanced the release of IL-1β, IL-6, and

  20. Antiproliferative activity in tumor cell lines, antioxidant capacity and total phenolic, flavonoid and tannin contents of Myrciaria floribunda

    Directory of Open Access Journals (Sweden)

    LUIS A.C. TIETBOHL

    Full Text Available ABSTRACT Myrciaria floribunda (H. West ex Willd. O. Berg, Myrtaceae, is a native plant species of the Atlantic Rain Forest, from north to south of Brazil. The lyophilized ethyl acetate extract from the leaves of M. floribunda was investigated for its antiproliferative activity in tumor cell lines, antioxidant capacity and its total phenolic, flavonoid and tannin contents. Antiproliferative activity was tested in vitro against seven human cancer cells and against immortalized human skin keratinocytes line (HaCat, no cancer cell. Antioxidant activity was determined using 1-diphenyl-2-picrylhydrazyl (DPPH radical scavenging and oxygen radical absorbing capacity (ORAC assays and total phenolic, flavonoid and tannin contents were determined by spectrophotometric techniques. Ethyl acetate extract of M. floribunda exhibited antiproliferative activity against cancer cell lines with total growth inhibition (TGI between 69.70 and 172.10 µg/mL. For HaCat cell, TGI value was 213.60 µg/mL. M. floribunda showed a strong antioxidant potential: EC50 of 45.89±0.42 µg/mL and 0.55±0.05 mmol TE/g for DPPH and ORAC, respectively. Total phenolic content was 0.23±0.013g gallic acid equivalents (GAE/g extract and exhibited 13.10±1.60% of tannins content. The content of flavonoid was 24.08±0.44% expressed as rutin equivalents. These results provide a direction for further researches about the antitumoral potential of M. floribunda.

  1. In vitro antioxidant activity of different cultivars of banana flower (Musa paradicicus L.) extracts available in India.

    Science.gov (United States)

    China, Ratna; Dutta, Sanjukta; Sen, Sauradip; Chakrabarti, Rajarshi; Bhowmik, Debajit; Ghosh, Santinath; Dhar, Pubali

    2011-01-01

    Six different cultivars of banana flowers (Musa paradicicus) (Kathali, Bichi, Shingapuri, Kacha, Champa, and Kalabou) were analyzed for the content of polyphenol expressed as gallic acid equivalent and flavonoid expressed as quercetein equivalent, and the in vitro total antioxidative activities of the flower extracts were compared with standard and expressed as trolox equivalent. The reducing power, 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•(+)) scavenging activities, inhibition of lipid peroxidation in a linoleic acid emulsion system, and liposome peroxidation system were measured and compared with respective standard antioxidants. Iron-mediated Fenton reaction was carried out to evaluate the protective effect of the extract of banana flower (Kacha cultivar) against H(2)O(2)-induced DNA damage. The Kacha variety contains the maximum amount of polyphenol (11.94 ± 0.03 mg of gallic acid equivalent/g of dry weight) and flavonoid (0.174 ± 0.001 g of quercetin equivalent/g of polyphenol). It also has the highest total antioxidant capacity, DPPH radical scavenging activity, and ABTS•(+) radical scavenging activity with a least EC(50) value of 0.051 mg/mL. Hepatic cell damage in iron-mediated Fenton reaction caused by free radicals is reduced by the banana flower extract. On the basis of the results obtained, the banana flowers are found to be a potential source of natural antioxidants. This is the first report on the antioxidant properties of the extracts from banana flowers. The study suggests that the flowers of M. paradicicus that are found in India and consumed as vegetable can provide valuable functional ingredients that help in the prevention of oxidative stress. © 2011 Institute of Food Technologists®

  2. Antioxidant and Antibacterial Activity of the Beverage Obtained by Fermentation of Sweetened Lemon Balm (Melissa offi cinalis L. Tea with Symbiotic Consortium of Bacteria and Yeasts

    Directory of Open Access Journals (Sweden)

    Dragoljub D. Cvetković

    2014-01-01

    Full Text Available Kombucha is a fermented tea beverage which is traditionally prepared by fermenting sweetened black or green tea (Camellia sinensis L. with symbiotic consortium of bacteria and yeasts (SCOBY. In this study, lemon balm (Melissa offi cinalis L. was used as the only nitrogen source for kombucha fermentation. During the seven-day fermentation process, pH value, titratable acidity (TA, total phenolic content, phenolic compounds, and antioxidant activity against hydroxyl (˙OH and 1,1-diphenyl-2-picrylhydrazil (DPPH radicals were measured to detect the connection between the fermentation time and antioxidant and antibacterial activities of lemon balm kombucha. Antibacterial activity of fi nished beverages with optimum acidity (TA=4–4.5 g/L, the value which is confi rmed by long-time kombucha consumers, and enhanced acidity (TA=8.12 g/L was tested against eleven wild bacterial strains. The results showed that lemon balm could be successfully used as an alternative to C. sinensis L. for kombucha fermentation. Total phenolic content and antioxidant activity against DPPH radicals of lemon balm fermentation broth were higher than those of traditional kombucha. Rosmarinic acid is the main phenolic compound of the lemon balm-based kombucha that probably provides biological activity of the beverage. Judging from the EC50 values, kombucha beverages exhibited higher antioxidant activities compared with C. sinensis L. and M. offi cinalis L. infusions, which can probably be ascribed to SCOBY metabolites. Lemon balm kombucha with both optimum and enhanced acidity showed antibacterial activity, which can be primarily ascribed to acetic acid, but also to some other tea components and SCOBY metabolites.

  3. Antioxidant and Antibacterial Activity of the Beverage Obtained by Fermentation of Sweetened Lemon Balm
(Melissa officinalis L.) Tea with Symbiotic Consortium 
of Bacteria and Yeasts.

    Science.gov (United States)

    Velićanski, Aleksandra S; Cvetković, Dragoljub D; Markov, Siniša L; Šaponjac, Vesna T Tumbas; Vulić, Jelena J

    2014-12-01

    Kombucha is a fermented tea beverage which is traditionally prepared by fermenting sweetened black or green tea ( Camellia sinensis L.) with symbiotic consortium of bacteria and yeasts (SCOBY). In this study, lemon balm ( Melissa officinalis L.) was used as the only nitrogen source for kombucha fermentation. During the seven-day fermentation process, pH value, titratable acidity (TA), total phenolic content, phenolic compounds, and antioxidant activity against hydroxyl ( ˙ OH) and 1,1-diphenyl-2-picrylhydrazil (DPPH) radicals were measured to detect the connection between the fermentation time and antioxidant and antibacterial activities of lemon balm kombucha. Antibacterial activity of finished beverages with optimum acidity (TA=4-4.5 g/L), the value which is confirmed by long-time kombucha consumers, and enhanced acidity (TA=8.12 g/L) was tested against eleven wild bacterial strains. The results showed that lemon balm could be successfully used as an alternative to C. sinensis L. for kombucha fermentation. Total phenolic content and antioxidant activity against DPPH radicals of lemon balm fermentation broth were higher than those of traditional kombucha. Rosmarinic acid is the main phenolic compound of the lemon balm-based kombucha that probably provides biological activity of the beverage. Judging from the EC 50 values, kombucha beverages exhibited higher antioxidant activities compared with C. sinensis L. and M. officinalis L. infusions, which can probably be ascribed to SCOBY metabolites. Lemon balm kombucha with both optimum and enhanced acidity showed antibacterial activity, which can be primarily ascribed to acetic acid, but also to some other tea components and SCOBY metabolites.

  4. Antioxidant Activity and Bioactive Components of Oxalidaceae Fruit Extracts

    International Nuclear Information System (INIS)

    Asna, N.A.; Noriham, A.

    2014-01-01

    The study was conducted to evaluate the Antioxidant Activity (AA), Total Flavonoid Content (TFC), and Total Phenolic Content (TPC) of Oxalidaceae fruit extracts. Two types of Averrhoa carambola L. and two types of bilimbi fruits were used in this study. Bilimbi fruits selected were Averrhoa bilimbi L. and Averrhoa bilimbi cv. while Averrhoa carambola L. selected were Averrhoa carambola L. (honey type) and another type of Averrhoa carambola L. which is known as tart type. The maturity stage for both Averrhoa carambola L. fruits (honey and tart type) were selected at commercial maturity stages which were stage 3 and stage 4. Antioxidant estimation of oxalidaceae fruit extracts were evaluated by using Total Flavonoid Content (TFC) and Total Phenolic Content (TPC), while antioxidant activity were evaluated using scavenging of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH), β-carotene Bleaching (BCB) and Ferric Reducing Antioxidant Power (FRAP) assays. Phytochemical screening of alkaloids, flavonoids, terpenoids, steroids, tannins and saponins were also performed on all samples. Averrhoa carambola L. indicated positive results for all phytochemical screening conducted and similar results were observed from bilimbi fruits, except for alkaloids. Averrhoa carambola L. (tart type) of stage 4 possessed higher TPC and TFC followed by Averrhoa carambola L. (honey type) of stage 4. Averrhoa carambola L. (tart type) of stage 4 also exhibited high scavenging effect (74 %) as determined by DPPH assay with the value of EC 50 72.36 mg/ ml while Averrhoa carambola L. (honey type) of stage 3 showed significantly lower percentage of scavenging effect. The results also demonstrated that FRAP values of Averrhoa carambola L. (honey type) of stage 4 and Averrhoa carambola L. (tart type) of stage 4 were higher than other samples (5.1023 mmol TE/ g and 5.0759 mmol TE/ g) and similar trends were observed for β-carotene Bleaching (BCB) assay, where Averrhoa carambola L. (honey type) of stage 4

  5. Silver nanoparticles: green synthesis using Phoenix dactylifera fruit extract, characterization, and anti-oxidant and anti-microbial activities

    Science.gov (United States)

    Shaikh, Anas Ejaz; Satardekar, Kshitij Vasant; Khan, Rummana Rehman; Tarte, Nanda Amit; Barve, Siddhivinayak Satyasandha

    2018-03-01

    Hydro-alcoholic (2:8 v/v) extract of the pulp of Phoenix dactylifera fruit pulp obtained using Soxhlet extraction (70 °C, 6 h) was found to contain alkaloids, sterols, tannins, flavonoids, cardiac glycosides, proteins, and carbohydrates. An aqueous solution (20% v/v) of the extract led to the synthesis of silver nanoparticles (AgNPs) from 0.01 M AgNO3 solution as confirmed by the surface plasmon resonance at 445 nm determined using UV-visible spectroscopy after 24 h. The synthesized AgNPs were found to be mostly spherical and complexed with phytochemicals from the extract. The size of AgNPs ranged from 12.2-140.2 nm with mean diameter of 47.0 nm as characterized by scanning electron microscopy (SEM). The elemental composition of the AgNPs complexed with the phytochemicals was found to be 80.49% silver (Ag), 15.21% carbon (C), and 4.30% oxygen (O) on a weight basis by energy-dispersive spectroscopy (EDS). Using the α,α-diphenyl-β-picrylhydrazyl (DPPH) assay, an anti-oxidant activity of 89.15% for 1 µg L-1 ultrasonically homogenized ethanolic solution of complexed AgNPs was obtained (equivalent to 0.20 mg mL-1 gallic acid solution), while methanolic solution of plant extract possessed an EC50 value of 3.45% (v/v) (equivalent to 0.11 mg mL-1 gallic acid solution). The plant-nanosilver broth was also found to possess effective anti-microbial activity against Escherichia coli ATCC 8739, Staphylococcus aureus ATCC 6538, and Candida albicans ATCC 10231 as assessed by the disc diffusion assay. However, the plant extract showed negligible anti-microbial activity.

  6. Survival, mobility, and membrane-bound enzyme activities of freshwater planarian, Dugesia japonica, exposed to synthetic and natural surfactants.

    Science.gov (United States)

    Li, Mei-Hui

    2012-04-01

    Surfactants are a major class of emerging pollutants widely used in large quantities in everyday life and commonly found in surface waters worldwide. Freshwater planarian was selected to examine the effects of different surfactants by measuring mortality, mobility, and membrane-bound enzyme activities. Among the 10 surfactants tested, the acute toxicities of betaine and polyethylene glycol (PEG-200) to planarians were relatively low, with a median lethal concentration (LC50) greater than 10,000 mg/L. The toxicity to planarians of the other eight surfactants based on 48-h LC50 could be arranged in the descending order of cetylpyridinum chloride (CPC) > 4-tert-octylphenol (4-tert-OP) > ammonium lauryl sulfate > benzalkonium chloride > saponin > sodium lauroylsarcosinate > dioctyl sulfosuccinate > dodecyl trimethyl ammonium bromide (DTAB). Both CPC and 4-tert-OP were very toxic to planarians, with 48-h LC50 values <1 mg/L. The median effective concentrations (EC50s) of planarian mobility were in the 0.1 to 50 mg/L range and were in the same range as the 24-h LC50 of planarians exposed to different surfactants, except for DTAB. In addition, significant inhibition of cholinesterase activity activities was found in planarians exposed to 4-tert-OP at 2.5 and 5 mg/L and to saponin at 10 mg/L after 2-h treatments. This result suggests that planarian mobility responses can be used as an alternative indicator for acute toxicity of surfactants after a very short exposure period. Copyright © 2012 SETAC.

  7. 4,5-Di-O-Caffeoylquinic Acid from Ligularia fischeri Suppresses Inflammatory Responses Through TRPV1 Activation.

    Science.gov (United States)

    Kim, Yiseul; Kim, Jung Tae; Park, Joonwoo; Son, Hee Jin; Kim, Eun-Young; Lee, Young Joo; Rhyu, Mee-Ra

    2017-10-01

    Ligularia fischeri (Ledeb.) Turcz., a perennial plant native to northeastern Asia, has long been used as folk remedies for the alleviation of inflammatory symptoms. We investigated whether the extract of L. fischeri (LFEx) and caffeoylquinic acid (CQA) derivatives, the pharmacologically active ingredients identified from L. fischeri, regulate inflammation via a transient receptor potential vanilloid 1 (TRPV1)-mediated pathway. Changes in intracellular Ca 2+ levels to the LFEx and trans-5-O-CQA, 3,4-di-O-CQA, 3,5-di-O-CQA, and 4,5-di-O-CQA were monitored in TRPV1-expressing human embryonic kidney cell HEK 293T. LFEx and 4,5-di-O-CQA (EC 50  = 69.34 ± 1.12 μM) activated TRPV1, and these activations were significantly inhibited by ruthenium red, a general blocker of TRP channels, and capsazepine, a specific antagonist of TRPV1. 4,5-Di-O-CQA has been determined having antiinflammatory effect under hypoxic conditions by detecting the expression of cyclooxygenase-2 (COX-2), a representative inflammatory marker, and cellular migration in human pulmonary epithelial A549 cells. 4,5-Di-O-CQA suppressed COX-2 expression and cell migration, and this inhibition was countered by co-treatment with capsazepine. This study provides evidence that L. fischeri is selective to inflammatory responses via a TRPV1-mediated pathway, and 4,5-di-O-CQA might play a key role to create these effects. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  8. Repellent activities of dichloromethane extract of Allium sativum (garlic) (Liliaceae) against Hyalomma rufipes (Acari).

    Science.gov (United States)

    Nchu, Felix; Magano, Solomon R; Eloff, Jacobus N

    2016-12-02

    Dichloromethane (DCM) extract of garlic (Allium sativum Linn.) bulbs was assessed for its repellent effect against the hard tick, Hyalomma rufipes (Acari: Ixodidae) using two tick behavioural bioassays; Type A and Type B repellency bioassays, under laboratory conditions. These bioassays exploit the questing behaviour of H. rufipes, a tick that in nature displays ambush strategy, seeking its host by climbing up on vegetation and attaching to a passing host. One hundred microlitres (100 µL) of the test solution containing DCM extract of garlic bulbs and DCM at concentrations of 0.35%, 0.7% or 1.4% w/v were evaluated. DCM only was used for control. Tick repellency increased significantly (R2 = 0.98) with increasing concentration (40.03% - 86.96%) yielding an EC50 of 0.45% w/v in Type B repellency bioassay. At concentration of 1.4% w/v, the DCM extract of garlic bulbs produced high repellency index of 87% (male ticks) and 87.5% (female ticks) in the Type A repellency bioassay. Only 4% avoidance of male ticks or female ticks was recorded in the Type B repellency bioassay. In the corresponding controls, the mean numbers of non-repelled male or female ticks were 80% and 41 males or 38 females of 50 ticks in the Type A and Type B repellency bioassays, respectively. The variations in the results could be attributed to the difference in tick repellent behaviours that were assessed by the two repellency bioassays; the Type A repellency bioassay assessed repellent effect of garlic extracts without discriminating between deterrence and avoidance whereas the Type B repellency bioassay only assessed avoidance response. Generally, DCM extract of garlic was repellent against H. rufipes, albeit weak tick repellency was obtained in the Type B repellency bioassay. Furthermore, this study established that the tick repellent activity of garlic extracts is predominantly by deterrence.

  9. Safflower oil: an integrated assessment of phytochemistry, antiulcerogenic activity, and rodent and environmental toxicity

    Directory of Open Access Journals (Sweden)

    Walber Toma

    Full Text Available Gastric ulcers are a significant medical problem and the development of complications lead to significant mortality rates worldwide. In Brazil, Carthamus tinctorius L., Asteraceae, seeds essential oil, the safflower oil, is currently used as a thermogenic compound and as treatment for problems related to the cardiovascular system. In this study, by Raman spectroscopy, it was shown that oleic and linoleic acids are the compounds present in higher concentrations in the safflower oil. We demonstrated that safflower oil (750 mg/kg, p.o. decrease the ulcerogenic lesions in mice after the administration of hydrochloric acid-ethanol. The gastric ulcers induced by non-steroidal anti-inflammatory drug (NSAID in mice treated with cholinomimetics were treated with four different doses of safflower oil, of which, the dose of 187.5 mg/kg (p.o. showed significant antiulcerogenic properties (**p < 0.01. Moreover, the safflower oil at doses of 187.5 mg/kg (i.d. increased the pH levels, gastric volume (**p < 0.01 and gastric mucus production (***p < 0.001, and decreased the total gastric acid secretion (***p < 0.001. The acute toxicity tests showed that safflower oil (5.000 mg/kg, p.o. had no effect on mortality or any other physiological parameter. Ecotoxicological tests performed using Daphnia similis showed an EC50 at 223.17 mg/l, and therefore safflower oil can be considered “non-toxic” based on the directive 93/67/EEC on risk assessment for new notified substances by European legislation. These results indicate that the antiulcer activity of Safflower oil may be due to cytoprotective effects, which serve as support for new scientific studies related to this pathology.

  10. Toxicity of ionic liquids: Database and prediction via quantitative structure–activity relationship method

    International Nuclear Information System (INIS)

    Zhao, Yongsheng; Zhao, Jihong; Huang, Ying; Zhou, Qing; Zhang, Xiangping; Zhang, Suojiang

    2014-01-01

    Highlights: • A comprehensive database on toxicity of ionic liquids (ILs) was established. • Relationship between structure and toxicity of IL has been analyzed qualitatively. • Two new QSAR models were developed for predicting toxicity of ILs to IPC-81. • Accuracy of proposed nonlinear SVM model is much higher than the linear MLR model. • The established models can be explored in designing novel green agents. - Abstract: A comprehensive database on toxicity of ionic liquids (ILs) is established. The database includes over 4000 pieces of data. Based on the database, the relationship between IL's structure and its toxicity has been analyzed qualitatively. Furthermore, Quantitative Structure–Activity relationships (QSAR) model is conducted to predict the toxicities (EC 50 values) of various ILs toward the Leukemia rat cell line IPC-81. Four parameters selected by the heuristic method (HM) are used to perform the studies of multiple linear regression (MLR) and support vector machine (SVM). The squared correlation coefficient (R 2 ) and the root mean square error (RMSE) of training sets by two QSAR models are 0.918 and 0.959, 0.258 and 0.179, respectively. The prediction R 2 and RMSE of QSAR test sets by MLR model are 0.892 and 0.329, by SVM model are 0.958 and 0.234, respectively. The nonlinear model developed by SVM algorithm is much outperformed MLR, which indicates that SVM model is more reliable in the prediction of toxicity of ILs. This study shows that increasing the relative number of O atoms of molecules leads to decrease in the toxicity of ILs

  11. Myotropic activity and immunolocalization of selected neuropeptides of the burying beetle Nicrophorus vespilloides (Coleoptera: Silphidae).

    Science.gov (United States)

    Urbański, Arkadiusz; Lubawy, Jan; Marciniak, Paweł; Rosiński, Grzegorz

    2018-01-15

    Burying beetles (Nicrophorus sp.) are necrophagous insects with developed parental care. Genome of Nicrophorus vespilloides has been recently sequenced, which makes them interesting model organism in behavioral ecology. However, we know very little about their physiology, including the functioning of their neuroendocrine system. In this study, one of the physiological activities of proctolin, myosuppressin (Nicve-MS), myoinhibitory peptide (Trica-MIP-5) and the short neuropeptide F (Nicve-sNPF) in N. vespilloides have been investigated. The tested neuropeptides were myoactive on N. vespilloides hindgut. After application of the proctolin increased hindgut contraction frequency was observed (EC 50 value was 5.47 × 10 -8 mol/L). The other tested neuropeptides led to inhibition of N. vespilloides hindgut contractions (Nicve-MS: IC 50 = 5.20 × 10 -5 mol/L; Trica-MIP-5: IC 50 = 5.95 × 10 -6 mol/L; Nicve-sNPF: IC 50 = 4.08 × 10 -5 mol/L). Moreover, the tested neuropeptides were immunolocalized in the nervous system of N. vespilloides. Neurons containing sNPF and MIP in brain and ventral nerve cord (VNC) were identified. Proctolin-immunolabeled neurons only in VNC were observed. Moreover, MIP-immunolabeled varicosities and fibers in retrocerebral complex were observed. In addition, our results have been supplemented with alignments of amino acid sequences of these neuropeptides in beetle species. This alignment analysis clearly showed amino acid sequence similarities between neuropeptides. Moreover, this allowed to deduce amino acid sequence of N. vespilloides proctolin (RYLPTa), Nicve-MS (QDVDHVFLRFa) and six isoforms of Nicve-MIP (Nicve-MIP-1-DWNRNLHSWa; Nicve-MIP-2-AWQNLQGGWa; Nicve-MIP-3-AWQNLQGGWa; Nicve-MIP-4-AWKNLNNAGWa; Nicve-MIP-5-SEWGNFRGSWa; Nicve-MIP-6- DPAWTNLKGIWa; and Nicve-sNPF-SGRSPSLRLRFa). © 2018 Institute of Zoology, Chinese Academy of Sciences.

  12. Development of diacyltetrol lipids as activators for the C1 domain of protein kinase C.

    Science.gov (United States)

    Mamidi, Narsimha; Gorai, Sukhamoy; Mukherjee, Rakesh; Manna, Debasis

    2012-04-01

    The protein kinase C (PKC) family of serine/threonine kinases is an attractive drug target for the treatment of cancer and other diseases. Diacylglycerol (DAG), phorbol esters and others act as ligands for the C1 domain of PKC isoforms. Inspection of the crystal structure of the PKCδ C1b subdomain in complex with phorbol-13-O-acetate shows that one carbonyl group and two hydroxyl groups play pivotal roles in recognition of the C1 domain. To understand the importance of two hydroxyl groups of phorbol esters in PKC binding and to develop effective PKC activators, we synthesized DAG like diacyltetrols (DATs) and studied binding affinities with C1b subdomains of PKCδ and PKCθ. DATs, with the stereochemistry of natural DAGs at the sn-2 position, were synthesized from (+)-diethyl L-tartrate in four to seven steps as single isomers. The calculated EC(50) values for the short and long chain DATs varied in the range of 3-6 μM. Furthermore, the fluorescence anisotropy values of the proteins were increased in the presence of DATs in a similar manner to that of DAGs. Molecular docking of DATs (1b-4b) with PKCδ C1b showed that the DATs form hydrogen bonds with the polar residues and backbone of the protein, at the same binding site, as that of DAG and phorbol esters. Our findings reveal that DATs represent an attractive group of C1 domain ligands that can be used as research tools or further structurally modified for potential drug development.

  13. Antioxidant activity of ethanolic extract from cultivated strawberries’ leaves (Fragariae folium

    Directory of Open Access Journals (Sweden)

    Stanojević Ljiljana P.

    2015-01-01

    Full Text Available Strawberry is a member of the rose family (Rosaceae, subfamily Rosoideae, tribe Potentilleae in the genus Fragaria. The cultivated varieties of commercial strawberries usually were designated as Fragaria ananassa. Root, leaf, flower and fruit have the healing properties. The strawberry leaves extract is used for blood cleaning, for treatment of oral inflammation, diarrhea, various gastro-intestinal inflammation, and hemorrhoids, as well as a diuretic. So far, many positive biological effects of strawberries (anticancer, antioxidant and anticoagulant effect have been proven. The purpose of this study was to evaluate the antioxidant potential of ethanolic extract from cultivated strawberries (Fragariae folium, varieties Senga Sengana by using different antioxidant assays (DPPH, FRAP, FIC, H2O2 and TBA-MDA. Ethanolic extract from strawberry leaves was obtained by reflux extraction at the boiling temperature. Total phenols and total flavonoids content was determined spectrophotometrically by the method of Folin-Ciocalteu and by method with AlCl3, respectively. In the extract was determined high content of total phenols, while the total flavonoid content is much lower. The concentrations of extract required to neutralize 50% of the initial concentration of DPPH radicals (EC50 after 20 minutes incubation and immediately after adding DPPH radical solution were 7,91 and 19,46 μgcm-3, respectively. Extract was achieved the maximum iron ions chelating ability (67.89% at a concentration of 2 mgcm-3. Inhibition of lipid peroxidation of 70% was achieved by extract concentration of 0.03125 mgcm-3, while the maximum neutralization of H2O2 (30.47% was achieved by extract concentration of 0.5 mgcm-3. FRAP value of the investigated extract is 284.51 mgFe/g of dry extract. Presented results of the antioxidant activity show that the obtained extract from the cultivated strawberry leaves is a potential source of natural antioxidants. [Projekat Ministarstva nauke

  14. The antimicrobial, antioxidative, anti-inflammatory activity and cytotoxicity of different fractions of four South African Bauhinia species used traditionally to treat diarrhoea.

    Science.gov (United States)

    Ahmed, Aroke S; Elgorashi, Esameldin E; Moodley, Nivan; McGaw, Lyndy J; Naidoo, Vinasan; Eloff, Jacobus N

    2012-10-11

    Many Bauhinia species, including those indigenous to South Africa, are used in traditional medicine across the world for treating ailments such as gastrointestinal tract (GIT) disorders, diabetes, infectious diseases and inflammation. Several relevant aspects of different fractions of leaf extracts of Bauhinia bowkeri (BAB), Bauhinia galpinii (BAG), Bauhinia petersiana (BAP), and Bauhinia variegata (BAV) used in South African traditional medicine to alleviate diarrhoea related symptoms were evaluated. The antioxidative activities of the extracts were determined using the 2, 2-diphenyl-1-picrylhydrazyl (DPPH), 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid (ABTS(+)) radical scavenging and ferric reducing antioxidant power (FRAP) methods. In vitro antimicrobial activities of the extracts were determined against bacterial strains (Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecalis) and clinical isolates of the opportunistic fungal strains (Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans) using a serial dilution microplate method. The polyphenolic contents were quantified using standard methods, and anti-inflammatory activities of the crude extracts were determined using the cyclooxygenase and soybean 15-lipoxygenase enzyme inhibitory assays. The safety of the extracts was evaluated by determining the cytotoxicity against Vero cell lines. The acidified 70% acetone crude extract and their fractions had good antiradical potency against the DPPH and ABTS radicals. The methanol soluble portions of the butanol fractions were more potent (EC(50) ranges from 0.64 ± 0.05 to 1.51 ± 0.07 and 0.88 ± 0.18 to 1.49 ± 0.09 μg/ml against DPPH and ABTS radical respectively) compared to the standard, trolox and ascorbic acid (EC(50) ranges from 1.47 ± 0.24 to 1.70 ± 0.27 μg/ml) for both DPPH and ABTS. The crude extracts contained variable quantities of phenolic content. The crude extracts and their fractions

  15. Real-time relationship between PKA biochemical signal network dynamics and increased action potential firing rate in heart pacemaker cells: Kinetics of PKA activation in heart pacemaker cells.

    Science.gov (United States)

    Yaniv, Yael; Ganesan, Ambhighainath; Yang, Dongmei; Ziman, Bruce D; Lyashkov, Alexey E; Levchenko, Andre; Zhang, Jin; Lakatta, Edward G

    2015-09-01

    cAMP-PKA protein kinase is a key nodal signaling pathway that regulates a wide range of heart pacemaker cell functions. These functions are predicted to be involved in regulation of spontaneous action potential (AP) generation of these cells. Here we investigate if the kinetics and stoichiometry of increase in PKA activity match the increase in AP firing rate in response to β-adrenergic receptor (β-AR) stimulation or phosphodiesterase (PDE) inhibition, that alters the AP firing rate of heart sinoatrial pacemaker cells. In cultured adult rabbit pacemaker cells infected with an adenovirus expressing the FRET sensor AKAR3, the EC50 in response to graded increases in the intensity of β-AR stimulation (by Isoproterenol) the magnitude of the increases in PKA activity and the spontaneous AP firing rate were similar (0.4±0.1nM vs. 0.6±0.15nM, respectively). Moreover, the kinetics (t1/2) of the increases in PKA activity and spontaneous AP firing rate in response to β-AR stimulation or PDE inhibition were tightly linked. We characterized the system rate-limiting biochemical reactions by integrating these experimentally derived data into a mechanistic-computational model. Model simulations predicted that phospholamban phosphorylation is a potent target of the increase in PKA activity that links to increase in spontaneous AP firing rate. In summary, the kinetics and stoichiometry of increases in PKA activity in response to a physiological (β-AR stimulation) or pharmacological (PDE inhibitor) stimuli match those of changes in the AP firing rate. Thus Ca(2+)-cAMP/PKA-dependent phosphorylation limits the rate and magnitude of increase in spontaneous AP firing rate. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Kaempferol stimulates large conductance Ca2+-activated K+ (BKCa) channels in human umbilical vein endothelial cells via a cAMP/PKA-dependent pathway

    Science.gov (United States)

    Xu, Y C; Leung, G P H; Wong, P Y D; Vanhoutte, P M; Man, R Y K

    2008-01-01

    Background and purpose: Kaempferol has been shown to possess a vasodilator effect but its mechanism of action remains unclear. In this study, experiments were carried out to study the effect of kaempferol on K+ channels in endothelial cells. Experimental approach: K+ channel activities in human umbilical vein endothelial cells (HUVECs) were studied by conventional whole cell and cell-attached patch-clamp electrophysiology. Key results: Kaempferol stimulated an outward-rectifying current in HUVECs in a dose-dependent manner with an EC50 value of 2.5±0.02 μM. This kaempferol-induced current was abolished by large conductance Ca2+-activated K+ (BKCa) channel blockers, such as iberiotoxin (IbTX) and charybdotoxin (ChTX), whereas the small conductance Ca2+-activated K+ (SKCa) channel blocker, apamin, and the voltage-dependent K+ (KV) channel blocker, 4-aminopyridine, had no effect. Cell-attached patches demonstrated that kaempferol increased the open probability of BkCa channels in HUVECs. Clamping intracellular Ca2+ did not prevent kaempferol-induced increases in outward current. In addition, the kaempferol-induced current was diminished by the adenylyl cyclase inhibitor SQ22536, the cAMP antagonist Rp-8-Br-cAMP and the PKA inhibitor KT5720, but was not affected by the guanylyl cyclase inhibitor ODQ, the cGMP antagonist Rp-8-Br-cGMP and the PKG inhibitor KT5823. The activation of BKCa channels by kaempferol caused membrane hyperpolarization of HUVECs. Conclusion and implications: These results demonstrate that kaempferol activates the opening of BKCa channels in HUVECs via a cAMP/PKA-dependent pathway, resulting in membrane hyperpolarization. This mechanism may partly account for the vasodilator effects of kaempferol. PMID:18493242

  17. In vitro effects of four native Brazilian medicinal plants in CYP3A4 mRNA gene expression, glutathione levels and P-glycoprotein activity.

    Directory of Open Access Journals (Sweden)

    Andre Luis Dias Araujo Mazzari

    2016-08-01

    Full Text Available Erythrina mulungu Benth. (Fabaceae, Cordia verbenacea A. DC. (Boraginaceae, Solanum paniculatum L. (Solanaceae and Lippia sidoides Cham. (Verbenaceae are medicinal plants species native to Brazil shortlisted by the Brazilian National Health System for future clinical use. However, nothing is known about their effects in metabolic and transporter proteins, which could potentially lead to herb-drug interactions (HDI. In this work we assess non-toxic concentrations (100μg/mL of their infusions for their in vitro ability to modulate CYP3A4 mRNA gene expression and intracellular glutathione levels in HepG2 cells, as well as P-glycoprotein (P-gp activity in vincristine-resistant Caco-2 cells (Caco-2 VCR. Their mechanisms of action were further studied by measuring the activation of human pregnane X receptor (hPXR in transiently co-transfected HeLa cells and the inhibition of γ-glutamyl transferase (GGT in HepG2 cells. Our results show that P-gp activity was not affected in any case and that only Solanum paniculatum was able to significantly change CYP3A4 mRNA gene expression (two-fold decrease, p<0.05, this being correlated with an antagonist effect upon hPXR (EC50 = 0.38mg/mL. Total intracellular glutathione levels were significantly depleted by exposure to Solanum paniculatum (-44%, p<0.001, Lippia sidoides (-12%, p<0.05 and Cordia verbenacea (-47%, p<0.001. The later plant extract was able to decrease GGT activity (-48%, p<0.01. In conclusion, this preclinical study shows that the administration of some of these herbal medicines may be able to cause disturbances to metabolic mechanisms in vitro. Although Erythrina mulungu appears safe in our tests, active pharmacovigilance is recommended for the other three species, especially in the case of Solanum paniculatum.

  18. Built environmental correlates of physical activity in China: A review.

    Science.gov (United States)

    Day, Kristen

    2016-06-01

    China faces growing levels of physical inactivity and obesity, associated with increasing urbanization and changing lifestyles in recent years. China is expanding its cities to accommodate a growing urban population. This paper identifies built environment factors that are associated with physical activity in China. Findings can inform urban design and development in China to support increased physical activity. This paper is modeled on a review of built environment correlates of walking by Saelens and Handy (2008). Saelens and Handy reviewed research in developed countries. The present paper reviews 42 empirical studies that were conducted in China and were published between 2006 and 2014. Results discuss the association of built environment features and physical activity for transportation, recreation and work. Studies focus on adults and on major cities. Data on the built environment is typically self-reported. Strongest evidence was found for the positive association of physical activity with proximal non-residential locations, pedestrian infrastructure, aesthetics, and non-park physical activity facilities, and for the negative association of physical activity with urban residence. In terms of physical activity for transportation, evidence is strongest for associations between physical activity for transportation and proximal non-residential locations. More research is needed on the built environment and physical activity, especially including research on significant features of Chinese cities, such as air pollution, high density levels, traffic safety, and others. Research on associations between built environment features and physical activity should consider the specific social and built environment contexts of Chinese cities.

  19. 17β-Estradiol Enhances ASIC Activity in Primary Sensory Neurons to Produce Sex Difference in Acidosis-Induced Nociception.

    Science.gov (United States)

    Qu, Zu-Wei; Liu, Ting-Ting; Ren, Cuixia; Gan, Xiong; Qiu, Chun-Yu; Ren, Ping; Rao, Zhiguo; Hu, Wang-Ping

    2015-12-01

    Sex differences have been reported in a number of pain conditions. Women are more sensitive to most types of painful stimuli than men, and estrogen plays a key role in the sex differences in pain perception. However, it is unclear whether there is a sex difference in acidosis-evoked pain. We report here that both male and female rats exhibit nociceptive behaviors in response to acetic acid, with females being more sensitive than males. Local application of exogenous 17β-estradiol (E2) exacerbated acidosis-evoked nociceptive response in male rats. E2 and estrogen receptor (ER)-α agonist 1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole, but not ERβ agonist 2,3-bis(4-hydroxyphenyl)-propionitrile, replacement also reversed attenuation of the acetic acid-induced nociceptive response in ovariectomized females. Moreover, E2 can exert a rapid potentiating effect on the functional activity of acid-sensing ion channels (ASICs), which mediated the acidosis-induced events. E2 dose dependently increased the amplitude of ASIC currents with a 42.8 ± 1.6 nM of EC50. E2 shifted the concentration-response curve for proton upward with a 50.1% ± 6.2% increase of the maximal current response to proton. E2 potentiated ASIC currents via an ERα and ERK1/2 signaling pathway. E2 also altered acidosis-evoked membrane excitability of dorsal root ganglia neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acidic stimuli. E2 potentiation of the functional activity of ASICs revealed a peripheral mechanism underlying this sex difference in acetic acid-induced nociception.

  20. A target-based high throughput screen yields Trypanosoma brucei hexokinase small molecule inhibitors with antiparasitic activity.

    Directory of Open Access Journals (Sweden)

    Elizabeth R Sharlow

    2010-04-01

    Full Text Available The parasitic protozoan Trypanosoma brucei utilizes glycolysis exclusively for ATP production during infection of the mammalian host. The first step in this metabolic pathway is mediated by hexokinase (TbHK, an enzyme essential to the parasite that transfers the gamma-phospho of ATP to a hexose. Here we describe the identification and confirmation of novel small molecule inhibitors of bacterially expressed TbHK1, one of two TbHKs expressed by T. brucei, using a high throughput screening assay.Exploiting optimized high throughput screening assay procedures, we interrogated 220,233 unique compounds and identified 239 active compounds from which ten small molecules were further characterized. Computation chemical cluster analyses indicated that six compounds were structurally related while the remaining four compounds were classified as unrelated or singletons. All ten compounds were approximately 20-17,000-fold more potent than lonidamine, a previously identified TbHK1 inhibitor. Seven compounds inhibited T. brucei blood stage form parasite growth (0.03EC(50<3 microM with parasite specificity of the compounds being demonstrated using insect stage T. brucei parasites, Leishmania promastigotes, and mammalian cell lines. Analysis of two structurally related compounds, ebselen and SID 17387000, revealed that both were mixed inhibitors of TbHK1 with respect to ATP. Additionally, both compounds inhibited parasite lysate-derived HK activity. None of the compounds displayed structural similarity to known hexokinase inhibitors or human African trypanosomiasis therapeutics.The novel chemotypes identified here could represent leads for future therapeutic development against the African trypanosome.

  1. Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

    Energy Technology Data Exchange (ETDEWEB)

    Gorrochategui, Eva; Pérez-Albaladejo, Elisabet [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Casas, Josefina [Department of Biomedicinal Chemistry, IQAC–CSIC, 08034 Barcelona, Catalonia (Spain); Lacorte, Sílvia, E-mail: slbqam@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Porte, Cinta, E-mail: cinta.porte@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain)

    2014-06-01

    The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

  2. Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

    International Nuclear Information System (INIS)

    Gorrochategui, Eva; Pérez-Albaladejo, Elisabet; Casas, Josefina; Lacorte, Sílvia; Porte, Cinta

    2014-01-01

    The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

  3. Kinetic analysis of DAF-FM activation by NO: toward calibration of a NO-sensitive fluorescent dye.

    Science.gov (United States)

    Namin, Shabnam M; Nofallah, Sara; Joshi, Mahesh S; Kavallieratos, Konstantinos; Tsoukias, Nikolaos M

    2013-01-15

    Nitric oxide (NO) research in biomedicine has been hampered by the absence of a method that will allow quantitative measurement of NO in biological tissues with high sensitivity and selectivity, and with adequate spatial and temporal resolution. 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM) is a NO sensitive fluorescence probe that has been used widely for qualitative assessment of cellular NO production. However, calibration of the fluorescent signal and quantification of NO concentration in cells and tissues using fluorescent probes, have provided significant challenge. In this study we utilize a combination of mathematical modeling and experimentation to elucidate the kinetics of NO/DAF-FM reaction in solution. Modeling and experiments suggest that the slope of fluorescent intensity (FI) can be related to NO concentration according to the equation: ddtFI=2αk(1)NO(2)O(2)DAF-FMkNO+DAF-FM where α is a proportionality coefficient that relates FI to unit concentration of activated DAF-FM, k(1) is the NO oxidation rate constant, and k was estimated to be 4.3±0.6. The FI slope exhibits saturation kinetics with DAF-FM concentration. Interestingly, the effective half-maximum constant (EC(50)) increases proportionally to NO concentration. This result is not in agreement with the proposition that N(2)O(3) is the NO oxidation byproduct that activates DAF-FM. Kinetic analysis suggests that the reactive intermediate should exhibit NO-dependent consumption and thus NO(2)() is a more likely candidate. The derived rate law can be used for the calibration of DAF-FM fluorescence and the quantification of NO concentration in biological tissues. Copyright © 2012 Elsevier Inc. All rights reserved.

  4. Untargeted metabolic profiling reveals geography as the strongest predictor of metabolic phenotypes of a cosmopolitan weed

    DEFF Research Database (Denmark)

    Ahlstrand, Natalie Eva Iwanycki; Havskov Reghev, Nicoline; Markussen, Bo

    2018-01-01

    Plants produce a multitude of metabolites that contribute to their fitness and survival, and play a role in local adaptation to environmental conditions. The effects of environmental variation is particularly well studied within the genus Plantago, however, previous studies have largely focused...

  5. Parental informal payments in Kyrgyzstani schools: Analyzing the strongest and the weakest link

    Directory of Open Access Journals (Sweden)

    Rubén Ruiz Ramas

    2016-07-01

    Full Text Available This paper aims to explain why parental informal payments emerge and then spread in different manners in Kyrgyzstani schools and to examine their interaction as informal institutions with the school as a formal one. It is argued that the main reason behind informal payments is the survival of the schools; parents' acceptance of them was a result of necessity. In a small percentage of experiences where marketization of public schools was successful, there was a socioeconomic segregation of pupils, advancing toward a de facto privatization of public schools. Then, while the key logic behind informal payments was the upgrading or elitization of schools, the nature of the engagement of givers and receivers was by choice rather than by necessity. Finally, following Helmke and Levitsky (2004, I link the survival strategy to a substitutive relationship to formal public school outcomes, and to the elitization strategy, a competing nature with the formal logic of Kyrgyzstani basic education. Special attention is given to the social function approach toward informal economy practices, and to the significance of social stratification on how those informal practices work. The paper focuses on the comparison of informal payments in two schools representing the two strategies previously described: an elitnaya school from the center of Bishkek, the 13th Gymnasium School; and the conventional 21st Middle School in the novostroika (new settlement of Enesay, the capital's periphery. The fieldwork of this research was developed in two stays during the months of July/August and October/November in 2011.

  6. Parental informal payments in Kyrgyzstani schools: Analyzing the strongest and the weakest link

    OpenAIRE

    Rubén Ruiz Ramas

    2016-01-01

    This paper aims to explain why parental informal payments emerge and then spread in different manners in Kyrgyzstani schools and to examine their interaction as informal institutions with the school as a formal one. It is argued that the main reason behind informal payments is the survival of the schools; parents' acceptance of them was a result of necessity. In a small percentage of experiences where marketization of public schools was successful, there was a socioeconomic segregation of pup...

  7. Strongest experimental constraints on SU(5)×U(1) supergravity models

    Science.gov (United States)

    Lopez, Jorge L.; Nanopoulos, D. V.; Park, Gye T.; Zichichi, A.

    1994-01-01

    We consider a class of well-motivated string-inspired flipped SU(5) supergravity models which include four supersymmetry-breaking scenarios: no-scale, strict no-scale, dilaton, and special dilaton, such that only three parameters are needed to describe all new phenomena (mt,tanβ,mg~). We show that the CERN LEP precise measurements of the electroweak parameters in the form of the ɛ1 variable and the CLEO II allowed range for B(b-->sγ) are at present the most important experimental constraints on this class of models. For mt>~155 (165) GeV, the ɛ1 constraint [at 90 (95)% C.L.] requires the presence of light charginos (m+/-χ1360 GeV, mq~sγ) constraint excludes a significant fraction of the otherwise allowed region in the (m+/-χ1,tanβ) plane (irrespective of the magnitude of the chargino mass), while future experimental improvements will result in decisive tests of these models. In light of the ɛ1 constraint, we conclude that the outlook for chargino and selectron detection at LEP II and at DESY HERA is quite favorable in this class of models.

  8. Strongest experimental constraints on SU(5)xU(1) supergravity models

    International Nuclear Information System (INIS)

    Lopez, J.L.; Nanopoulos, D.V.; Park, G.T.; Zichichi, A.

    1994-01-01

    We consider a class of well-motivated string-inspired flipped SU(5) supergravity models which include four supersymmetry-breaking scenarios: no-scale, strict no-scale, dilaton, and special dilaton, such that only three parameters are needed to describe all new phenomena (m t ,tanβ,m g ). We show that the CERN LEP precise measurements of the electroweak parameters in the form of the ε 1 variable and the CLEO II allowed range for B(b→sγ) are at present the most important experimental constraints on this class of models. For m t approx-gt 155 (165) GeV, the ε 1 constraint [at 90 (95)% C.L.] requires the presence of light charginos (m χ1 ± approx-lt 50--100 GeV depending on m t ). Since all sparticle masses are proportional to m g , m χ1 ± approx-lt 100 GeV implies m χ1 0 approx-lt 55 GeV, m χ2 0 approx-lt 100 GeV, m g approx-lt 360 GeV, m q approx-lt 350 (365) GeV, m e R approx-lt 80 (125) GeV, m e L approx-lt 120 (155) GeV, and m n u approx-lt 100 (140) GeV in the no-scale (dilaton) flipped SU(5) supergravity model. The B(b→sγ) constraint excludes a significant fraction of the otherwise allowed region in the (m χ1 ± ,tanβ) plane (irrespective of the magnitude of the chargino mass), while future experimental improvements will result in decisive tests of these models

  9. Strongest model-independent bound on the lifetime of Dark Matter

    CERN Document Server

    Audren, Benjamin; Mangano, Gianpiero; Serpico, Pasquale Dario; Tram, Thomas

    2014-01-01

    Dark Matter is essential for structure formation in the late Universe so it must be stable on cosmological time scales. But how stable exactly? Only assuming decays into relativistic particles, we report an otherwise model independent bound on the lifetime of Dark Matter using current cosmological data. Since these decays affect only the low-$\\ell$ multipoles of the CMB, the Dark Matter lifetime is expected to correlate with the tensor-to-scalar ratio $r$ as well as curvature $\\Omega_k$. We consider two models, including $r$ and $r+\\Omega_k$ respectively, versus data from Planck, WMAP, WiggleZ and Baryon Acoustic Oscillations, with or without the BICEP2 data (if interpreted in terms of primordial gravitational waves). This results in a lower bound on the lifetime of CDM given by 160Gyr (without BICEP2) or 200Gyr (with BICEP2) at 95% confidence level.

  10. Transient negative biochar effects on plant growth are strongest after microbial species loss

    NARCIS (Netherlands)

    Hol, (Gera) W.H.G.; Vestergård, M.; Ten Hooven, F.C.; Duyts, H.; Van de Voorde, T.F.J.; Bezemer, T. Martijn

    2017-01-01

    Biochar has been explored as an organic amendment to improve soil quality and benefit plant growth. The overall positive effects of biochar on crop yields are generally attributed to abiotic changes, while the alternative causal pathway via changes in soil biota is unexplored. We compared plant

  11. Representing Lithuania's strongest ally / Anne E. Derse ; interviewed by Rokas M. Tracevskis

    Index Scriptorium Estoniae

    Derse, Anne E., 1954-

    2011-01-01

    USA suursaadik Leedus räägib, et USA kavatseb kontrollida Mihhail Golovatovi juhtumiga tegeleva komisjoni tööd, rõhutab, et president Barack Obama tahab investeerida haridusse ja et USA-Leedu suhetes on julgeolekul tähtis osa. Leedu kogukonnast Ameerika Ühendriikides

  12. D90: The Strongest Contributor to Setting Time in Mineral Trioxide Aggregate and Portland Cement.

    Science.gov (United States)

    Ha, William N; Bentz, Dale P; Kahler, Bill; Walsh, Laurence J

    2015-07-01

    The setting times of commercial mineral trioxide aggregate (MTA) and Portland cements vary. It was hypothesized that much of this variation was caused by differences in particle size distribution. Two gram samples from 11 MTA-type cements were analyzed by laser diffraction to determine their particle size distributions characterized by their percentile equivalent diameters (the 10th percentile, the median, and the 90th percentile [d90], respectively). Setting time data were received from manufacturers who performed indentation setting time tests as specified by the standards relevant to dentistry, ISO 6786 (9 respondents) or ISO 9917.1 (1 respondent), or not divulged to the authors (1 respondent). In a parallel experiment, 6 samples of different size graded Portland cements were produced using the same cement clinker. The measurement of setting time for Portland cement pastes was performed using American Society for Testing and Materials C 191. Cumulative heat release was measured using isothermal calorimetry to assess the reactions occurring during the setting of these pastes. In all experiments, linear correlations were assessed between setting times, heat release, and the 3 particle size parameters. Particle size varied considerably among MTA cements. For MTA cements, d90 was the particle size characteristic showing the highest positive linear correlation with setting time (r = 0.538). For Portland cement, d90 gave an even higher linear correlation for the initial setting time (r = 0.804) and the final setting time (r = 0.873) and exhibited a strong negative linear correlation for cumulative heat release (r = 0.901). Smaller particle sizes result in faster setting times, with d90 (the largest particles) being most closely correlated with the setting times of the samples. Copyright © 2015 American Association of Endodontists. All rights reserved.

  13. AP diameter shows the strongest correlation with CTDI and DLP in abdominal and chest CT.

    LENUS (Irish Health Repository)

    Zarb, Francis

    2010-01-01

    The purpose of this study is to investigate the relationships among cross-sectional diameters, weight and computed tomography (CT) dose descriptors (CTDI and DLP) to identify which is best used as a measure for the establishment of DRLs in CT. Data (gender, weight, cross-sectional diameters, dose descriptors) from 56 adult patients attending for either a CT examination of the abdomen or chest was obtained from two spiral CT units using automatic milliampere modulation. The AP diameter was demonstrated as the main contributing factor influencing the dose in CT (CTDI: r(2) = 0.269, p-value < or =0.001; DLP: r(2) = 0.260, p-value < or =0.001) since it has a greater correlation with radiation dose than body weight and can thus be its substitute in dose-reduction strategies and establishment of DRLs. The advantages of using the AP diameter are that it can easily be measured prior to scanning or retrospectively from previous CT images. However, further studies on the practicality of this approach are recommended.

  14. [FHF]−—The Strongest Hydrogen Bond under the Influence of External Interactions

    Directory of Open Access Journals (Sweden)

    Sławomir J. Grabowski

    2015-12-01

    Full Text Available A search through the Cambridge Structural Database (CSD for crystal structures containing the [FHF]− anion was carried out. Forty five hydrogen bifluoride structures were found mainly with the H-atom moved from the mid-point of the F…F distance. However several [FHF]− systems characterized by D∞h symmetry were found, the same as this anion possesses in the gas phase. The analysis of CSD results as well as the analysis of results of ab initio calculations on the complexes of [FHF]− with Lewis acid moieties show that the movement of the H-atom from the central position depends on the strength of interaction of this anion with external species. The analysis of the electron charge density distribution in complexes of [FHF]− was performed with the use of the Quantum Theory of Atoms in Molecules (QTAIM approach and the Natural Bond Orbitals (NBO method.

  15. Comparative study of the hemolytic and cytotoxic activities of nematocyst venoms from the jellyfish Cyanea nozakii Kishinouye and Nemopilema nomurai Kishinouye

    Science.gov (United States)

    Pang, Min; Xu, Jintao; Liu, Yunlong; Zhang, Xuelei

    2017-10-01

    Two species of jellyfish, Cyanea nozakii Kishinouye and Nemopilema nomurai Kishinouye, have occurred off coastal areas of the northeastern China Sea, Yellow Sea, and Bohai Sea in recent years. They influence marine ecosystem safety and fishery production, and also pose a risk to human health. The current study examined the hemolytic and cytotoxic activities of crude venoms extracted from the nematocysts of C. nozakii and N. nomurai. The results showed that there were more nematocysts on tentacles from C. nozakii than on tentacles of the same length from N. nomurai. The protein concentration per nematocyst extracted from N. nomurai was higher than that from C. nozakii. Both nematocyst venoms showed dose- and time-dependent hemolytic activity on erythrocytes from chicken, pigeon, and sheep, with sheep erythrocytes being the most sensitive, with EC50 values of 69.69 and 63.62 μg/mL over a 30-min exposure with N. nomurai and C. nozakii nematocyst venoms, respectively. A cytotoxic assay of both jellyfish venoms on A431 human epidermal carcinoma cells resulted in IC50 values of 68.6 and 40.9 μg/mL after 24-h incubation, respectively, with venom from C. nozakii showing stronger cytotoxic activity than that from N. nomurai. The results of current study indicate that nematocyst venom from C. nozakii had stronger hemolytic and cytotoxic activities than that from N. nomurai and, thus, C. nozakii might be more harmful to the health of humans and other species than are N. nomurai when they appear in coastal waters.

  16. Weight training, aerobic physical activities, and long-term waist circumference change in men.

    Science.gov (United States)

    Mekary, Rania A; Grøntved, Anders; Despres, Jean-Pierre; De Moura, Leandro Pereira; Asgarzadeh, Morteza; Willett, Walter C; Rimm, Eric B; Giovannucci, Edward; Hu, Frank B

    2015-02-01

    Findings on weight training and waist circumference (WC) change are controversial. This study examined prospectively whether weight training, moderate to vigorous aerobic activity (MVAA), and replacement of one activity for another were associated with favorable changes in WC and body weight (BW). Physical activity, WC, and BW were reported in 1996 and 2008 in a cohort of 10,500 healthy U.S. men in the Health Professionals Follow-up Study. Multiple linear regression models (partition/substitution) to assess these associations were used. After adjusting for potential confounders, a significant inverse dose-response relationship between weight training and WC change (P-trend weight training (-0.67 cm, 95% CI -0.93, -0.41) than for MVAA (-0.33 cm, 95% CI -0.40, -0.27), other activities (-0.16 cm, 95% CI -0.28, -0.03), or TV watching (0.08 cm, 95% CI 0.05, 0.12). Substituting 20 min/day of weight training for any other discretionary activity had the strongest inverse association with WC change. MVAA had the strongest inverse association with BW change (-0.23 kg, 95% CI -0.29, -0.17). Among various activities, weight training had the strongest association with less WC increase. Studies on frequency/volume of weight training and WC change are warranted. © 2014 The Obesity Society.

  17. Antibacterial assay-guided isolation of active compounds from Artocarpus heterophyllus heartwoods.

    Science.gov (United States)

    Septama, Abdi Wira; Panichayupakaranant, Pharkphoom

    2015-01-01

    Preparations from Artocarpus heterophyllus Lam. (Moraceae) heartwoods are used in the traditional folk medicine for the treatment of inflammation, malarial fever, and to prevent bacterial and fungal infections. The objective of this study was to isolate pure antibacterial compounds from A. heterophyllus heartwoods. The dried and powdered A. heterophyllus heartwoods were successively extracted with the following solvents: hexane, ethyl acetate, and methanol. Each of the extracts was screened for their antibacterial activities using a disc diffusion method (10 mg/disc). Their minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined using a broth microdilution method. The extract that showed the strongest antibacterial activities was fractionated to isolate the active compounds by an antibacterial assay-guided isolation process. The ethyl acetate extract exhibited the strongest antibacterial activities against Streptococcus mutans, S. pyogenes, and Bacillus subtilis with MIC values of 78, 39, and 9.8 µg/mL, respectively. Based on an antibacterial assay-guided isolation, four antibacterial compounds: cycloartocarpin (1), artocarpin (2), artocarpanone (3), and cyanomaclurin (4) were purified. Among these isolated compounds, artocarpin exhibited the strongest antibacterial activity against Gram-positive bacteria, including S. mutans, S. pyogenes, B. subtilis, Staphylococcus aureus, and S. epidermidis with MICs of 4.4, 4.4, 17.8, 8.9, and 8.9 µM, respectively, and MBCs of 8.9, 8.9, 17.8, 8.9, and 8.9 µM, respectively, while artocarpanone showed the strongest activity against Escherichia coli, a Gram-negative bacteria with MIC and MBC values of 12.9 and 25.8 µM, respectively. Only artocarpin showed inhibitory activity against Pseudomonas aeruginosa with an MIC of 286.4 µM.

  18. Potent Antifouling Marine Dihydroquinolin-2(1H)-one-Containing Alkaloids from the Gorgonian Coral-Derived Fungus Scopulariopsis sp.

    KAUST Repository

    Shao, Chang Lun

    2015-04-02

    Marine biofouling has a major economic impact, especially when it occurs on ship hulls or aquaculture facilities. Since the International Maritime Organization (IMO) treaty to ban the application of organotin-based paints to ships went into effect in 2008, there is an urgent demand for the development of efficient and environmentally friendly antifouling agents. Marine microorganisms have proved to be a potential source of antifouling natural compounds. In this study, six dihydroquinolin-2-one-containing alkaloids, three monoterpenoids combined with a 4-phenyl-3,4-dihydroquinolin-2(1H)-one (1–3) and three 4-phenyl-3,4-dihydroquinolin-2(1H)-one alkaloids (4–6), were isolated from the gorgonian coral-derived fungus Scopulariopsis sp. collected in the South China Sea. These dihydroquinolin-2-one-containing alkaloids were evaluated against the larval settlement of barnacle Balanus amphitrite, and antifouling activity was detected for the first time for this class of metabolites. All of them except 6 showed strong antifouling activity. Compounds 1 and 2 were discovered to be the most promising non-toxic antilarval settlement candidates. Especially, compound 1 is the strongest antifouling compound in nature until now which showed highly potent activity with picomolar level (EC50 17.5 pM) and a very safety and high therapeutic ratio (LC50/EC50 1200). This represents an effective non-toxic, anti-larval settlement structural class of promising antifouling lead compound. © 2015 Springer Science+Business Media New York

  19. The natural scorpion peptide, BmK NT1 activates voltage-gated sodium channels and produces neurotoxicity in primary cultured cerebellar granule cells.

    Science.gov (United States)

    Zou, Xiaohan; He, Yuwei; Qiao, Jinping; Zhang, Chunlei; Cao, Zhengyu

    2016-01-01

    The scorpion Buthus martensii Karsch has been used in Traditional Chinese Medicine to treat neuronal diseases such as neuropathic pain, paralysis and epilepsy for thousands of years. Studies have demonstrated that scorpion venom is the primary active component. Although scorpion venom can effectively attenuate pain in the clinic, it also produces neurotoxic response. In this study, toxicity guided purification led to identify a mammalian toxin termed BmK NT1 comprising of 65 amino acid residues and an amidated C-terminus, a mature peptide encoded by the nucleotide sequence (GenBank No. AF464898). In contract to the recombinant product of the same nucleotide sequence, BmK AGAP, which displayed analgesic and anti-tumor effect, intravenous injection (i.v.) of BmK NT1 produced acute toxicity in mice with an LD50 value of 1.36 mg/kg. In primary cultured cerebellar granule cells, BmK NT1 produced a concentration-dependent cell death with an IC50 value of 0.65 μM (0.41-1.03 μM, 95% Confidence Intervals, 95% CI) which was abolished by TTX, a voltage-gated sodium channel (VGSC) blocker. We also demonstrated that BmK NT1 produced modest sodium influx in cerebellar granule cell cultures with an EC50 value of 2.19 μM (0.76-6.40 μM, 95% CI), an effect similar to VGSC agonist, veratridine. The sodium influx response was abolished by TTX suggesting that BmK NT1-induced sodium influx is solely through activation of VGSC. Considered these data together, we demonstrated that BmK NT1 activated VGSC and produced neurotoxicity in cerebellar granule cell cultures. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Z-505 hydrochloride, an orally active ghrelin agonist, attenuates the progression of cancer cachexia via anabolic hormones in Colon 26 tumor-bearing mice.

    Science.gov (United States)

    Yoshimura, Makoto; Shiomi, Yoshihiro; Ohira, Yuta; Takei, Mineo; Tanaka, Takao

    2017-09-15

    Cancer cachexia is a progressive wasting syndrome characterized by anorexia and weight loss, specifically muscle wasting and fat depletion. There is no therapeutic agent for treatment of this syndrome. We investigated the anti-cachexia effects of Z-505 hydrochloride (Z-505), a new oral growth hormone secretagogue receptor 1a (GHSR1a) agonist, using a mouse model of cancer cachexia. We performed a calcium flux assay in Chinese hamster ovary (CHO-K1) cells stably expressing human GHSR1a to quantify the agonistic activity of Z-505. In Colon 26 tumor-bearing mice, Z-505 (300mg/kg, p.o., twice daily) was administered for 7 days to assess its anti-cachexia effects. Body weight and food intake were monitored during the period, and the skeletal muscle and epididymal fat weights were measured. Serum levels of insulin, insulin-like growth factor 1 (IGF-1), interleukin-6 (IL-6), and corticosterone were measured to confirm the mechanism of the anti-cachexia action of Z-505. Z-505 showed strong agonistic activity similar to that of human ghrelin, with a half maximal effective concentration (EC 50 ) value of 0.45nM. Z-505 treatment significantly increased food intake and inhibited the progression of weight loss. Z-505 also significantly attenuated muscle wasting and fat loss, and increased circulating levels of anabolic factors such as insulin and IGF-1, but not catabolic factors such as IL-6 and corticosterone. These findings suggest that Z-505 might be effective in the treatment of cachexia via the increased anabolic hormone levels stimulated by the activation of the ghrelin receptor, GHSR1a. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Nanomolar bifenthrin alters synchronous Ca2+ oscillations and cortical neuron development independent of sodium channel activity.

    Science.gov (United States)

    Cao, Zhengyu; Cui, Yanjun; Nguyen, Hai M; Jenkins, David Paul; Wulff, Heike; Pessah, Isaac N

    2014-04-01

    Bifenthrin, a relatively stable type I pyrethroid that causes tremors and impairs motor activity in rodents, is broadly used. We investigated whether nanomolar bifenthrin alters synchronous Ca(2+) oscillations (SCOs) necessary for activity-dependent dendritic development. Primary mouse cortical neurons were cultured 8 or 9 days in vitro (DIV), loaded with the Ca(2+) indicator Fluo-4, and imaged using a Fluorescence Imaging Plate Reader Tetra. Acute exposure to bifenthrin rapidly increased the frequency of SCOs by 2.7-fold (EC50 = 58 nM) and decreased SCO amplitude by 36%. Changes in SCO properties were independent of modifications in voltage-gated sodium channels since 100 nM bifenthrin had no effect on the whole-cell Na(+) current, nor did it influence neuronal resting membrane potential. The L-type Ca(2+) channel blocker nifedipine failed to ameliorate bifenthrin-triggered SCO activity. By contrast, the metabotropic glutamate receptor (mGluR)5 antagonist MPEP [2-methyl-6-(phenylethynyl)pyridine] normalized bifenthrin-triggered increase in SCO frequency without altering baseline SCO activity, indicating that bifenthrin amplifies mGluR5 signaling independent of Na(+) channel modification. Competitive [AP-5; (-)-2-amino-5-phosphonopentanoic acid] and noncompetitive (dizocilpine, or MK-801 [(5S,10R)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate]) N-methyl-d-aspartate antagonists partially decreased both basal and bifenthrin-triggered SCO frequency increase. Bifenthrin-modified SCO rapidly enhanced the phosphorylation of cAMP response element-binding protein (CREB). Subacute (48 hours) exposure to bifenthrin commencing 2 DIV-enhanced neurite outgrowth and persistently increased SCO frequency and reduced SCO amplitude. Bifenthrin-stimulated neurite outgrowth and CREB phosphorylation were dependent on mGluR5 activity since MPEP normalized both responses. Collectively these data identify a new mechanism by which bifenthrin potently alters Ca(2

  2. Receptor activity modifying proteins (RAMPs) interact with the VPAC1 receptor: evidence for differential RAMP modulation of multiple signalling pathways

    International Nuclear Information System (INIS)

    Christopoulos, G.; Morfis, M.; Sexton, P.M.; Christopoulos, A.; Laburthe, M.; Couvineau, A.

    2001-01-01

    Full text: Receptor activity modifying proteins (RAMP) constitute a family of three accessory proteins that affect the expression and/or phenotype of the calcitonin receptor (CTR) or CTR-like receptor (CRLR). In this study we screened a range of class II G protein-coupled receptors (PTH1, PTH2, GHRH, VPAC1, VPAC2 receptors) for possible RAMP interactions by measurement of receptor-induced translocation of c-myc tagged RAMP1 or HA tagged RAMP3. Of these, only the VPAC1 receptor caused significant translocation of c-myc-RAMP1 or HA-RAMP3 to the cell surface. Co-transfection of VPAC1 and RAMPs did not alter 125 I-VIP binding and specificity. VPAC1 receptor function was subsequently analyzed through parallel determinations of cAMP accumulation and phosphoinositide (PI) hydrolysis in the presence and absence of each of the three RAMPs. In contrast to CTR-RAMP interaction, where there was an increase in cAMP Pharmacologisand a decrease in PI hydrolysis, VPAC1-RAMP interaction was characterized by a specific increase in agonist-mediated PI hydrolysis when co-transfected with RAMP2. This change was due to an enhancement of Emax with no change in EC 50 value for VIP. No significant change in cAMP accumulation was observed. This is the first demonstration of an interaction of RAMPs with a G protein-coupled receptor outside the CTR family and may suggest a more generalized role for RAMPs in modulating G protein-coupled receptor signaling. Copyright (2001) Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists

  3. EL4 cell-based colorimetric toxin neutralization activity assays for determination of neutralizing anti-ricin antibodies.

    Science.gov (United States)

    Lindsey, Changhong Y; Brown, J Edward; Torabazar, Nahid R; Smith, Leonard A

    2013-01-01

    A recombinant ricin toxin A-chain 1-33/44-198 vaccine (RVEc), developed at the United States Army Medical Research Institute of Infectious Diseases as a vaccine candidate, is under investigation in a phase 1 clinical study. To effectively evaluate the immunogenicity of this ricin vaccine and to eliminate the use of radioactive material, an EL4 cell-based colorimetric toxin neutralization activity (TNA) assay using a CellTiter 96 AQueous One Solution Cell Proliferation Assay Reagent has been developed, optimized, and applied in the vaccine efficacy studies. The TNA assay measures the protective neutralizing anti-ricin antibodies in animal sera by determining the cell viability after ricin exposure in the assay system and comparing it to a purified mouse polyclonal antiricin IgG standard curve. The standard curve of the anti-ricin TNA assay closely fits a four-parameter logistic regression model. The unknown test sample concentration was expressed as microg/mL, but not the 50% effective concentration (EC50), which was determined by most TNA assays. The neutralizing endpoint titers, not the 50% effective dilution (ED50), of human specimens were measured with the TNA assay in support of the clinical study of the RVEc vaccine. The optimal amount of ricin toxin, EL4 cells, and concentration of standards used in the assay system was established to minimize false-negative and false-positive results of serum specimens from the nonclinical and clinical studies of RVEc. The testing conditions were adjusted to optimize assay performance. The colorimetric TNA assay replaced a radioactive TNA assay previously used in the ricin vaccine studies.

  4. Efficient modulation of γ-aminobutyric acid type A receptors by piperine derivatives.

    Science.gov (United States)

    Schöffmann, Angela; Wimmer, Laurin; Goldmann, Daria; Khom, Sophia; Hintersteiner, Juliane; Baburin, Igor; Schwarz, Thomas; Hintersteininger, Michael; Pakfeifer, Peter; Oufir, Mouhssin; Hamburger, Matthias; Erker, Thomas; Ecker, Gerhard F; Mihovilovic, Marko D; Hering, Steffen

    2014-07-10

    Piperine activates TRPV1 (transient receptor potential vanilloid type 1 receptor) receptors and modulates γ-aminobutyric acid type A receptors (GABAAR). We have synthesized a library of 76 piperine analogues and analyzed their effects on GABAAR by means of a two-microelectrode voltage-clamp technique. GABAAR were expressed in Xenopus laevis oocytes. Structure-activity relationships (SARs) were established to identify structural elements essential for efficiency and potency. Efficiency of piperine derivatives was significantly increased by exchanging the piperidine moiety with either N,N-dipropyl, N,N-diisopropyl, N,N-dibutyl, p-methylpiperidine, or N,N-bis(trifluoroethyl) groups. Potency was enhanced by replacing the piperidine moiety by N,N-dibutyl, N,N-diisobutyl, or N,N-bistrifluoroethyl groups. Linker modifications did not substantially enhance the effect on GABAAR. Compound 23 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dipropyl-2,4-pentadienamide] induced the strongest modulation of GABAA (maximal GABA-induced chloride current modulation (IGABA-max = 1673% ± 146%, EC50 = 51.7 ± 9.5 μM), while 25 [(2E,4E)-5-(1,3-benzodioxol-5-yl)-N,N-dibutyl-2,4-pentadienamide] displayed the highest potency (EC50 = 13.8 ± 1.8 μM, IGABA-max = 760% ± 47%). Compound 23 induced significantly stronger anxiolysis in mice than piperine and thus may serve as a starting point for developing novel GABAAR modulators.

  5. Characterization of a Novel 99mTc-Carbonyl Complex as a Functional Probe of MDR1 P-Glycoprotein Transport Activity

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    Mary Dyszlewski

    2002-01-01

    Full Text Available Multidrug resistance (MDR mediated by overexpression of MDR1 P-glycoprotein (Pgp is one of the best characterized barriers to chemotherapy in cancer patients. Furthermore, the protective function of Pgp-mediated efflux of xenobiotics in various organs has a profound effect on the bioavailability of drugs in general. Thus, there is an expanding requirement to noninvasively interrogate Pgp transport activity in vivo. We herein report the Pgp recognition properties of a novel 99mTc(I-tricarbonyl complex, [99mTc(CO3(MIBI3] + (Tc-CO-MIBI. Tc-CO-MIBI showed 60-fold higher accumulation in drug-sensitive KB 3–1 cells compared to colchicine-selected drug-resistant KB 8-5 cells. In KB 8-5 cells, tracer enhancement was observed with the potent MDR modulator LY335979 (EC50 = 62 nM. Similar behavior was observed using drug-sensitive MCF-7 breast adenocarcinoma cells and MCF-7/MDR1 stable transfectants, confirming that Tc-CO-MIBI is specifically excluded by overexpression of MDR1 Pgp. By comparison, net accumulation in control H69 lung tumor cells was 9-fold higher than in MDR-associated protein (MRP1-expressing H69AR cells, indicating only modest transport by MRP1. Biodistribution analysis following tail vein injection of Tc-CO-MIBI showed delayed liver clearance as well as enhanced brain uptake and retention in mdr1a/1b(−/− gene deleted mice versus wild-type mice, directly demonstrating that Tc-CO-MIBI is a functional probe of Pgp transport activity in vivo.

  6. Antipsychotic activity of standardized Bacopa extract against ketamine-induced experimental psychosis in mice: Evidence for the involvement of dopaminergic, serotonergic, and cholinergic systems.

    Science.gov (United States)

    Chatterjee, Manavi; Verma, Rajkumar; Kumari, Reena; Singh, Seema; Verma, Anil Kumar; Dwivedi, Anil Kumar; Palit, Gautam

    2015-01-01

    Schizophrenia is a chronic disabling psychiatric disorder affecting 1% of the population worldwide. Due to the adverse effects of available antipsychotic medications, recent investigations have focused on the search for well-tolerated, safe molecules from natural resources to control the severity and progression of schizophrenia. To screen the standardized extract of Bacopa monniera Linn. (Scrophulariaceae) (BM) for its antipsychotic potential in the ketamine-induced psychosis model with mice. Graded dose of BM (40, 80, and 120 mg/kg, p.o.) were given to the mice 1 h prior to ketamine administration and tested for positive symptoms and cognitive deficits. A chronic ketamine treatment regimen was used to study the effect of BM on negative symptoms such as immobility enhancement. Each mouse was used once for the behavioral studies. BM reduced ketamine-induced hyperactivity with an EC50 value of 76.60 mg/kg. The 80 mg/kg dose was used for all other behavior analysis. Pretreatment with BM at 80 mg/kg showed two-fold increases in transfer latency time (TLT) in passive avoidance task. Chronic BM pretreatment (80 mg/kg p.o. daily × 10 d) ameliorated the ketamine-induced enhanced immobility effect by 21% in the forced swim test. BM treatment reversed ketamine-induced increase in monoamine oxidase activity in both cortex and striatum and normalized the acetylcholinesterase activity and the glutamate levels in the hippocampus. Overall our findings suggest that BM possesses antipsychotic properties which might be due to its modulatory action on dopamine, serotonin, and glutamate neurotransmission.

  7. Antimicrobial activities of some Thai traditional medical longevity formulations from plants and antibacterial compounds from Ficus foveolata.

    Science.gov (United States)

    Meerungrueang, W; Panichayupakaranant, P

    2014-09-01

    Medicinal plants involved in traditional Thai longevity formulations are potential sources of antimicrobial compounds. To evaluate the antimicrobial activities of some extracts from medicinal plants used in traditional Thai longevity formulations against some oral pathogens, including Streptococcus pyogenes, Streptococcus mitis, Streptococcus mutans, and Candida albicans. An extract that possessed the strongest antimicrobial activity was fractionated to isolate and identify the active compounds. Methanol and ethyl acetate extracts of 25 medicinal plants used as Thai longevity formulations were evaluated for their antimicrobial activity using disc diffusion (5 mg/disc) and broth microdilution (1.2-2500 µg/mL) methods. The ethyl acetate extract of Ficus foveolata Wall. (Moraceae) stems that exhibited the strongest antibacterial activity was fractionated to isolate the active compounds by an antibacterial assay-guided isolation process. The ethyl acetate extract of F. foveolata showed the strongest antibacterial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 19.5-39.0 and 39.0-156.2 µg/mL, respectively. On the basis of an antibacterial assay-guided isolation, seven antibacterial compounds, including 2,6-dimethoxy-1,4-benzoquinone (1), syringaldehyde (2), sinapaldehyde (3), coniferaldehyde (4), 3β-hydroxystigmast-5-en-7-one (5), umbelliferone (6), and scopoletin (7), were purified. Among these isolated compounds, 2,6-dimethoxy-1,4-benzoquinone (1) exhibited the strongest antibacterial activities against S. pyogenes, S. mitis, and S. mutans with MIC values of 7.8, 7.8, and 15.6 µg/mL, and MBC values of 7.8, 7.8, and 31.2 µg/mL, respectively. In addition, this is the first report of these antibacterial compounds in the stems of F. foveolata.

  8. Simultaneous quantification of ten constituents of Xanthoceras sorbifolia Bunge using UHPLC-MS methods and evaluation of their radical scavenging, DNA scission protective, and α-glucosidase inhibitory activities.

    Science.gov (United States)

    Zhang, Yu; Ma, Jian-Nan; Ma, Chun-Li; Qi, Zhi; Ma, Chao-Mei

    2015-11-01

    The present study was designed to investigate the bioactive constituents of Xanthoceras sorbifolia in terms of amounts and their antioxidant, DNA scission protection, and α-glucosidase inhibitory activities. Simultaneous quantification of 10 X. sorbifolia constituents was carried out by a newly established ultra-high performance liquid chromatography-quadrupole mass spectrometry method (UHPLC-MS). The antioxidant activities were evaluated by measuring DPPH radical scavenging and DNA scission protective activities. The α-glucosidase inhibitory activities were investigated by using an assay with α-glucosidase from Bacillus Stearothermophilus and disaccharidases from mouse intestine. We found that the wood of X. sorbifolia was rich in phenolic compounds with the contents of catechin, epicatechin, myricetin, and dihydromyricetin being 0.12-0.19, 1.94-2.16, 0.77-0.91, and 6.76-7.89 mg·g(-1), respectively. The four constituents strongly scavenged DPPH radicals (with EC50 being 4.2, 3.8 and 5.7 μg·mL(-1), respectively) and remarkably protected peroxyl radical-induced DNA strand scission (92.10%, 94.66%, 75.44% and 89.95% of protection, respectively, at a concentration of 10 μmol·L(-1)). A dimeric flavan 3-ol, epigallocatechin-(4β→8, 2β→O-7)-epicatechin potently inhibited α-glucosidase with an IC50 value being as low as 1.2 μg·mL(-1). The established UHPLC-MS method could serve as a quality control tool for X. sorbifolia. In conclusion, the high contents of antioxidant and α-glucosidase inhibitory constituents in X. sorbifolia support its use as complementation of other therapeutic agents for metabolic disorders, such as diabetes and hypertension. Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  9. Composition, antimicrobial, antioxidant, and antiproliferative activity of Origanum dictamnus (dittany essential oil

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    Gregoria Mitropoulou

    2015-05-01

    essential oil was 0.045±0.0042% (v/v and was mainly attributed to carvacrol. The EC50 value for the essential oil in the 72h SRB assay in HepG2 cells was estimated to be 0.0069±0.00014% (v/v. Among the individual constituents tested, carvacrol was the most bioactive compound and accounted for the observed antiproliferative activity of the essential oil. Conclusions: The results revealed that O. dictamnus essential oil is a noteworthy growth inhibitor against the microbes studied. It also possesses significant antioxidant activity and demonstrated excellent cytotoxicity against HepG2 cells. Taken together, O. dictamnus essential oil may represent an effective and inexpensive source of potent natural antimicrobial agents with health-promoting properties, which may be incorporated in food systems.

  10. Composition, antimicrobial, antioxidant, and antiproliferative activity of Origanum dictamnus (dittany) essential oil.

    Science.gov (United States)

    Mitropoulou, Gregoria; Fitsiou, Eleni; Stavropoulou, Elisavet; Papavassilopoulou, Eleni; Vamvakias, Manolis; Pappa, Aglaia; Oreopoulou, Antigoni; Kourkoutas, Yiannis

    2015-01-01

    attributed to carvacrol. The EC50 value for the essential oil in the 72h SRB assay in HepG2 cells was estimated to be 0.0069±0.00014% (v/v). Among the individual constituents tested, carvacrol was the most bioactive compound and accounted for the observed antiproliferative activity of the essential oil. The results revealed that O. dictamnus essential oil is a noteworthy growth inhibitor against the microbes studied. It also possesses significant antioxidant activity and demonstrated excellent cytotoxicity against HepG2 cells. Taken together, O. dictamnus essential oil may represent an effective and inexpensive source of potent natural antimicrobial agents with health-promoting properties, which may be incorporated in food systems.

  11. Evaluation of the anthelmintic activity and toxicity of an aqueous extract of Chenopodium ambrosioides in goats

    Directory of Open Access Journals (Sweden)

    Gisele Dias da Silva

    2016-10-01

    Full Text Available ABSTRACT. da Silva G.D., Botura M.B., de Lima H.G., de Oliveira J.V.A., Moreira E.L.T., Santos F.O., de Souza T.S., de Almeida M.A.O. & Batatinha M.J.M. Evaluation of the anthelmintic activity and toxicity of an aqueous extract of Chenopodium ambrosioides in goats. [Avaliação da atividade anti-helmíntica e toxicidade do extrato aquoso de Chenopodium ambrosioides em caprinos.] Revista Brasileira de Medicina Veterinária, 38(Supl.1:156-162, 2016. Programa de Pós-Graduação em Ci- ência Animal nos Trópicos, Universidade Federal da Bahia, Av. Ademar de Barros, 500, Ondina, Salvador, BA 40170-110, Brasil. E-mail: mjmb@ufba.br The objective of this study was to evaluate the anthelmintic activity of an aqueous extract (AE from Chenopodium ambrosioides on goat gastrointestinal nematodes (GINs and its toxic effects. The anthelmintic activity in vitro was investigated using the inhibition of egg hatching assay (EHA, while cytotoxicity on Vero cells was evaluated using the MTT test. In vivo, thirty goats that were naturally infected with GINs were divided into three groups: group I, treated with a daily dose of AE C. ambrosioides (700mg/kg for eight days; group II (positive control, treated with a single dose of levamisole phosphate (6.3mg/kg; and Group III, untreated (negative control. Treatment efficacy was assessed on the basis of egg counts (FEC, faecal cultures and post-mortem worm burden counts. Clinical and laboratory evaluations were performed to detect toxic effects associated with treatment. In the EHA, the EC50 and EC90 corresponded to 1.6 and 1.9mg/mL, respectively. The AE promoted a slight reduction in cell viability in the cytotoxicity test. The AE reduced (p <0.05 the number of infective larvae of the genera Haemonchus and Oesophagostomum. The anthelmintic treatment of goats with AE C.ambrosioides resulted in moderate efficacy against infective larvae, but revealed neither ovicidal nor toxic activity towards adult nematodes. No toxic

  12. Alkaloids from Prosopis juliflora leaves induce glial activation, cytotoxicity and stimulate NO production.

    Science.gov (United States)

    Silva, A M M; Silva, A R; Pinheiro, A M; Freitas, S R V B; Silva, V D A; Souza, C S; Hughes, J B; El-Bachá, R S; Costa, M F D; Velozo, E S; Tardy, M; Costa, S L

    2007-04-01

    Prosopis juliflora is used for feeding cattle and humans. Intoxication with the plant has been reported, and is characterized by neuromuscular alterations and gliosis. Total alkaloidal extract (TAE) was obtained using acid/basic-modified extraction and was fractionated. TAE and seven alkaloidal fractions, at concentrations ranging 0.03-30 microg/ml, were tested for 24h on astrocyte primary cultures derived from the cortex of newborn Wistar rats. The MTT test and the measure of LDH activity on the culture medium, revealed that TAE and fractions F29/30, F31/33, F32 and F34/35 were cytotoxic to astrocytes. The EC(50) values for the most toxic compounds, TAE, F31/33 and F32 were 2.87 2.82 and 3.01 microg/ml, respectively. Morphological changes and glial cells activation were investigated through Rosenfeld's staining, by immunocytochemistry for the protein OX-42, specific of activated microglia, by immunocytochemistry and western immunoblot for GFAP, the marker of reactive and mature astrocytes, and by the production of nitric oxide (NO). We observed that astrocytes exposed to 3 microg/ml TAE, F29/30 or F31/33 developed compact cell body with many processes overexpressing GFAP. Treatment with 30 microg/ml TAE and fractions, induced cytotoxicity characterized by a strong cell body contraction, very thin and long processes and condensed chromatin. We also observed that when compared with the control (+/-1.34%), the proportion of OX-42 positive cells was increased in cultures treated with 30 microg/ml TAE or F29/30, F31/33, F32 and F34/35, with values raging from 7.27% to 28.74%. Moreover, incubation with 3 microg/ml F32, 30 microg/ml TAE, F29/30, F31/33 or F34/35 induced accumulation of nitrite in culture medium indicating induction of NO production. Taken together these results show that TAE and fractionated alkaloids from P. juliflora act directly on glial cells, inducing activation and/or cytotoxicity, stimulating NO production, and may have an impact on neuronal

  13. Antioxidant activities of Physalis peruviana.

    Science.gov (United States)

    Wu, Sue-Jing; Ng, Lean-Teik; Huang, Yuan-Man; Lin, Doung-Liang; Wang, Shyh-Shyan; Huang, Shan-Ney; Lin, Chun-Ching

    2005-06-01

    Physalis peruviana (PP) is a widely used medicinal herb for treating cancer, malaria, asthma, hepatitis, dermatitis and rheumatism. In this study, the hot water extract (HWEPP) and extracts prepared from different concentrations of ethanol (20, 40, 60, 80 and 95% EtOH) from the whole plant were evaluated for antioxidant activities. Results displayed that at 100 mug/ml, the extract prepared from 95% EtOH exhibited the most potent inhibition rate (82.3%) on FeCl2-ascorbic acid induced lipid peroxidation in rat liver homogenate. At concentrations 10-100 microg/ml, this extract also demonstrated the strongest superoxide anion scavenging and inhibitory effect on xanthine oxidase activities. In general, the ethanol extracts revealed a stronger antioxidant activity than alpha-tocopherol and HWEPP. Compared to alpha-tocopherol, the IC50 value of 95% EtOH PP extract was lower in thiobarbituric acid test (IC50=23.74 microg/ml vs. 26.71 microg/ml), in cytochrome c test (IC50=10.40 microg/ml vs. 13.39 microg/ml) and in xanthine oxidase inhibition test (IC50=8.97 microg/ml vs. 20.68 microg/ml). The present study concludes that ethanol extracts of PP possess good antioxidant activities, and the highest antioxidant properties were obtained from the 95% EtOH PP.

  14. Leisure-time physical activity in relation to occupational physical activity among women.

    Science.gov (United States)

    Ekenga, Christine C; Parks, Christine G; Wilson, Lauren E; Sandler, Dale P

    2015-05-01

    The objective of this study is to examine the association between occupational physical activity and leisure-time physical activity among US women in the Sister Study. We conducted a cross-sectional study of 26,334 women who had been employed in their current job for at least 1 year at baseline (2004-2009). Occupational physical activity was self-reported and leisure-time physical activity was estimated in metabolic equivalent hours per week. Log multinomial regression was used to evaluate associations between occupational (sitting, standing, manually active) and leisure-time (insufficient, moderate, high) activity. Models were adjusted for age, race/ethnicity, education, income, geographic region, and body mass index. Only 54% of women met or exceeded minimum recommended levels of leisure-time physical activity (moderate 32% and high 22%). Women who reported sitting (prevalence ratio (PR)=0.82, 95% confidence interval (CI): 0.74-0.92) or standing (PR=0.84, 95% CI: 0.75-0.94) most of the time at work were less likely to meet the requirements for high leisure-time physical activity than manually active workers. Associations were strongest among women living in the Northeast and the South. In this nationwide study, low occupational activity was associated with lower leisure-time physical activity. Women who are not active in the workplace may benefit from strategies to promote leisure-time physical activity. Published by Elsevier Inc.

  15. Oviposition-stimulant and ovicidal activities of Moringa oleifera lectin on Aedes aegypti.

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    Nataly Diniz de Lima Santos

    Full Text Available Natural insecticides against the vector mosquito Aedes aegypti have been the object of research due to their high level of eco-safety. The water-soluble Moringa oleifera lectin (WSMoL is a larvicidal agent against A. aegypti. This work reports the effects of WSMoL on oviposition and egg hatching of A. aegypti.WSMoL crude preparations (seed extract and 0-60 protein fraction, at 0.1 mg/mL protein concentration, did not affect oviposition, while A. aegypti gravid females laid their eggs preferentially (73% in vessels containing isolated WSMoL (0.1 mg/mL, compared with vessels containing only distilled water (control. Volatile compounds were not detected in WSMoL preparation. The hatchability of fresh eggs deposited in the solutions in the oviposition assay was evaluated. The numbers of hatched larvae in seed extract, 0-60 protein fraction and WSMoL were 45 ± 8.7 %, 20 ± 11 % and 55 ± 7.5 %, respectively, significantly (p<0.05 lower than in controls containing only distilled water (75-95%. Embryos were visualized inside fresh control eggs, but not within eggs that were laid and maintained in WSMoL solution. Ovicidal activity was also assessed using stored A. aegypti eggs. The protein concentrations able to reduce the hatching rate by 50% (EC50 were 0.32, 0.16 and 0.1 mg/mL for seed extract, 0-60 protein fraction and WSMoL, respectively. The absence of hatching of stored eggs treated with WSMoL at 0.3 mg/mL (EC99 after transfer to medium without lectin indicates that embryos within the eggs were killed by WSMoL. The reduction in hatching rate of A. aegypti was not linked to decrease in bacteria population.WSMoL acted both as a chemical stimulant cue for ovipositing females and ovicidal agent at a given concentration. The oviposition-stimulant and ovicidal activities, combined with the previously reported larvicidal activity, make WSMoL a very interesting candidate in integrated A. aegypti control.

  16. Antioxidant activity of hydroalcoholic leaf extracts of Psidium guajava and Persea Americana, an invitro study

    International Nuclear Information System (INIS)

    Kumar, Amith; Kumarachandra, Reshma; Rai, Rajalakshmi; Rao, Satish; Suchetha Kumari; Joshi, Manjunath

    2013-01-01

    Ionizing radiation produce deleterious effects in the living organisms. Rapid technological advancement has increased human exposure to ionizing radiations enormously. Several plants have been screened for their radio protective ability and the hunt for identifying many more safe, nontoxic and effective ones is in progress. The aim of the present study was to evaluate the antioxidant activity in hydro alcoholic leaf extract of Psidium guajava (guava) and Persea americana (avocado). The antioxidant assay such as 2,2-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) free radical scavenging assay, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay, chelation of iron by plant extract, hydroxyl radical scavenging assay, ferric reducing antioxidant potential (FRAP), and total antioxidant activity of extract was analyzed using spectrophotometer. Phytochemical screening and HPLC analysis of leaf extracts were also performed. The results indicated that the IC50 value of hydro alcoholic leaf extract of P.guajava and P. americana were 14 μg/ml and 15 μg/ml in ABTS free radical scavenging assay, 4 μg/ml and 2.5 μg/ml in DPPH free radical scavenging assay, 7.2 μg/ml and 8.4 μg/ml in chelation of iron by plant extract, 2 μg/ml and, 4.3 μg/ml in hydroxyl radical scavenging assay and effective concentration(EC50) was 57.80 μg/ml and 87.56 μg/ml in FRAP assay respectively. The results for total antioxidant activity indicated that 242.3 μg/ml of P.guajava and 432.7 μg/ml of P.americana extract was equivalent to 100 μg/ml of standard qurecetin respectively. Qualitative analysis of hydroalcoholic leaf extracts revealed the presence of flavonoids, tannins, saponions, terpenoids, and glycosides. HPLC analysis confirmed the presence of flavonoids qurecetin and rutin in leaf extracts on comparison with standard compounds. Our study showed that hydro alcoholic leaf extracts of Psidium guajava and Persea americana act as strong antioxidant and free

  17. The role of supplemental ultraviolet-B radiation in altering the metabolite profile, essential oil content and composition, and free radical scavenging activities of Coleus forskohlii, an indigenous medicinal plant.

    Science.gov (United States)

    Takshak, Swabha; Agrawal, S B

    2016-04-01

    The effects of supplemental ultraviolet-B (s-UV-B; 3.6 kJ m(-2) day(-1) above ambient) radiation were investigated on plant metabolite profile, essential oil content and composition, and free radical scavenging capacities of methanolic extracts of Coleus forskohlii (an indigenous medicinal plant) grown under field conditions. Essential oil was isolated using hydrodistillation technique while alterations in metabolite profile and oil composition were determined via gas chromatography-mass spectroscopy (GC-MS). Leaf and root methanolic extracts were investigated via various in vitro assays for their DPPH radical-, superoxide radical-, hydrogen peroxide-, hydroxyl radical-, and nitric oxide radical scavenging activities, ferrous ion chelating activity, and reducing power. Phytochemical analysis revealed the presence of alkaloids, anthocyanins, coumarins, flavonoids, glycosides, phenols, saponins, steroids, tannins, and terpenoids. Oil content was found to be reduced (by ∼7 %) in supplemental UV-B (s-UV-B) treated plants; the composition of the plant extracts as well as essential oil was also considerably altered. Methanolic extracts from treated plant organs showed more potency as free radical scavengers (their EC50 values being lower than their respective controls). Anomalies were observed in Fe(2+) chelating activity for both leaves and roots. The present study concludes that s-UV-B adversely affects oil content in C. forskohlii and also alters the composition and contents of metabolites in both plant extracts and oil. The results also denote that s-UV-B treated plant organs might be more effective in safeguarding against oxidative stress, though further studies are required to authenticate these findings.

  18. Endothelial epithelial sodium channel inhibition activates endothelial nitric oxide synthase via phosphoinositide 3-kinase/Akt in small-diameter mesenteric arteries.

    Science.gov (United States)

    Pérez, Francisco R; Venegas, Fabiola; González, Magdalena; Andrés, Sergio; Vallejos, Catalina; Riquelme, Gloria; Sierralta, Jimena; Michea, Luis

    2009-06-01

    Recent studies have shown that the epithelial sodium channel (ENaC) is expressed in vascular tissue. However, the role that ENaC may play in the responses to vasoconstrictors and NO production has yet to be addressed. In this study, the contractile responses of perfused pressurized small-diameter rat mesenteric arteries to phenylephrine and serotonin were reduced by ENaC blockade with amiloride (75.1+/-3.2% and 16.9+/-2.3% of control values, respectively; P<0.01) that was dose dependent (EC(50)=88.9+/-1.6 nmol/L). Incubation with benzamil, another ENaC blocker, had similar effects. alpha, beta, and gamma ENaC were identified in small-diameter rat mesenteric arteries using RT-PCR and Western blot with specific antibodies. In situ hybridization and immunohistochemistry localized ENaC expression to the tunica media and endothelium of small-diameter rat mesenteric arteries. Patch-clamp experiments demonstrated that primary cultures of mesenteric artery endothelial cells expressed amiloride-sensitive sodium currents. Mechanical ablation of the endothelium or inhibition of eNOS with N(omega)-nitro-L-arginine inhibited the reduction in contractility caused by ENaC blockers. ENaC inhibitors increased eNOS phosphorylation (Ser 1177) and Akt phosphorylation (Ser 473). The presence of the phosphoinositide 3-kinase inhibitor LY294002 blunted Akt phosphorylation and eNOS phosphorylation and the decrease in the response to phenylephrine caused by blockers of ENaC, indicating that the phosphoinositide 3-kinase/Akt pathway was activated after ENaC inhibition. Finally, we observed that the effects of blockers of ENaC were flow dependent and that the vasodilatory response to shear stress was enhanced by ENaC blockade. Our results identify a previously unappreciated role for ENaC as a negative modulator of eNOS and NO production in resistance arteries.

  19. Detection of the antiviral activity of epicatechin isolated from Salacia crassifolia (Celastraceae) against Mayaro virus based on protein C homology modelling and virtual screening.

    Science.gov (United States)

    Ferreira, P G; Ferraz, A C; Figueiredo, J E; Lima, C F; Rodrigues, V G; Taranto, A G; Ferreira, J M S; Brandão, G C; Vieira-Filho, S A; Duarte, L P; de Brito Magalhães, C L; de Magalhães, J C

    2018-02-24

    Mayaro fever, caused by Mayaro virus (MAYV) is a sub-lethal disease with symptoms that are easily confused with those of dengue fever, except for polyarthralgia, which may culminate in physical incapacitation. Recently, outbreaks of MAYV have been documented in metropolitan areas, and to date, there is no therapy or vaccine available. Moreover, there is no information regarding the three-dimensional structure of the viral proteins of MAYV, which is important in the search for antivirals. In this work, we constructed a three-dimensional model of protein C of MAYV by homology modelling, and this was employed in a manner similar to that of receptors in virtual screening studies to evaluate 590 molecules as prospective antiviral agents. In vitro bioassays were utilized to confirm the potential antiviral activity of the flavonoid epicatechin isolated from Salacia crassifolia (Celastraceae). The virtual screening showed that six flavonoids were promising ligands for protein C. The bioassays showed potent antiviral action of epicatechin, which protected the cells from almost all of the effects of viral infection. An effective concentration (EC 50 ) of 0.247 μmol/mL was observed with a selectivity index (SI) of 7. The cytotoxicity assay showed that epicatechin has low toxicity, with a 50% cytotoxic concentration (CC 50 ) greater than 1.723 µmol/mL. Epicatechin was found to be twice as potent as the reference antiviral ribavirin. Furthermore, a replication kinetics assay showed a strong inhibitory effect of epicatechin on MAYV growth, with a reduction of at least four logs in virus production. Our results indicate that epicatechin is a promising candidate for further testing as an antiviral agent against Mayaro virus and other alphaviruses.

  20. Inhibition of TRPA1 channel activity in sensory neurons by the glial cell line-derived neurotrophic factor family member, artemin

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    Wang Shenglan

    2011-05-01

    Full Text Available Abstract Background The transient receptor potential (TRP channel subtype A1 (TRPA1 is known to be expressed on sensory neurons and respond to changes in temperature, pH and local application of certain noxious chemicals such as allyl isothiocyanate (AITC. Artemin is a neuronal survival and differentiation factor and belongs to the glial cell line-derived neurotrophic factor (GDNF family. Both TRPA1 and artemin have been reported to be involved in pathological pain initiation and maintenance. In the present study, using whole-cell patch clamp recording technique, in situ hybridization and behavioral analyses, we examined the functional interaction between TRPA1 and artemin. Results We found that 85.8 ± 1.9% of TRPA1-expressing neurons also expressed GDNF family receptor alpha 3 (GFR α3, and 87.5 ± 4.1% of GFRα3-expressing neurons were TRPA1-positive. In whole-cell patch clamp analysis, a short-term treatment of 100 ng/ml artemin significantly suppressed the AITC-induced TRPA1 currents. A concentration-response curve of AITC resulting from the effect of artemin showed that this inhibition did not change EC50 but did lower the AITC-induced maximum response. In addition, pre-treatment of artemin significantly suppressed the number of paw lifts induced by intraplantar injection of AITC, as well as the formalin-induced pain behaviors. Conclusions These findings that a short-term application of artemin inhibits the TRPA1 channel's activity and the sequential pain behaviors suggest a role of artemin in regulation of sensory neurons.

  1. Effects of Intermediates between Vitamins K2 and K3 on Mammalian DNA Polymerase Inhibition and Anti-Inflammatory Activity

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    Takeshi Azuma

    2011-02-01

    Full Text Available Previously, we reported that vitamin K3 (VK3, but not VK1 or VK2 (=MK-4, inhibits the activity of human DNA polymerase γ (pol γ. In this study, we chemically synthesized three intermediate compounds between VK2 and VK3, namely MK-3, MK-2 and MK-1, and investigated the inhibitory effects of all five compounds on the activity of mammalian pols. Among these compounds, MK-2 was the strongest inhibitor of mammalian pols α, κ and λ, which belong to the B, Y and X families of pols, respectively; whereas VK3 was the strongest inhibitor of human pol γ, an A-family pol. MK-2 potently inhibited the activity of all animal species of pol tested, and its inhibitory effect on pol λ activity was the strongest with an IC50 value of 24.6 μM. However, MK-2 did not affect the activity of plant or prokaryotic pols, or that of other DNA metabolic enzymes such as primase of pol α, RNA polymerase, polynucleotide kinase or deoxyribonuclease I. Because we previously found a positive relationship between pol λ inhibition and anti-inflammatory action, we examined whether these compounds could inhibit inflammatory responses. Among the five compounds tested, MK-2 caused the greatest reduction in 12-O-tetradecanoylphorbol-13-acetate (TPA-induced acute inflammation in mouse ear. In addition, in a cell culture system using mouse macrophages, MK-2 displayed the strongest suppression of the production of tumor necrosis factor (TNF-α induced by lipopolysaccharide (LPS. Moreover, MK-2 was found to inhibit the action of nuclear factor (NF-κB. In an in vivo mouse model of LPS-evoked acute inflammation, intraperitoneal injection of MK-2 in mice led to suppression of TNF-α production in serum. In conclusion, this study has identified VK2 and VK3 intermediates, such as MK-2, that are promising anti-inflammatory candidates.

  2. Determination of the phenolic content, profile, and antioxidant activity of seeds from nine tree peony (Paeonia section Moutan DC.) species native to China.

    Science.gov (United States)

    Zhang, Xiao-Xiao; Shi, Qian-Qian; Ji, Duo; Niu, Li-Xin; Zhang, Yan-Long

    2017-07-01

    As an important resource of functional food, the seeds of tree peony are rich in phenolic compounds, which are associated with antioxidant activity. However, so far there has not been systematic study on phenolic compositions and antioxidant activity of the seeds from wild tree peony species. The aim of this study was to determine the phenolic content, antioxidant compounds and antioxidant activity of seeds from nine tree peony species native to China. Among the seed samples, Paeonia rockii had the highest total flavonoid content, strongest DPPH and ABTS radical scavenging activities, and strongest cupric reducing capacity; P. decomposita subsp. rotundiloba had the highest total phenolic and flavanol contents, as well as the strongest hydroxyl radical scavenging activity. Sixteen individual phenolic compounds were quantitatively measured, with (+)-catechin being the most abundant component. The content of the phenolic compounds luteolin, paeonol, and the total flavonoid content were significantly correlated with four antioxidant activities. Hierarchical cluster analysis showed that P. rockii and P. decomposita subsp. rotundiloba could be clustered in a group having a high phenolic content and strong antioxidant activity. These results suggest P. rockii and P. decomposita subsp. rotundiloba are the most promising candidates as useful sources of natural antioxidants. Copyright © 2017. Published by Elsevier Ltd.

  3. GRL-09510, a Unique P2-Crown-Tetrahydrofuranylurethane -Containing HIV-1 Protease Inhibitor, Maintains Its Favorable Antiviral Activity against Highly-Drug-Resistant HIV-1 Variants in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Amano, Masayuki; Miguel Salcedo-Gómez, Pedro; Yedidi, Ravikiran S.; Delino, Nicole S.; Nakata, Hirotomo; Venkateswara Rao, Kalapala; Ghosh, Arun K.; Mitsuya, Hiroaki

    2017-09-25

    We report that GRL-09510, a novel HIV-1 protease inhibitor (PI) containing a newly-generated P2-crown-tetrahydrofuranylurethane (Crwn-THF), a P2'-methoxybenzene, and a sulfonamide isostere, is highly active against laboratory and primary clinical HIV-1 isolates (EC50: 0.0014–0.0028 μM) with minimal cytotoxicity (CC50: 39.0 μM). Similarly, GRL-09510 efficiently blocked the replication of HIV-1NL4-3 variants, which were capable of propagating at high-concentrations of atazanavir, lopinavir, and amprenavir (APV). GRL-09510 was also potent against multi-drug-resistant clinical HIV-1 variants and HIV-2ROD. Under the selection condition, where HIV-1NL4-3 rapidly acquired significant resistance to APV, an integrase inhibitor raltegravir, and a GRL-09510 congener (GRL-09610), no variants highly resistant against GRL-09510 emerged over long-term in vitro passage of the virus. Crystallographic analysis demonstrated that the Crwn-THF moiety of GRL-09510 forms strong hydrogen-bond-interactions with HIV-1 protease (PR) active-site amino acids and is bulkier with a larger contact surface, making greater van der Waals contacts with PR than the bis-THF moiety of darunavir. The present data demonstrate that GRL-09510 has favorable features for treating patients infected with wild-type and/or multi-drug-resistant HIV-1 variants, that the newly generated P2-Crwn-THF moiety confers highly desirable anti-HIV-1 potency. The use of the novel Crwn-THF moiety sheds lights in the design of novel PIs.

  4. Screening of various botanical extracts for antioxidant activity using DPPH free radical method.

    Science.gov (United States)

    Waqas, Muhammad Khurram; Saqib, Najam-Us; Rashid, Saeed-Ur; Shah, Pervaiz Akhtar; Akhtar, Naveed; Murtaza, Ghulam

    2013-01-01

    Aiming at the exploration of herbal use by society, crude extracts of the seeds of some commonly used medicinal plants (Vitis vinifera, Tamarindus indica and Glycin max) were screened for their free radical scavenging properties using ascorbic acid as standard antioxidant. Free radical scavenging activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical. The overall antioxidant activity of grape seeds (Vitis vinifera) was the strongest, followed in descending order by soybean (Glycin max) and tamarind (Tamarindus indica). The seeds extract of Vitis vinifera, Glycin max and Tamarindus indica showed 85.61%, 83.45% and 79.26%, DPPH scavenging activity respectively.

  5. Synthesis and Biological Evaluation of 3-Benzylidene-4-chromanone Derivatives as Free Radical Scavengers and α-Glucosidase Inhibitors.

    Science.gov (United States)

    Takao, Koichi; Yamashita, Marimo; Yashiro, Aruki; Sugita, Yoshiaki

    2016-01-01

    A series of 3-benzylidene-4-chromanone derivatives (3-20) were synthesized and the structure-activity relationships for antioxidant and α-glucosidase inhibitory activities were evaluated