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Sample records for acetylcholinesterase inhibitory activity

  1. Antioxidative/acetylcholinesterase inhibitory activity of some Asteraceae plants.

    Mekinić, Ivana Generalić; Burcul, Franko; Blazević, Ivica; Skroza, Danijela; Kerum, Daniela; Katalinić, Visnja

    2013-04-01

    The extracts obtained by 80% EtOH from some Asteraceae plants (Calendula officinalis, Inula helenium, Arctium lappa, Artemisia absinthium and Achillea millefolium) were studied. Rosmarinic acid, one of the main compounds identified in all extracts, was determined quantitatively by using HPLC. In addition, spectrophotometric methods were evaluated as an alternative for rosmarinic acid content determination. Total phenolic content was also established for all extracts. A. millefolium extract was found to have the highest content of rosmarinic acid as well as total phenols. All extracts were tested for antioxidant and acetylcholinesterase inhibitory activity. A. millefolium was shown to possess the best antioxidant activity (for all tested methods) as well as acetylcholinesterase inhibitory activity. Highly positive linear relationships were obtained between antioxidant/acetylcholinesterase inhibitory activity and the determined rosmarinic acid content indicating its significance for the observed activities. PMID:23738456

  2. Chemical Constituents of Jacaranda oxyphylla and their Acetylcholinesterase Inhibitory and Antimicrobial Activities

    Vinicius Viana Pereira

    2015-10-01

    Full Text Available This study evaluated chemical composition of Jacaranda oxyphylla, acetylcholinesterase inhibitory and antimicrobial activities of the isolated compounds. Phytochemical investigation of leaves extract yielded three classes of substances: fatty compounds, sterols and triterpenes. Butyl hexadecanoate (1, fatty alcohol (2, 2-(4-hydroxyphenylethyl triacontanoate (3, β -sitosterol (4, sitosterol-3-O- β- D -glucoside (5, 6'-palmitoyl-sitosterol-3-O- β- D -glucoside (6, oleanolic acid (7, ursolic acid (8 and corosolic acid (9 were obtained from n-hexane, CHCl 3 and EtOH extracts of J. oxyphylla. It was found a pronounced acetylcholinesterase inhibitory activity for the fatty compounds 1-3 and sterols 5 and 6, with values between 60 to 77%. Substances 7-9 presented a high antibacterial action against Bacillus cereus and Salmonella typhimurium, with values of growth inhibition in the range of 84 to 90%.

  3. Acetylcholinesterase Inhibitory Activities of Flavonoids from the Leaves of Ginkgo biloba against Brown Planthopper

    Xiao Ding

    2013-01-01

    Full Text Available Ginkgo biloba is a traditional Chinese medicinal plant which has potent insecticidal activity against brown planthopper. The MeOH extract was tested in the acetylcholinesterase (AChE inhibitory assay with IC50 values of 252.1 μg/mL. Two ginkgolides and thirteen flavonoids were isolated from the leaves of Ginkgo biloba. Their structures were established on the basis of spectroscopic data interpretation. It revealed that the 13 isolated flavonoids were found to inhibit AChE with IC50 values ranging from 57.8 to 133.1 μg/mL in the inhibitory assay. AChE was inhibited dose dependently by all tested flavonoids, and compound 6 displayed the highest inhibitory effect against AChE with IC50 values of 57.8 μg/mL.

  4. Acetylcholinesterase Inhibitory Activities of Flavonoids from the Leaves of Ginkgo biloba against Brown Planthopper

    Xiao Ding; Ming-An Ouyang; Xiang Liu; Rei-Zhen Wang

    2013-01-01

    Ginkgo biloba is a traditional Chinese medicinal plant which has potent insecticidal activity against brown planthopper. The MeOH extract was tested in the acetylcholinesterase (AChE) inhibitory assay with IC50 values of 252.1 μg/mL. Two ginkgolides and thirteen flavonoids were isolated from the leaves of Ginkgo biloba. Their structures were established on the basis of spectroscopic data interpretation. It revealed that the 13 isolated flavonoids were found to inhibit AChE with IC50 values ra...

  5. Synthesis of Some Phenylpropanoid Glycosides (PPGs) and Their Acetylcholinesterase/Xanthine Oxidase Inhibitory Activities

    Jin-Hui Wang; Xiao-Dong Li; Shuai-Tao Kang; Guo-Yu Li; Xian Li

    2011-01-01

    In this research, three categories of phenylpropanoid glycosides (PPGs) were designed and synthesized with PPGs isolated from Rhodiola rosea L. as lead compounds. Their inhibitory abilities toward acetylcholinesterase (AChE) and xanthine oxidase (XOD) were also tested. Some of the synthetic PPGs exhibited excellent enzyme inhibitory abilities.

  6. Synthesis of Some Phenylpropanoid Glycosides (PPGs and Their Acetylcholinesterase/Xanthine Oxidase Inhibitory Activities

    Jin-Hui Wang

    2011-04-01

    Full Text Available In this research, three categories of phenylpropanoid glycosides (PPGs were designed and synthesized with PPGs isolated from Rhodiola rosea L. as lead compounds. Their inhibitory abilities toward acetylcholinesterase (AChE and xanthine oxidase (XOD were also tested. Some of the synthetic PPGs exhibited excellent enzyme inhibitory abilities.

  7. Screening the methanol extracts of some Iranian plants for acetylcholinesterase inhibitory activity

    Gholamhoseinian, A; Moradi, M.N.; Sharifi-far, F.

    2009-01-01

    Acetylcholinesterase (AChE) is the main enzyme for the breakdown of acetylcholine. Nowadays, usage of the inhibitors of this enzyme is one of the most important types of treatment of mild to moderate neurodegenerative diseases such as Alzheimer’s disease. Herbal medicines can be a new source of inhibitors of this enzyme. In this study we examined around 100 different plants to evaluate their inhibitory properties for AChE enzyme. Plants were scientifically identified and their extracts were p...

  8. Acetylcholinesterase inhibitory, antioxidant, and antimicrobial activities of Salvia tomentosa Mill. essential oil

    ANDREY MARCHEV

    2015-08-01

    Full Text Available Chemical composition and bioactivity of essential oil from Salvia tomentosa Mill. natively grown in Bulgaria were investigated. GC-MS analysis identified 60 compounds which represented 98% of the oil constituents. The prevalent constituents were monoterpenes with eight dominant compounds being identified: borneol (10.3%, β-pinene (9%, camphor (7.9%, α-pinene (6%, camphene (4%, 1.8-cineole (3.8%, α-limonene (3.5% and β-caryophyllene (3%. The essential oil showed considerable acetylcholinesterase inhibitory activity (IC50=0.28±0.06 µg/mL, comparable with that of galanthamine. Study of antioxidant activity strongly suggested that the hydrogen atom transfer reaction was preferable over the electron transfer (ORAC=175.0±0.40 µM Trolox equivalents/g oil and FRAP=1.45±0.21 mM Trolox equivalents/g oil. The essential oil showed moderate antifungal and antibacterial activities against Candida albicans and Gram-positive bacteria, whereas it was almost inactive against the investigated Gram-negative strains. The results suggested that the essential oil of Bulgarian S. tomentosa could be considered as a prospective active ingredient for prevention of oxidative stress-related and neurodegenerative disorders in aromatherapy. Because of the high antioxidant capacity, the oil could be considered as natural supplement or antioxidant in cosmetics and food products.

  9. An Expedient Synthesis, Acetylcholinesterase Inhibitory Activity, and Molecular Modeling Study of Highly Functionalized Hexahydro-1,6-naphthyridines

    Almansour, Abdulrahman I.; Raju Suresh Kumar; Natarajan Arumugam; Alireza Basiri; Yalda Kia; Mohamed Ashraf Ali

    2015-01-01

    A series of hexahydro-1,6-naphthyridines were synthesized in good yields by the reaction of 3,5-bis[(E)-arylmethylidene]tetrahydro-4(1H)-pyridinones with cyanoacetamide in the presence of sodium ethoxide under simple mixing at ambient temperature for 6–10 minutes and were assayed for their acetylcholinesterase (AChE) inhibitory activity using colorimetric Ellman’s method. Compound 4e with methoxy substituent at ortho-position of the phenyl rings displayed the maximum inhibitory activity with ...

  10. Acetylcholinesterase and butyrylcholinesterase inhibitory activity of some selected Nigerian medicinal plants

    Taiwo O. Elufioye

    2010-09-01

    Full Text Available Plants have been found to be useful as memory enhansers as well as antiaging. Twenty two of such plants from sixteen families were investigated for their acetylcholinesterase (AChE and butyrylcholinesterase (BuChE inhibitory activities using the in vitro Ellman's spectrophotometric and in situ bioautographic methods with physostigmine as standard. At least three morphological parts were examined for each of the plants investigated and the test concentration was 42.5 µg/ mL. Some plants were active on both enzymes though with some morphological parts being more active than others. The root bark of Spondias mombin showed the highest activity to the two enzymes; 64.77% and 83.94% on AChE and BuChE respectively. Other plant parts of the selected plants exhibited some remarkable selectivity in their actions. Those selectively active against AChE were Alchornia laxiflora stem bark (41.12% and root bark, Callophyllum inophyllurn root bark (56.52%. The leaves of C. jagus (74.25%, Morinda lucida leaves (40.15%, Peltophorum pterocarpum leaves and stem bark (49.5% and 68.85%, respectively, physiostigmine gave 90.31% inhibition. Generally higher activities were found against BuChE. Bombax bromoposenze leaves, root bark and stem bark were particularly active. The inhibition was over 80%. Other selective plant parts are the leaves Antiaris africana, Cissampelos owarensis aerial parts (78.96%, Combretum molle leaves and stem bark (90.42% and 88.13%, respectively, Dioscorea dumentorum root bark and tuber (over 87%, G. kola leaves, Markhamia tomentosa root bark, Pycnanthus angolensis stem bark and Tetrapleura tetraptera leaves. Most of these plants are taken as food or are food ingredients in Nigeria and may account for the low incidence of Alzheimer's disease in the country and may play certain roles in the mediation of the disease.

  11. Evaluation of acetylcholinesterase inhibitory activity of Brazilian red macroalgae organic extracts

    Levi P. Machado

    2015-12-01

    Full Text Available Abstract Alzheimer's disease affects nearly 36.5 million people worldwide, and acetylcholinesterase inhibition is currently considered the main therapeutic strategy against it. Seaweed biodiversity in Brazil represents one of the most important sources of biologically active compounds for applications in phytotherapy. Accordingly, this study aimed to carry out a quantitative and qualitative assessment of Hypnea musciformis (Wulfen J.V. Lamouroux, Ochtodes secundiramea (Montagne M.A. Howe, and Pterocladiella capillacea (S.G. Gmelin Santelices & Hommersand (Rhodophyta in order to determine the AChE effects from their extracts. As a matter of fact, the O. secundiramea extract showed 48% acetylcholinesterase inhibition at 400 μg/ml. The chemical composition of the bioactive fraction was determined by gas chromatography–mass spectrometry (GC–MS; this fraction is solely composed of halogenated monoterpenes, therefore allowing assignment of acetylcholinesterase inhibition activity to them.

  12. Acetylcholinesterase inhibitory activity of lycopodane-type alkaloids from the Icelandic Lycopodium annotinum ssp. alpestre

    Halldórsdóttir, Elsa Steinunn; Jaroszewski, Jerzy W; Olafsdottir, Elin Soffia

    The aim of this study was to investigate structures and acetylcholinesterase inhibitory activities of lycopodane-type alkaloids isolated from an Icelandic collection of Lycopodium annotinum ssp. alpestre. Ten alkaloids were isolated, including annotinine, annotine, lycodoline, lycoposerramine M...... determined. Conformation of acrifoline was characterized using NOESY spectroscopy and molecular modelling. The isolated alkaloids were evaluated for their in vitro inhibitory activity against acetylcholinesterase and butyrylcholinesterase. Ligand docking studies based on mutated 3D structure of Torpedo...... californica acetylcholinesterase provided rationale for low inhibitory activity of the isolated alkaloids as compared to huperzine A or B, which are potent acetylcholinesterase inhibitors belonging to the lycodine class. Based on the modelling studies the lycopodane-type alkaloids seem to fit well into the...

  13. Graveoline Analogs Exhibiting Selective Acetylcholinesterase Inhibitory Activity as Potential Lead Compounds for the Treatment of Alzheimer’s Disease

    Zeng Li

    2016-01-01

    Full Text Available This study designed and synthesized a series of new graveoline analogs on the basis of the structural characteristics of acetylcholinesterase (AChE dual-site inhibitors. The activity of these analogs was also evaluated. Results showed that the synthesized graveoline analogs displayed stronger inhibitory activity against AChE and higher selectivity than butyrylcholine esterase (BuChE (Selectivity Index from 45 to 486. When the two sites in the graveoline parent ring substituting phenyl and amino terminal had six chemical bonds (n = 3 and the terminal amino was piperidine, compound 5c showed the best activity. Furthermore, the mechanism of action and binding mode were explored by enzyme kinetic simulation, molecular docking, and thioflavin T-based fluorometric assay. Cytotoxicity assay showed that the low concentration of the analogs did not affect the viability of the neurocyte SH-SY5Y.

  14. Characterization of Lignanamides from Hemp (Cannabis sativa L.) Seed and Their Antioxidant and Acetylcholinesterase Inhibitory Activities.

    Yan, Xiaoli; Tang, Jiajing; dos Santos Passos, Carolina; Nurisso, Alessandra; Simões-Pires, Claudia Avello; Ji, Mei; Lou, Hongxiang; Fan, Peihong

    2015-12-16

    Hemp seed is known for its content of fatty acids, proteins, and fiber, which contribute to its nutritional value. Here we studied the secondary metabolites of hemp seed aiming at identifying bioactive compounds that could contribute to its health benefits. This investigation led to the isolation of 4 new lignanamides, cannabisin M (2), cannabisin N (5), cannabisin O (8), and 3,3'-demethyl-heliotropamide (10), together with 10 known lignanamides, among which 4 was identified for the first time from hemp seed. Structures were established on the basis of NMR, HR-MS, UV, and IR as well as by comparison with the literature data. Lignanamides 2, 7, and 9-14 showed good antioxidant activity, among which 7, 10, and 13 also inhibited acetylcholinesterase in vitro. The newly identified compounds in this study add to the diversity of hemp seed composition, and the bioassays implied that hemp seed, with lignanamides as nutrients, may be a good source of bioactive and protective compounds. PMID:26585089

  15. In vitro inhibitory effect of aflatoxin B1 on acetylcholinesterase activity in mouse brain.

    Cometa, Maria Francesca; Lorenzini, Paola; Fortuna, Stefano; Volpe, Maria Teresa; Meneguz, Annarita; Palmery, Maura

    2005-01-01

    Growing concern on the problem of mycotoxins in the alimentary chain underlines the need to investigate the mechanisms explaining the cholinergic effects of aflatoxin B(1) (AFB(1)). We examined the effect of AFB(1), a mycotoxin produced by Aspergillus flavus, on mouse brain acetylcholinesterase (AChE) and specifically on its molecular isoforms (G(1) and G(4)) after in vitro exposure. AFB(1) (from 10(-9) to 10(-4)M), inhibited mouse brain AChE activity (IC(50) = 31.6 x 10(-6)M) and its G(1) and G(4) molecular isoforms in a dose-dependent manner. Michaelis-Menten parameters indicate that the K(m) value increased from 55.2 to 232.2% whereas V(max) decreased by 46.2-75.1%. The direct, the Lineweaver-Burk and the secondary plots indicated a non-competitive-mixed type antagonism, induced when the inhibitor binds to the free enzyme and to the enzyme-substrate complex. AFB(1)-inhibited AChE was partially reactivated by pyridine 2-aldoxime (2-PAM) (10(-4)M) but the AChE-inhibiting time courses of AFB(1) (10(-4)M) and diisopropylfluorophosphate (DFP) (2 x 10(-7)M) differed. Overall these data suggest that AFB(1) non-competitively inhibits mouse brain AChE by blocking access of the substrate to the active site or by inducing a defective conformational change in the enzyme through non-covalent binding interacting with the AChE peripheral binding site, or through both mechanisms. PMID:15590113

  16. Screening for acetylcholinesterase inhibitory activity in cyanobacteria of the genus Nostoc

    Zelík, Petr; Lukešová, Alena; Voloshko, L. N.; Štys, D.; Kopecký, Jiří

    2009-01-01

    Roč. 24, č. 2 (2009), s. 531-536. ISSN 1475-6366 R&D Projects: GA MŠk ME 874 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z60660521 Keywords : acetylcholinesterase * bioactivity * inhibitors Subject RIV: EE - Microbiology, Virology Impact factor: 1.496, year: 2009

  17. Sesquiterpenes and a monoterpenoid with acetylcholinesterase (AchE) inhibitory activity from Valeriana officinalis var. latiofolia in vitro and in vivo.

    Chen, Heng-Wen; He, Xuan-Hui; Yuan, Rong; Wei, Ben-Jun; Chen, Zhong; Dong, Jun-Xing; Wang, Jie

    2016-04-01

    Acetylcholinesterase Inhibitor (AchEI) is the most extensive in all anti-dementia drugs. The extracts and isolated compounds from the Valeriana genus have shown anti-dementia bioactivity. Four new sesquiterpenoids (1-4) and a new monoterpenoid (5) were isolated from the root of Valeriana officinalis var. latiofolia. The acetylcholinesterase (AchE) inhibitory activity of isolates was evaluated by modified Ellman method in vitro. Learning and memory ability of compound 4 on mice was evaluated by the Morris water maze. The contents of acetylcholine (Ach), acetylcholine transferase (ChAT) and AchE in mice brains were determined by colorimetry. The results showed IC50 of compound 4 was 0.161μM in vitro. Compared with the normal group, the learning and memory ability of mice and the contents of Ach and ChAT decreased in model group mice (Penzyme in the cholinergic system. PMID:26976216

  18. Synthesis of Benzofuran Derivatives via Rearrangement and Their Inhibitory Activity on Acetylcholinesterase

    Ling-Yi Kong

    2010-11-01

    Full Text Available During a synthesis of coumarins to obtain new candidates for treating Alzheimer’s Disease (AD, an unusual rearrangement of a benzopyran group to a benzofuran group occurred, offering a novel synthesis pathway of these benzofuran derivatives. The possible mechanism of the novel rearrangement was also discussed. All of the benzofuran derivatives have weak anti-AChE activities compared with the reference compound, donepezil.

  19. Acetylcholinesterase inhibitory effects of some plants from Rosaceae

    S. Esmaeili

    2015-10-01

    Full Text Available Background and objectives: Alzheimer's disease (AD is an age dependent disorder. AD is associated with decrease of brain acetylcholine level. Nowadays, one of the methods for progression inhibition of AD is using acetylcholinesterase inhibitors. Rosaceae is a large plant family. Different biological effects of some species of this family have been reported. The aim of the present study was to assess the acetylcholinesterase inhibitory (AChEI activity of the selected plants belonging to Rosaceae family. Methods: AChEI activity of six species from Rosaceae including Cotoneaster nummularia, Cerasus microcarpa, Amygdalus scoparia, Agrimonia eupatoria, Rosa canina and Rosa damascena were evaluated based on Ellman’s method in concentration of 300 µg/mL using total extracts and methanol fractions which were obtained by maceration. Results: The results showed that the total extract and methanol fraction of the aerial parts of A. eupatoria demonstrated significant AChEI activity with 46.5% and 56.2% inhibition of the enzyme, respectively. Conclusion: According to the results of the AChEI activity of the methanol fraction of A. eupatoria, it seems that the polar components of the species such as flavonoids may be responsible for its effectiveness.

  20. Antioxidant and acetylcholinesterase inhibitory potential of Arnica montana cultivated in Bulgaria

    Zheleva-Dimitrova, Dimitrina; BALABANOVA, Vessela

    2012-01-01

    The antioxidant and acetylcholinesterase inhibitory potential of methanol extract from Arnica montana cultivated in Bulgaria was evaluated. For the determination of antioxidant activity 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) di-ammonium salt (ABTS) free radicals, and ferric reducing antioxidant power (FRAP) assay were used. Modified Ellman's colorimetric method was used for quantitative assessment of acetylcholinesterase inhibiti...

  1. Larvicidal and acetylcholinesterase inhibitory activities of apiaceae plant essential oils and their constituents against aedes albopictus and formulation development.

    Seo, Seon-Mi; Jung, Chan-Sik; Kang, Jaesoon; Lee, Hyo-Rim; Kim, Sung-Woong; Hyun, Jinho; Park, Il-Kwon

    2015-11-18

    This study evaluated the larvicidal activity of 12 Apiaceae plant essential oils and their components against the Asian tiger mosquito, Aedes albopictus, and the inhibition of acetylcholine esterase with their components. Of the 12 plant essential oils tested, ajowan (Trachyspermum ammi), caraway seed (Carum carvi), carrot seed (Daucus carota), celery (Apium graveolens), cumin (Cuminum cyminum), dill (Anethum graveolens), and parsley (Petroselinum sativum) resulted in >90% larval mortality when used at 0.1 mg/mL. Of the compounds identified, α-phellandrene, α-terpinene, p-cymene, (-)-limonene, (+)-limonene, γ-terpinene, cuminaldehyde, neral, (S)-+-carvone, trans-anethole, thymol, carvacrol, myristicin, apiol, and carotol resulted in >80% larval mortality when used at 0.1 mg/mL. Two days after treatment, 24.69, 3.64, and 12.43% of the original amounts of the celery, cumin, and parsley oils, respectively, remained in the water. Less than 50% of the original amounts of α-phellandrene, 1,8-cineole, terpinen-4-ol, cuminaldehyde, and trans-antheole were detected in the water at 2 days after treatment. Carvacrol, α-pinene, and β-pinene inhibited the activity of Ae. albopictus acetylcholinesterase with IC50 values of 0.057, 0.062, and 0.190 mg/mL, respectively. A spherical microemulsion of parsley essential oil-loaded poly(vinyl alcohol) (PVA) was prepared, and the larvicidal activity of this formulation was shown to be similar to that of parsley oil. PMID:26500081

  2. Acetylcholinesterase Inhibitory, Antioxidant and Phytochemical Properties of Selected Medicinal Plants of the Lamiaceae Family

    Sanda Vladimir-Knežević; Biljana Blažeković; Marija Kindl; Jelena Vladić; Lower-Nedza, Agnieszka D.; Brantner, Adelheid H.

    2014-01-01

    The present study aimed to evaluate acetylcholinesterase (AChE) inhibitory and antioxidant activities of Lamiaceae medicinal plants growing wild in Croatia. Using Ellman’s colorimetric assay all tested ethanolic extracts and their hydroxycinnamic acid constituents demonstrated in vitro AChE inhibitory properties in a dose dependent manner. The extracts of Mentha x piperita, M. longifolia, Salvia officinalis, Satureja montana, Teucrium arduini, T. chamaedrys, T. montanum, T. polium and Thymus ...

  3. In-vitro screening of acetylcholinesterase inhibitory activity of extracts from Palestinian indigenous flora in relation to the treatment of Alzheimer’s disease

    Mohammed Saleem Ali-Shtayeh

    2014-09-01

    Full Text Available Background: Cholinesterase inhibitory therapy serves as a strategy for the treatment of Alzheimer’s disease (AD. Several acetylcholinesterase inhibitors (AChEIs are used for the symptomatic treatment of AD. These compounds have been reported to have adverse effects, including gastrointestinal disturbances. This study was therefore partly aimed at investigating in vitro possible AChEIs in herbal medicines traditionally used in Palestine to treat cognitive disorders, and to point out the role of these plants as potential sources for development of newly potent and safe natural therapeutic agents of AD. Assay of AChE activity plays an important role in vitro characterization of drugs including potential treatments for AD. The most widely used method, is based on Ellman’s method. The reactant used in this method shows chemical reactivity with oxime antidots and thiol leading to false positive reactions. A new alternative assay could be of high interest. Methods: The effect on AChE activity of 92 extracts of 47 medicinal plants were evaluated using a new micro-well plate AChE activity (NA-FB and Ellman’s assays. In addition, antioxidant activity using DPPH was determined. Results: The main advantages of the new method (NA-FB is that the colorimetric change is better observable visually allowing spectrophotometric as well as colorimetric assay, and does not show any chemical reactivity with thiol. 67.4% and 37% of extracts inhibited AChE by >50% using the NA-FB and Ellman’s assays, respectively. Using NA-FB assay, 84 extracts interacted reversibly with the enzyme, of which Mentha spicata (94.8%, Foeniculum vulgare (89.81, and Oxalis pes-caprae (89.21 were most potent, and 8 showed irreversible inhibition of which leaves of Lupinus pilosus (92.02% were most active. Antioxidant activity was demonstrated by 73 extracts Majorana syriaca (IC50 0.21mg/ml, and Rosmarinus officinalis (0.38 were the most active. Conclusions: NA-FB assay has shown to be

  4. Laboratory and Simulated Field Bioassays to Evaluate Larvicidal Activity of Pinus densiflora Hydrodistillate, Its Constituents and Structurally Related Compounds against Aedes albopictus, Aedes aegypti and Culex pipiens pallens in Relation to Their Inhibitory Effects on Acetylcholinesterase Activity.

    Lee, Dong Chan; Ahn, Young-Joon

    2013-01-01

    The toxicity of Pinus densiflora (red pine) hydrodistillate, its 19 constituents and 28 structurally related compounds against early third-instar larvae of Aedes albopictus (Ae. albopictus), Aedes aegypti (Ae. aegypti) and Culex pipiens palles (Cx. p. pallens) was examined using direct-contact bioassays. The efficacy of active compounds was further evaluated in semi-field bioassays using field-collected larval Cx. p. pallens. Results were compared with those of two synthetic larvicides, temephos and fenthion. In laboratory bioassays, Pinus densiflora hydrodistillate was found to have 24 h LC50 values of 20.33, 21.01 and 22.36 mg/L against larval Ae. albopictus, Ae. aegypti and Cx. p. pallens respectively. Among the identified compounds, thymol, δ-3-carene and (+)-limonene exhibited the highest toxicity against all three mosquito species. These active compounds were found to be nearly equally effective in field trials as well. In vitro bioassays were conducted to examine the acetylcholinesterase (AChE) inhibitory activity of 10 selected compounds. Results showed that there is a noticeable correlation between larvicidal activity and AChE inhibitory activity. In light of global efforts to find alternatives for currently used insecticides against disease vector mosquitoes, Pinus densiflora hydrodistillate and its constituents merit further research as potential mosquito larvicides. PMID:26464387

  5. Laboratory and Simulated Field Bioassays to Evaluate Larvicidal Activity of Pinus densiflora Hydrodistillate, Its Constituents and Structurally Related Compounds against Aedes albopictus, Aedes aegypti and Culex pipiens pallens in Relation to Their Inhibitory Effects on Acetylcholinesterase Activity

    Young-Joon Ahn

    2013-05-01

    Full Text Available The toxicity of Pinus densiflora (red pine hydrodistillate, its 19 constituents and 28 structurally related compounds against early third-instar larvae of Aedes albopictus (Ae. albopictus, Aedes aegypti (Ae. aegypti and Culex pipiens palles (Cx. p. pallens was examined using direct-contact bioassays. The efficacy of active compounds was further evaluated in semi-field bioassays using field-collected larval Cx. p. pallens. Results were compared with those of two synthetic larvicides, temephos and fenthion. In laboratory bioassays, Pinus densiflora hydrodistillate was found to have 24 h LC50 values of 20.33, 21.01 and 22.36 mg/L against larval Ae. albopictus, Ae. aegypti and Cx. p. pallens respectively. Among the identified compounds, thymol, δ-3-carene and (+-limonene exhibited the highest toxicity against all three mosquito species. These active compounds were found to be nearly equally effective in field trials as well. In vitro bioassays were conducted to examine the acetylcholinesterase (AChE inhibitory activity of 10 selected compounds. Results showed that there is a noticeable correlation between larvicidal activity and AChE inhibitory activity. In light of global efforts to find alternatives for currently used insecticides against disease vector mosquitoes, Pinus densiflora hydrodistillate and its constituents merit further research as potential mosquito larvicides.

  6. Fumigant toxicity of Oriental sweetgum (Liquidambar orientalis) and valerian (Valeriana wallichii) essential oils and their components, including their acetylcholinesterase inhibitory activity, against Japanese termites (Reticulitermes speratus).

    Park, Il-Kwon

    2014-01-01

    This study investigated the fumigant toxicity of oriental sweetgum (Liquidambar orientalis) and valerian (Valeriana wallichii) essential oils and their components against the Japanese termite (Reticulitermes speratus). The fumigant toxicity of oriental sweetgum and valerian oil differed significantly according to exposure time. Oriental sweetgum showed toxicity at short exposure times (2 days), and the toxicity of valerian oil was high 7 days after treatment. The main constituents of oriental sweetgum and valerian oils were tested individually for their fumigant toxicity against Japanese termites. Among the test compounds, benzyl alcohol, acetophenone, 1-phenyl-1-ethanol, hydrocinnamyl alcohol, trans-cinnamyl aldehyde, trans-cinnamyl alcohol, cis-asarone, styrene, and cis-ocimene showed toxicity against Japanese termites 7 days after treatment. Hydrocinnamyl alcohol and trans-cinnamyl alcohol were found to be the major contributors to the fumigant antitermitic toxicity of oriental sweetgum oil. The acetylcholinesterase (AChE) inhibition activity of two oils and their constituents was tested to determine their mode of action. Only cis-ocimene showed strong AChE inhibition activity with an IC50 value of 0.131 mg/mL. Further studies are warranted to determine the potential of these essential oils and their constituents as fumigants for termite control. PMID:25153870

  7. Fumigant Toxicity of Oriental Sweetgum (Liquidambar orientalis and Valerian (Valeriana wallichii Essential Oils and Their Components, Including Their Acetylcholinesterase Inhibitory Activity, against Japanese Termites (Reticulitermes speratus

    Il-Kwon Park

    2014-08-01

    Full Text Available This study investigated the fumigant toxicity of oriental sweetgum (Liquidambar orientalis and valerian (Valeriana wallichii essential oils and their components against the Japanese termite (Reticulitermes speratus. The fumigant toxicity of oriental sweetgum and valerian oil differed significantly according to exposure time. Oriental sweetgum showed toxicity at short exposure times (2 days, and the toxicity of valerian oil was high 7 days after treatment. The main constituents of oriental sweetgum and valerian oils were tested individually for their fumigant toxicity against Japanese termites. Among the test compounds, benzyl alcohol, acetophenone, 1-phenyl-1-ethanol, hydrocinnamyl alcohol, trans-cinnamyl aldehyde, trans-cinnamyl alcohol, cis-asarone, styrene, and cis-ocimene showed toxicity against Japanese termites 7 days after treatment. Hydrocinnamyl alcohol and trans-cinnamyl alcohol were found to be the major contributors to the fumigant antitermitic toxicity of oriental sweetgum oil. The acetylcholinesterase (AChE inhibition activity of two oils and their constituents was tested to determine their mode of action. Only cis-ocimene showed strong AChE inhibition activity with an IC50 value of 0.131 mg/mL. Further studies are warranted to determine the potential of these essential oils and their constituents as fumigants for termite control.

  8. Antioxidant and acetylcholinesterase-inhibitory properties of long-term stored medicinal plants

    Amoo Stephen O

    2012-07-01

    Full Text Available Abstract Background Medicinal plants are possible sources for future novel antioxidant compounds in food and pharmaceutical formulations. Recent attention on medicinal plants emanates from their long historical utilisation in folk medicine as well as their prophylactic properties. However, there is a dearth of scientific data on the efficacy and stability of the bioactive chemical constituents in medicinal plants after prolonged storage. This is a frequent problem in African Traditional Medicine. Methods The phytochemical, antioxidant and acetylcholinesterase-inhibitory properties of 21 medicinal plants were evaluated after long-term storage of 12 or 16 years using standard in vitro methods in comparison to freshly harvested materials. Results The total phenolic content of Artemisia afra, Clausena anisata, Cussonia spicata, Leonotis intermedia and Spirostachys africana were significantly higher in stored compared to fresh materials. The flavonoid content were also significantly higher in stored A. afra, C. anisata, C. spicata, L. intermedia, Olea europea and Tetradenia riparia materials. With the exception of Ekebergia capensis and L. intermedia, there were no significant differences between the antioxidant activities of stored and fresh plant materials as measured in the β-carotene-linoleic acid model system. Similarly, the EC50 values based on the 2,2-diphenyl-1-picrylhydrazyl (DPPH free radical scavenging assay were generally lower for stored than fresh material. Percentage inhibition of acetylcholinesterase was generally similar for both stored and fresh plant material. Stored plant material of Tetradenia riparia and Trichilia dregeana exhibited significantly higher AChE inhibition than the fresh material. Conclusions The current study presents evidence that medicinal plants can retain their biological activity after prolonged storage under dark conditions at room temperature. The high antioxidant activities of stable bioactive compounds in

  9. Acetylcholinesterase inhibitory properties of some benzoic acid derivatives

    Yildiz, Melike; Kiliç, Deryanur; Ünver, Yaǧmur; Şentürk, Murat; Askin, Hakan; Küfrevioǧlu, Ömer Irfan

    2016-04-01

    Acetylcholinesterase (AChE) hydrolyses the neurotransmitter acetylcholine to acetic acid and choline. AChE inhibitors are used in treatment of several neurodegeneartive disorder and Alzheimer's disease. In the present study, inhibition of AChE with some benzoic acid derivatives were investigated. 3-Chloro-benzoic acid (1), 2-hydroxy-5-sulfobenzoic acid (2), 2-(sulfooxy) benzoic acid (3), 2-hydroxybenzoic acid (4), 2,3-dimethoxybenzoic (5), and 3,4,5-trimethoxybenzoic (6) were calculated IC50 values AChE enzyme. Kinetic investigations showed that similarly to AChE inhibitors. Benzoic acid derivatives (1-6) investigated are encouraging agents which may be used as lead molecules in order to derivative novel AChE inhibitors that might be useful in medical applications.

  10. A Mechanism-based 3D-QSAR Approach for Classification and Prediction of Acetylcholinesterase Inhibitory Potency of Organophosphate and Carbamate Analogs

    Organophosphate (OP) and carbamate esters can inhibit acetylcholinesterase (AChE) by binding covalently to a serine residue in the enzyme active site, and their inhibitory potency depends largely on affinity for the enzyme and the reactivity of the ester. Despite this understandi...

  11. Antioxidant Activity and Acetylcholinesterase Inhibition of Grape Skin Anthocyanin (GSA

    Mehnaz Pervin

    2014-07-01

    Full Text Available We aimed to investigate the antioxidant and acetylcholinesterase inhibitory activities of the anthocyanin rich extract of grape skin. Grape skin anthocyanin (GSA neutralized free radicals in different test systems, such as 2,-2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS and 2,2-diphenyl-1-picrylhydrazyl (DPPH assays, to form complexes with Fe2+ preventing 2,2'-azobis(2-amidinopropane dihydrochloride (AAPH-induced erythrocyte hemolysis and oxidative DNA damage. Moreover, GSA decreased reactive oxygen species (ROS generation in isolated mitochondria thus inhibiting 2',-7'-dichlorofluorescin (DCFH oxidation. In an in vivo study, female BALB/c mice were administered GSA, at 12.5, 25, and 50 mg per kg per day orally for 30 consecutive days. Herein, we demonstrate that GSA administration significantly elevated the level of antioxidant enzymes in mice sera, livers, and brains. Furthermore, GSA inhibited acetylcholinesterase (AChE in the in vitro assay with an IC50 value of 363.61 µg/mL. Therefore, GSA could be an excellent source of antioxidants and its inhibition of cholinesterase is of interest with regard to neurodegenerative disorders such as Alzheimer’s disease.

  12. Acetylcholinesterase Inhibition and in Vitro and in Vivo Antioxidant Activities of Ganoderma lucidum Grown on Germinated Brown Rice

    Beong Ou Lim

    2013-06-01

    Full Text Available In this study, the acetylcholinesterase inhibition and in vitro and in vivo antioxidant activities of Ganoderma lucidum grown on germinated brown rice (GLBR were evaluated. In antioxidant assays in vitro, GLBR was found to have strong metal chelating activity, DPPH, ABTS, hydroxyl and superoxide radical scavenging activity. Cell-based antioxidant methods were used, including lipid peroxidation on brain homogenate and AAPH-induced erythrocyte haemolysis. In antioxidant assays in vivo, mice were administered with GLBR and this significantly enhanced the activities of antioxidant enzymes in the mice sera, livers and brains. The amount of total phenolic and flavonoid compounds were 43.14 mg GAE/g and 13.36 mg CE/g dry mass, respectively. GLBR also exhibited acetylcholinesterase inhibitory activity. In addition, HPLC analyses of GLBR extract revealed the presence of different phenolic compounds. These findings demonstrate the remarkable potential of GLBR extract as valuable source of antioxidants which exhibit interesting acetylcholinesterase inhibitory activity.

  13. Inhibitory Effects of Sodium Arsenite and Acacia Honey on Acetylcholinesterase in Rats

    Aliyu Muhammad; Oyeronke A Odunola; Michael A. Gbadegesin; Sallau, Abdullahi B.; Ndidi, Uche S.; Ibrahim, Mohammed A.

    2015-01-01

    This study was conducted to investigate the effect of sodium arsenite and Acacia honey on acetylcholinesterase (AChE) activity and electrolytes in the brain and serum of Wistar rats. Male Wistar albino rats in four groups of five rats each were treated with distilled water, sodium arsenite (5 mg/kg body weight), Acacia honey (20% v/v), and sodium arsenite and Acacia honey, daily for one week. The sodium arsenite and Acacia honey significantly P

  14. Synthesis and anti-acetylcholinesterase activity of benzotriazinone-triazole systems

    SETAREH MOGHIMI; FERESHTEH GOLI-GARMROODI; HEDIEH PILALI; MOHAMMAD MAHDAVI; LOGHMAN FIROOZPOUR; HAMID NADRI; ALIREZA MORADI; ALI ASADIPOUR; ABBAS SHAFIEE; ALIREZA FOROUMADI

    2016-09-01

    An approach for the construction of benzotriazinone-triazole system is described. The synthesis is based on diazonium chemistry and subsequent intramolecular heteroatom-heteroatom bond formation. The introduction of triazole moiety occurred via click reaction catalyzed by nano-sized copper, supported on modified silica mesopore KIT-5 leading to the desired products in excellent yield. Also, in vitro acetylcholinesterase(AChE) inhibitory activities of the target compounds were screened by Ellman’s method.

  15. Acetylcholinesterase Inhibition and Antioxidant Activity of Syzygium cumini, S. aromaticum and S. polyanthum from Indonesia

    Wulan Tri Wahyuni

    2013-01-01

    Full Text Available Acetylcholinesterase inhibition and antioxidant activity are considered to be highly correlated with Alzheimer’s disease treatment. Plants from Syzygium genus reported as potential antioxidant, however the potency of plants as acetylcholinesterase inhibitor has not been properly investigated. The present study was design to investigate the antioxidant and acetylcholinesterase inhibitory activity of three Syzygium plants, Syzygium cumini, S. aromaticum and S. polyanthum. Leaves of S. cumini, S. aromaticum, S. polyanthum and bud of S. aromaticum extracted with gradient polarity solvent consist of n-hexane, ethyl acetate and methanol. Acetylcholinesterase inhibitory activity was measured with modified Ellman method at 412 nm and physostigmine was used as positive control, meanwhile antioxidant activity measured based on 1,1-diphenyl-2-picrylhydrazil free radical scavenging test. The methanol extract of S. aromaticum leaves, S. aromaticum bud, S. polyanthum leaves and the ethyl acetate extract of S. polyanthum leaves were potential as acetylcholinesterase inhibitors. The IC50 values of the extracts respectively were 42.10±1.41; 45.25±0.07; 47.30±3.54 and 45.10±8.06 μg mL-1 when IC50 value of physostigmine was 0.01±0.002 μg mL-1. Meanwhile, antioxidant activity of potential extracts successively were 11.43±0.88, 9.26±0.25, 21.24±1.14 and 13.70±0.24 μg mL-1.

  16. In Vitro Antioxidant Properties, HIV-1 Reverse Transcriptase and Acetylcholinesterase Inhibitory Effects of Traditional Herbal Preparations Sold in South Africa

    Johannes Van Staden

    2010-10-01

    Full Text Available The antioxidant potentials for fourteen multipurpose traditional herbal preparations sold in South Africa were determined using the DPPH radical scavenging, ferric reducing power and β-carotene-linoleic acid model system, the anti-HIV-1 reverse transcriptase (RT enzyme inhibitory effects using an ELISA kit and acetylcholinesterase (AChE enzyme inhibition using the microtitre plate assay. Nine of the herbal mixtures (Umzimba omubi, Umuthi wekukhwehlela ne zilonda, Mvusa ukunzi, Umpatisa inkosi, Imbiza ephuzwato, Vusa umzimba, Supreme one hundred, Sejeso herbal mixture Ingwe® and Ingwe® special muti exhibited higher antioxidant potentials, while only four (Imbiza ephuzwato, Ingwe® muthi mixture, Sejeso herbal mixture Ingwe® and African potato extractTM showed potent activity against the RT enzyme. Nine mixtures (Imbiza ephuzwato, Umpatisa inkosi, African potato extractTM, Sejeso herbal mixture Ingwe®, Vusa umzimba; Ingwe® muthi mixture, Ibhubezi™, Lion izifozonke Ingwe® and Ingwe® special muti showed AChE enzyme inhibitory activity greater than 50%. The observed activity exhibited by some of the herbal mixtures gives some credence to the manufacturers’ claims and goes part of the way towards validating their use against certain conditions such as oxidative stress, HIV/AIDS proliferation and some mental conditions. It is however, desirable to carry out further studies to determine the effects of mixing plant species/parts in one mixture on the antioxidant potency as well as isolating active constituents from the herbal mixtures.

  17. Acetylcholinesterase and carbonic anhydrase inhibitory properties of novel urea and sulfamide derivatives incorporating dopaminergic 2-aminotetralin scaffolds.

    Özgeriş, Bünyamin; Göksu, Süleyman; Polat Köse, Leyla; Gülçin, İlhami; Salmas, Ramin Ekhteiari; Durdagi, Serdar; Tümer, Ferhan; Supuran, Claudiu T

    2016-05-15

    In the present study a series of urea and sulfamide compounds incorporating the tetralin scaffolds were synthesized and evaluated for their acetylcholinesterase (AChE), human carbonic anhydrase (CA, EC 4.2.1.1) isoenzyme I, and II (hCA I and hCA II) inhibitory properties. The urea and their sulfamide analogs were synthesized from the reactions of 2-aminotetralins with N,N-dimethylcarbamoyl chloride and N,N-dimethylsulfamoyl chloride, followed by conversion to the corresponding phenols via O-demethylation with BBr3. The novel urea and sulfamide derivatives were tested for inhibition of hCA I, II and AChE enzymes. These derivatives exhibited excellent inhibitory effects, in the low nanomolar range, with Ki values of 2.61-3.69nM against hCA I, 1.64-2.80nM against hCA II, and in the range of 0.45-1.74nM against AChE. In silico techniques such as, atomistic molecular dynamics (MD) and molecular docking simulations, were used to understand the scenario of the inhibition mechanism upon approaching of the ligands into the active site of the target enzymes. In light of the experimental and computational results, crucial amino acids playing a role in the stabilization of the enzyme-inhibitor adducts were identified. PMID:27068142

  18. In Vitro Antioxidant Properties, HIV-1 Reverse Transcriptase and Acetylcholinesterase Inhibitory Effects of Traditional Herbal Preparations Sold in South Africa

    Johannes Van Staden; Jeffrey F. Finnie; Ndhlala, Ashwell R.

    2010-01-01

    The antioxidant potentials for fourteen multipurpose traditional herbal preparations sold in South Africa were determined using the DPPH radical scavenging, ferric reducing power and β-carotene-linoleic acid model system, the anti-HIV-1 reverse transcriptase (RT) enzyme inhibitory effects using an ELISA kit and acetylcholinesterase (AChE) enzyme inhibition using the microtitre plate assay. Nine of the herbal mixtures (Umzimba omubi, Umuthi wekukhwehlela ne zilonda, Mvusa ukunzi, Umpatisa inko...

  19. Inhibition of acetylcholinesterase activity by essential oil from Citrus paradisi.

    Miyazawa, M; Tougo, H; Ishihara, M

    2001-01-01

    Inhibition of acetylcholinesterase (AChE) activity by essential oils of Citrus paradisi (grapefruit pink in USA) was studied. Inhibition of AChE was measured by the colorimetric method. Nootkatone and auraptene were isolated from C. paradisi oil and showed 17-24% inhibition of AChE activity at the concentration of 1.62 microg/mL. PMID:11858553

  20. The Effects of Exercise-induced Fatigue on Acetylcholinesterase Expression and Activity at Rat Neuromuscular Junctions

    Wen, Guo; Hui, Wang; Dan, Chen; Xiao-Qiong, Wu; Jian-Bin, Tong; Chang-Qi, Li; De-Liang, Lei; Wei-Jun, Cai; Zhi-Yuan, Li; Xue-Gang, Luo

    2009-01-01

    Acetylcholinesterase is the enzyme that terminates neurotransmission by hydrolyzing the acetylcholine released by the motoneurons at the neuromuscular junctions. Although acetylcholinesterase has been studied for almost a century, the underlying relationship between exercise-induced fatigue and acetylcholinesterase activity at the synaptic cleft is not clear. The purpose of this study was to assess the effects of exercise-induced fatigue on the expression and activity of acetylcholinesterase ...

  1. Inhibitory and enzyme-kinetic investigation of chelerythrine and lupeol isolated from Zanthoxylum rhoifolium against krait snake venom acetylcholinesterase

    Ahmad, Mustaq, E-mail: mushtaq213@yahoo.com [University of Science and Technology, Bannu, (Pakistan). Department of Biotechnology; Weber, Andrea D.; Zanon, Graciane; Tavares, Luciana de C.; Ilha, Vinicius; Dalcol, Ionara I.; Morel, Ademir F., E-mail: ademirfariasm@gmail.com [Universidade Federal de Santa Maria, RS (Brazil). Dept. de Quimica

    2014-01-15

    The in vitro activity of chelerythrine and lupeol, two metabolites isolated from Zanthoxylum rhoifolium were studied against the venom of the snake Bungarus sindanus (Elapidae). The venom, which is highly toxic to humans, consists mainly by the enzyme acetylcholinesterase (AChE). Both compounds showed activity against the venom, and the alkaloid chelerythrine presented higher activity than did triterpene lupeol. (author)

  2. Inhibitory and enzyme-kinetic investigation of chelerythrine and lupeol isolated from Zanthoxylum rhoifolium against krait snake venom acetylcholinesterase

    The in vitro activity of chelerythrine and lupeol, two metabolites isolated from Zanthoxylum rhoifolium were studied against the venom of the snake Bungarus sindanus (Elapidae). The venom, which is highly toxic to humans, consists mainly by the enzyme acetylcholinesterase (AChE). Both compounds showed activity against the venom, and the alkaloid chelerythrine presented higher activity than did triterpene lupeol. (author)

  3. Scapaundulin C, a novel labdane diterpenoid isolated from Chinese liverwort Scapania undulate, inhibits acetylcholinesterase activity.

    Kang, Ya-Qi; Zhou, Jin-Chuan; Fan, Pei-Hong; Wang, Shu-Qi; Lou, Hong-Xiang

    2015-12-01

    In the present study, scapaundulin C (1), a new labdane diterpenoid, and four related known compounds scapaundulin A (2), 5α, 8α, 9α-trihydroxy-13E-labden-12-one (3), 5α, 8α-dihydroxy-13E-labden-12-one (4), and (13S)-15-hydroxylabd-8 (17)-en-19-oic acid (5), were isolated from the Chinese liverwort Scapania undulate (L.) Dum., using column chromatography. The structures of these compounds were determined on the basis of 1D- and 2D-NMR analyses. The acetylcholinesterase (AchE) inhibitory activity was evaluated using a bioautographic TLC assay and the cytotoxic activity was evaluated by the MTT method. All the compounds were reported for the first time to exhibit moderate AchE inhibitory activity with minimal inhibitory quantities ranging from 250 to 500 ng. All the compounds were tested for their cytotoxicity against five human tumor cell lines, A549, K562, A2780, Hela, and HT29, and compounds 3 and 4 exhibited moderate inhibitory effects on the growth of A2780 cells. PMID:26721712

  4. Development of translationally active mRNA for larval muscle acetylcholinesterase during ascidian embryogenesis.

    Meedel, T H; Whittaker, J R

    1983-01-01

    Relative quantities of translationally active acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7) mRNA present at various developmental stages were compared in embryos of the ascidian Ciona intestinalis. Purified RNA was tested for its translational capacity by microinjection into Xenopus laevis oocytes; the acetylcholinesterase produced was immunoprecipitated with antibody to Ciona acetylcholinesterase and enzyme activity was assayed radiometrically. With this protocol, enzyme s...

  5. Acetylcholinesterase Modulates Presenilin-1 Levels and γ-Secretase Activity

    Campanari, María-Letizia; García Ayllón, María Salud; Belbin, Olivia; Galcerán, Joan; Lleó, Alberto; Sáez-Valero, Javier

    2014-01-01

    The cholinergic enzyme acetylcholinesterase (AChE) and the catalytic component of the ¿-secretase complex, presenilin-1 (PS1), are known to interact. In this study, we investigate the consequences of AChE-PS1 interactions, particularly the influence of AChE in PS1 levels and ¿-secretase activity. PS1 is able to co-immunoprecipitate all AChE variants (AChE-R and AChE-T) and molecular forms (tetramers and light subunits) present in the human brain. Overexpression of AChE-R or AChE-T, or their r...

  6. Induction of plasma acetylcholinesterase activity in mice challenged with organophosphorus poisons

    The restoration of plasma acetylcholinesterase activity in mice following inhibition by organophosphorus pesticides and nerve agents has been attributed to synthesis of new enzyme. It is generally assumed that activity levels return to normal, are stable and do not exceed the normal level. We have observed over the past 10 years that recovery of acetylcholinesterase activity levels in mice treated with organophosphorus agents (OP) exceeds pretreatment levels and remains elevated for up to 2 months. The most dramatic case was in mice treated with tri-cresyl phosphate and tri-ortho-cresyl phosphate, where plasma acetylcholinesterase activity rebounded to a level 250% higher than the pretreatment activity. The present report summarizes our observations on plasma acetylcholinesterase activity in mice treated with chlorpyrifos, chlorpyrifos oxon, diazinon, tri-ortho-cresyl phosphate, tri-cresyl phosphate, tabun thiocholine, parathion, dichlorvos, and diisopropylfluorophosphate. We have developed a hypothesis to explain the excess acetylcholinesterase activity, based on published observations. We hypothesize that acetylcholinesterase activity is induced when cells undergo apoptosis and that consequently there is a rise in the level of plasma acetylcholinesterase. - Highlights: → Acetylcholinesterase activity is induced by organophosphorus agents. → AChE induction is related to apoptosis. → Induction of AChE activity by OP is independent of BChE.

  7. Anticholinesterase inhibitory activity of quaternary alkaloids from Tinospora crispa.

    Yusoff, Mashitah; Hamid, Hazrulrizawati; Houghton, Peter

    2014-01-01

    Quaternary alkaloids are the major alkaloids isolated from Tinospora species. A previous study pointed to the necessary presence of quaternary nitrogens for strong acetylcholinesterase (AChE) inhibitory activity in such alkaloids. Repeated column chromatography of the vine of Tinospora crispa extract led to the isolation of one new protoberberine alkaloid, 4,13-dihydroxy-2,8,9-trimethoxydibenzo[a,g]quinolizinium (1), along with six known alkaloids-dihydrodiscretamine (2), columbamine (3), magnoflorine (4), N-formylannonaine (5), N-formylnornuciferine (6), and N-trans-feruloyltyramine (7). The seven compounds were isolated and structurally elucidated by spectroscopic analysis. Two known alkaloids, namely, dihydrodiscretamine and columbamine are reported for the first time for this plant. The compounds were tested for AChE inhibitory activity using Ellman's method. In the AChE inhibition assay, only columbamine (3) showed strong activity with IC50 48.1 µM. The structure-activity relationships derived from these results suggest that the quaternary nitrogen in the skeleton has some effect, but that a high degree of methoxylation is more important for acetylcholinesterase inhibition. PMID:24448061

  8. Anticholinesterase Inhibitory Activity of Quaternary Alkaloids from Tinospora crispa

    Mashitah Yusoff

    2014-01-01

    Full Text Available Quaternary alkaloids are the major alkaloids isolated from Tinospora species. A previous study pointed to the necessary presence of quaternary nitrogens for strong acetylcholinesterase (AChE inhibitory activity in such alkaloids. Repeated column chromatography of the vine of Tinospora crispa extract led to the isolation of one new protoberberine alkaloid, 4,13-dihydroxy-2,8,9-trimethoxydibenzo[a,g]quinolizinium (1, along with six known alkaloids—dihydrodiscretamine (2, columbamine (3, magnoflorine (4, N-formylannonaine (5, N-formylnornuciferine (6, and N-trans-feruloyltyramine (7. The seven compounds were isolated and structurally elucidated by spectroscopic analysis. Two known alkaloids, namely, dihydrodiscretamine and columbamine are reported for the first time for this plant. The compounds were tested for AChE inhibitory activity using Ellman’s method. In the AChE inhibition assay, only columbamine (3 showed strong activity with IC50 48.1 µM. The structure–activity relationships derived from these results suggest that the quaternary nitrogen in the skeleton has some effect, but that a high degree of methoxylation is more important for acetylcholinesterase inhibition.

  9. Interleukin 6 modulates acetylcholinesterase activity of brain neurons

    Classically, radiation injuries results in a peripheral inflammatory process, and we have previously observed an early systemic interleukin 6 (IL-6) release following whole-body irradiation. Besides, we have demonstrated an early decrease of rat or primate brain acetylcholinesterase (AChE) activity a gamma exposure. The object of the present study is to find possible IL-6 systemic effects on the brain AChE activity. We show that, though intravenous (i.v.) or intra-cerebro-ventricular (ICV) injection of IL-6 can induce a drop in rat brain AChE activity, this cytokine induces only a slight decrease of the AChE release in cultured brain cells. (author)

  10. Effect of fluorocarbons on acetylcholinesterase activity and some counter measures

    Young, W.; Parker, J. A.

    1975-01-01

    An isolated vagal sympathetic heart system has been successfully used for the study of the effect of fluorocarbons (FCs) on cardiac performance and in situ enzyme activity. Dichlorodifluoromethane sensitizes this preparation to sympathetic stimulation and to exogenous epinephrine challenge. Partial and complete A-V block and even cardiac arrest have been induced by epinephrine challenge in the FC sensitized heart. Potassium chloride alone restores the rhythmicity but not the normal contractility of the heart in such a situation. Addition of glucose will, however, completely restore the normal function of the heart which is sensitized by dichlorodifluoromethane. The ED 50 values of acetylcholinesterase activity which are used as a measure of relative effectiveness of fluorocarbons are compared with the maximum permissible concentration. Kinetic studies indicate that all the fluorocarbons tested so far are noncompetitive.

  11. Finding of polysaccharide-peptide complexes in Cordyceps militaris and evaluation of its acetylcholinesterase inhibition activity

    Cheng-Han Tsai

    2015-03-01

    Full Text Available Acetylcholinesterase (AChE inhibition enhances learning and cognitive ability for treatment of Alzheimer's disease. Polysaccharide–peptide complexes were identified in Cordyceps militaris (CPSPs and characterized for their AChE inhibitory properties. Three polymers (CPSP-F1, -F2, and -F3 were extracted and separated by ultrasound-assisted extraction and diethylaminoethanol (DEAE–Sepharose CL-6B column chromatography. Polysaccharide–peptide complexes were identified by DEAE–Sepharose CL-6B column chromatography and high-performance gel-filtration chromatography, Fourier transform infrared spectra, amino sugar composition analysis, and β-elimination reaction to identify polysaccharide–peptide bond categories. Separation of CPSP can increase AChE inhibitory activity from the crude polysaccharide of C. militaris. CPSP-F1 and CPSP-F2 exhibited half maximal inhibitory concentrations of 32.2 ± 0.2 mg/mL and 5.3 ± 0.0 mg/mL. Thus, we identified polysaccharide–peptide complexes from C. militaris and suggest CPSP has great potential in AChE inhibition bioassay.

  12. Sub-acute Toxicity of Carbofuran on Acetylcholinesterase Activity in the Freshwater Catfish, Clarias batrachus

    2005-01-01

    The inhibition of acetylcholinesterase (ACHE) activity has been widely used as a biomarker in an animal exposed to the pesticides. However, the interaction of extensively used organocarbamate insecticide, carbofuran, with the nervous system of the aquatic organisms is not properly studied. AChE is a key enzyme which catalyses the hydrolysis of acetylcholine, a neurotransmitter at the neuromuscular junctions, and thus regulates the neurotransmission system. In the present study, we have evaluated the impact of sub-acute concentrations (0.01 and 0.02 mg/L i.e. 1/20th and 1/10th of LC50) of carbofuran on the activity of acetylcholinesterase,from different tissues of Clarias batrachus, a fresh water teleost, after 96 hr and 15 days exposure periods in vivo. The carbofuran significantly reduced the activity of AChE in different tissues of C. batrachus at both concentrations and periods of exposure. The greater inhibition of AChE activities were recorded in fish tissues at higher carbofuran concentration (0.02 mg/L) after longer (15days) treatment period. The inhibition of AChE activity in all fish tissues tested was dependent on pesticide concentration and the duration of treatment. AChE from the tissues of C. batrachus was found to be a true cholinesterase as it was completely inhibited by the small concentration (nM) of eserine as tested in vitro. It was found that carbofuran at very low concentration exerted significant inhibitory effect on AChE activity in fish tissues.

  13. Synthesis, Characterization, Acetylcholinesterase Inhibition, Molecular Modeling and Antioxidant Activities of Some Novel Schiff Bases Derived from 1-(2-Ketoiminoethylpiperazines

    A. Hamid A. Hadi

    2011-11-01

    Full Text Available Some novel Schiff bases derived from 1-(2-ketoiminoethylpiperazines were synthesized and characterized by mass spectroscopy, FTIR, UV-Visible, 1H and 13C-NMR. The compounds were tested for inhibitory activities on human acetylcholinesterase (hAChE, antioxidant activities, acute oral toxicity and further studied by molecular modeling techniques. The study identified the compound (DHP to have the highest activity among the series in hAChE inhibition and DPPH assay while the compound LP revealed the highest activity in the FRAP assay. The hAChE inhibitory activity of DHP is comparable with that of propidium, a known AChE inhibitor. This high activity of DHP was checked by molecular modeling which showed that DHP could not be considered as a bivalent ligand due to its incapability to occupy the esteratic site (ES region of the 3D crystal structure of hAChE. The antioxidant study unveiled varying results in 1,1-diphenyl-1-picrylhydrazyl (DPPH and ferric reducing antioxidant power (FRAP assays. This indicates mechanistic variations of the compounds in the two assays. The potential therapeutic applications and safety of these compounds were suggested for use as human acetylcholinesterase inhibitors and antioxidants.

  14. Plant-derived acetylcholinesterase inhibitory alkaloids for the treatment of Alzheimer's disease

    Dall'Acqua S

    2013-01-01

    Full Text Available Stefano Dall'AcquaDepartment of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, ItalyAbstract: The inhibition of acetylcholinesterase (AChE has been one of the most used strategies for the treatment of Alzheimer's disease (AD. The AChE inhibitors (AChE-I produce not only short-term symptomatic effects, but can also play a role in other pathological mechanisms of the disease (eg, formation of amyloid-β plaques, which has renewed interest in the discovery of such inhibitors. Four of the five currently prescribed treatments for AD are AChE-I. Natural alkaloids such as galantamine or alkaloid-related synthetic compounds (such as rivastigmine are considered beneficial for patients with mild-to-moderate AD. However, there is a need for the discovery of more effective compounds and for this reason, plants can still be a potential source of new AChE-I. Findings and advances in knowledge about natural alkaloids as potential new drugs acting as AChE-I will be summarized in this paper.Keywords: quinolizidine, steroidal, indole, isoquinoline

  15. IN VITRO INHIBITION OF ACETYLCHOLINESTERASE ACTIVITY IN HUMAN RED BLOOD CELLS BY CADMIUM AND LEAD

    Abdollahi, M.; M. Biukabadi M. A. Ebrahimzadeh

    1998-01-01

    The effects of cadmium and lead on human erythrocyte acetylcholinesterase activity were studied. Blood used in this study was obtained from 24 healthy individuals, then after hemolysation, treated with 3 various concentrations of cadmium and lead. A strong inhibition of acetylcholinesterase was noted in treated samples by cadmium and lead. The remaining activity In the case of lead, the remaining activity was found to be 81% with the highest concentration , S7% with the middle and 94% with th...

  16. EEG SPECTRA, BEHAVIORAL STATES AND MOTOR ACTIVITY IN RATS EXPOSED TO ACETYLCHOLINESTERASE INHIBITOR CHLORPYRIFOS.

    Exposure to organophosphate pesticides (OP) has been associated with sleep disorders: insomnia and ?excessive dreaming'. However neuronal mechanisms of these effects have not been analyzed. OP inhibit acetylcholinesterase activity leading to a hyperativity of the brain cholin...

  17. Degree of inhibition of cortical acetylcholinesterase activity and cognitive effects by donepezil treatment in Alzheimer's disease

    Bohnen, N; Kaufer, D; Hendrickson, R; Ivanco, L; Lopresti, B; Koeppe, R; Meltzer, C; Constantine, G; Davis, J.; Mathis, C.; DeKosky, S; Moore, R.

    2005-01-01

    Objectives: To determine in vivo cortical acetylcholinesterase (AChE) activity and cognitive effects in subjects with mild Alzheimer's disease (AD, n = 14) prior to and after 12 weeks of donepezil therapy.

  18. Flavanone glycosides as acetylcholinesterase inhibitors: Computational and experimental evidence

    C Remya

    2014-01-01

    Full Text Available Acetylcholinesterase hydrolyzes the neurotransmitter called acetylcholine and is crucially involved in the regulation of neurotransmission. One of the observable facts in the neurodegenerative disorders like Alzheimer′s disease is the decrease in the level of acetylcholine. Available drugs that are used for the treatment of Alzheimer′s disease are primarily acetylcholinesterase inhibitors with multiple activities. They maintain the level of acetylcholine in the brain by inhibiting the acetylcholinesterase function. Hence acetylcholinesterase inhibitors can be used as lead compounds for the development of drugs against AD. In the present study, the binding potential of four flavanone glycosides such as naringin, hesperidin, poncirin and sakuranin against acetylcholinesterase was analysed by using the method of molecular modeling and docking. The activity of the top scored compound, naringin was further investigated by enzyme inhibition studies and its inhibitory concentration (IC 50 towards acetylcholinesterase was also determined.

  19. Phenolic Lipids Affect the Activity and Conformation of Acetylcholinesterase from Electrophorus electricus (Electric eel)

    Maria Stasiuk; Alicja Janiszewska; Arkadiusz Kozubek

    2014-01-01

    Phenolic lipids were isolated from rye grains, cashew nutshell liquid (CNSL) from Anacardium occidentale, and fruit bodies of Merrulius tremellosus, and their effects on the electric eel acetylcholinesterase activity and conformation were studied. The observed effect distinctly depended on the chemical structure of the phenolic lipids that were available for interaction with the enzyme. All of the tested compounds reduced the activity of acetylcholinesterase. The degree of inhibition varied, ...

  20. Quantitative and Qualitative Changes in the Skeletal Muscle Acetylcholinesterase Activity of Oreochromis niloticus Exposed to Methylparathion

    Elena Catap; Glorina Pocsidio

    1994-01-01

    Spectrophotometric assays and histochemical tests for acetylcholinesterase activity in the epaxial skeletal muscle of maturing Oreochromis niloticus after in-vivo exposure to 0.10 mg/L methylparathion showed significant inhibition of the enzyme by the pesticide. The assays manifested enzyme inhibition, after 48 and 96 hours of exposure, of 43.19% and 56.62%, respectively. These results were confirmed by the occurrences of decreased sites of acetylcholinesterase activity in the muscle fibers a...

  1. Kolaviron, isolated from Garcinia kola, inhibits acetylcholinesterase activities in the hippocampus and striatum of wistar rats

    Ijomone, Omamuyovwi M.; Obi, Augustine U.

    2013-01-01

    Background Kolaviron, isolated from seeds of Garcinia kola, have been shown to possess wide pharmacological properties. Purpose The present study examined the effect of kolaviron on acetylcholinesterase activities in the hippocampus and striatum of adult Wistar rats. Methods In this study, histological and histochemical methods were used to investigate the effects of kolaviron on the histology of the hippocampus and striatum and on acetylcholinesterase activities in these brain regions. Resul...

  2. Simultaneous ultrastructural visualization of acetylcholinesterase activity and tritiated norepinephrine uptake in renal nerves

    In this investigation we have combined the methods of ultrastructural demonstration of acetylcholinesterase activity with electron microscopic autoradiography for the demonstration of norepinephrine uptake. The results show electron-dense deposits indicative of acetylcholinesterase activity associated with perivascular axons overlaid by concentrations of silver grains representing exogenous tritiated norepinephrine. Forty-five percent of the intervaricose regions and 19% of the varicosities overlaid by autoradiographic grains showed ''moderate'' amounts of cholinesterase staining. A greater proportion of autoradiographic grains was observed on the varicosities than in the intervaricose regions; however, the amount of acetylcholinesterase activity was greater in the intervaricose regions than in the varicosities. This investigation provides evidence for the presence of periaxonal acetylcholinesterase staining in adrenergic axons in the rat kidney

  3. Assay of Acetylcholinesterase Activity and Electrochemical Determination of Fenthion in Oil-in-water Emulsion

    Sun Kai; He JingJing; Miao YuQing

    2009-01-01

    @@ Organophosphates (OPs) have been widely used as pesticides,insecticides or even chemical warfare agents.Acetylcholinesterase (ACHE) inhibition has been employed to develop verious assay methods for detection of pesticides with the advantages of low cost,simple procedure and quick assay time.The study of acetylcholinesterase (ACHE) activity and OPs inhibition in the solution containing organic solvent is extremely important owing to poor solubility of Ops in water and a higher solubility in organic solvents.

  4. Activity Dependent Regulation of Inhibitory Circuitry

    Sharma, Nikhil

    2015-01-01

    Inhibition controls information flow through a neural circuit by modulating synaptic integration, restricting action potentials, and coordinating the activity of ensembles of neurons. These functions are mediated by a diverse array of inhibitory neuron subtypes that synapse on defined domains of a postsynaptic neuron. Activity-dependent transcription controls inhibitory synapse number and function, but how this transcription program affects the inhibitory inputs that form on di...

  5. Changes of acetylcholinesterase activity in different brain areas of the rat following head irradiation

    Changes of acetylcholinesterase activity in rat hemispheres, brainstem, cerebellum and pontomedullar part following irradiation of the head with 7.0 Gy and 20.0 Gy, resp., were studied. The activity was increased after irradiation; the greatest changes of activity were observed in the hemispheres from the 2nd to the 7th day after irradiation and no changes in the cerebellum were detected. The acetylcholinesterase activity reached the normal level 10-30 days after irradiation. These results suggest that local irradiation of the head, beside other changes, caused a damage of the central cholinergic function. (author)

  6. Quantitative and Qualitative Changes in the Skeletal Muscle Acetylcholinesterase Activity of Oreochromis niloticus Exposed to Methylparathion

    Elena Catap

    1994-12-01

    Full Text Available Spectrophotometric assays and histochemical tests for acetylcholinesterase activity in the epaxial skeletal muscle of maturing Oreochromis niloticus after in-vivo exposure to 0.10 mg/L methylparathion showed significant inhibition of the enzyme by the pesticide. The assays manifested enzyme inhibition, after 48 and 96 hours of exposure, of 43.19% and 56.62%, respectively. These results were confirmed by the occurrences of decreased sites of acetylcholinesterase activity in the muscle fibers as exhibited upon performance of histochemical tests.

  7. Effect of X-irradiation on acetylcholinesterase activity in the brain of mouse Mus booduga

    Acetylcholinesterase (AChE; E.C. 1.1.7) activity in the brain of lethally X-irradiated mouse, Mus booduga decreased progressively from 2 hours to 5 days of post-irradiation periods. A general loss of affinity to substrate during early days of post-irradiation, and a subsequent tendency towards normalization were noticed. (auth.)

  8. Chlorpyrifos and chlorpyrifos-oxon inhibit axonal growth by interfering with the morphogenic activity of acetylcholinesterase

    A primary role of acetylcholinesterase (AChE) is regulation of cholinergic neurotransmission by hydrolysis of synaptic acetylcholine. In the developing nervous system, however, AChE also functions as a morphogenic factor to promote axonal growth. This raises the question of whether organophosphorus pesticides (OPs) that are known to selectively bind to and inactivate the enzymatic function of AChE also interfere with its morphogenic function to perturb axonogenesis. To test this hypothesis, we exposed primary cultures of sensory neurons derived from embryonic rat dorsal root ganglia (DRG) to chlorpyrifos (CPF) or its oxon metabolite (CPFO). Both OPs significantly decreased axonal length at concentrations that had no effect on cell viability, protein synthesis or the enzymatic activity of AChE. Comparative analyses of the effects of CPF and CPFO on axonal growth in DRG neurons cultured from AChE nullizygous (AChE-/-) versus wild type (AChE+/+) mice indicated that while these OPs inhibited axonal growth in AChE+/+ DRG neurons, they had no effect on axonal growth in AChE-/- DRG neurons. However, transfection of AChE-/- DRG neurons with cDNA encoding full-length AChE restored the wild type response to the axon inhibitory effects of OPs. These data indicate that inhibition of axonal growth by OPs requires AChE, but the mechanism involves inhibition of the morphogenic rather than enzymatic activity of AChE. These findings suggest a novel mechanism for explaining not only the functional deficits observed in children and animals following developmental exposure to OPs, but also the increased vulnerability of the developing nervous system to OPs

  9. IN VITRO INHIBITION OF ACETYLCHOLINESTERASE ACTIVITY IN HUMAN RED BLOOD CELLS BY CADMIUM AND LEAD

    M. Abdollahi

    1998-08-01

    Full Text Available The effects of cadmium and lead on human erythrocyte acetylcholinesterase activity were studied. Blood used in this study was obtained from 24 healthy individuals, then after hemolysation, treated with 3 various concentrations of cadmium and lead. A strong inhibition of acetylcholinesterase was noted in treated samples by cadmium and lead. The remaining activity In the case of lead, the remaining activity was found to be 81% with the highest concentration , S7% with the middle and 94% with the lowest one (30 fi g/dl, p<0.05. Cadmium showed a nearly linear correlation between doses used and decrease in activity (r- = 0.S3, lead showed a better correlation (r- = 0.92. The direct effect of metal ions on AChE, i.e. a decrease in quantity of the enzyme, may be a proposed mechanism for this depression.

  10. Intracerebroventricular D-galactose administration impairs memory and alters activity and expression of acetylcholinesterase in the rat.

    Rodrigues, André Felipe; Biasibetti, Helena; Zanotto, Bruna Stela; Sanches, Eduardo Farias; Pierozan, Paula; Schmitz, Felipe; Parisi, Mariana Migliorini; Barbé-Tuana, Florencia; Netto, Carlos Alexandre; Wyse, Angela T S

    2016-05-01

    Tissue accumulation of galactose is a hallmark in classical galactosemia. Cognitive deficit is a symptom of this disease which is poorly understood. The aim of this study was to investigate the effects of intracerebroventricular administration of galactose on memory (inhibitory avoidance and novel object recognition tasks) of adult rats. We also investigated the effects of galactose on acetylcholinesterase (AChE) activity, immunocontent and gene expression in hippocampus and cerebral cortex. Wistar rats received a single injection of galactose (4mM) or saline (control). For behavioral parameters, galactose was injected 1h or 24h previously to the testing. For biochemical assessment, animals were decapitated 1h, 3h or 24h after galactose or saline injection; hippocampus and cerebral cortex were dissected. Results showed that galactose impairs the memory formation process in aversive memory (inhibitory avoidance task) and recognition memory (novel object recognition task) in rats. The activity of AChE was increased, whereas the gene expression of this enzyme was decreased in hippocampus, but not in cerebral cortex. These findings suggest that these changes in AChE may, at least in part, to lead to memory impairment caused by galactose. Taken together, our results can help understand the etiopathology of classical galactosemia. PMID:26948151

  11. Brain acetylcholinesterase activity is markedly reduced in dominantly-inherited olivopontocerebellar atrophy.

    Kish, S J; Schut, L; Simmons, J.; Gilbert, J.; Chang, L. J.; Rebbetoy, M

    1988-01-01

    The activity was measured of the acetylcholine catabolising enzyme acetylcholinesterase (AChE) in brain after necropsy of seven patients from one established pedigree with dominantly-inherited olivopontocerebellar atrophy (OPCA), a cerebellar ataxia disorder in which neuropathological changes are assumed to be primarily restricted to cerebellum, lower brain stem and spinal cord. Mean AChE activity was significantly reduced in cerebral (-51% to 65%) and cerebellar (-47%) cortex with a less sev...

  12. Determination of Acetylcholinesterase activities in marine gastropod (Morula granulata) as a biomarker of neurotoxic contaminants along the Goan coast.

    Sarkar, A.; Tegur, P.M.; Jana, S.; Rao, P.V.S.S.D.P.

    Acetylcholinesterase (AChE) is an enzyme that degrades the neurotransmitter acetylcholine, producing choline and acetate. group. It is mainly found at neuromuscular junctions and cholinergic synapses in the central nervous system, where its activity...

  13. In situ monitoring of myenteric neuron activity using acetylcholinesterase-modified AlGaN/GaN solution-gate field-effect transistors.

    Müntze, Gesche Mareike; Pouokam, Ervice; Steidle, Julia; Schäfer, Wladimir; Sasse, Alexander; Röth, Kai; Diener, Martin; Eickhoff, Martin

    2016-03-15

    The response characteristics of acetylcholinesterase-modified AlGaN/GaN solution-gate field-effect transistors (AcFETs) are quantitatively analyzed by means of a kinetic model. The characterization shows that the covalent enzyme immobilization process yields reproducible AcFET characteristics with a Michaelis constant KM of (122 ± 4) μM for the immobilized enzyme layer. The increase of KM by a factor of 2.4 during the first four measurement cycles is attributed to partial denaturation of the enzyme. The AcFETs were used to record the release of acetylcholine (ACh) by neuronal tissue cultivated on the gate area upon stimulation by rising the extracellular K(+) concentration. The neuronal tissue constituted of isolated myenteric neurons from four to 12 days old Wistar rats, or sections from the muscularis propria containing the myenteric plexus from adult rats. For both cases the AcFET response was demonstrated to be related to the activity of the immobilized acetylcholinesterase using the reversible acetylcholinesterase blocker donepezil. A concentration response curve of this blocking agent revealed a half maximal inhibitory concentration of 40 nM which is comparable to values measured by complementary in vitro methods. PMID:26547432

  14. Effects of oximes on muscle force and acetylcholinesterase activity in isolated mouse hemidiaphragms exposed to paraoxon

    Toxicity of organophosphates (OP) is caused by inhibition of acetylcholinesterase (AChE), resulting in accumulation of acetylcholine. While cholinolytics such as atropine are able to counteract muscarinic symptoms, they are unable to restore the impaired neuromuscular transmission (NMT). Here, oximes as potential reactivators of inhibited AChE may be effective. Until now, no unequivocal relation between oxime-induced increase in muscle force and reactivation has been demonstrated. To address this issue the isolated circumfused mouse hemidiaphragm was used as an experimental model. The muscle force generation upon tetanic stimuli was recorded during AChE inhibition by 1 μM paraoxon and after a wash-out period in the presence of obidoxime, pralidoxime and the experimental oximes HI 6, and HLoe 7, 10 μM each. At the end of the experiments AChE activity was determined in the diaphragm homogenates by a radiometric assay. At 50-Hz stimulation, recovery was complete with obidoxime, nearly complete with HLoe 7 but incomplete with HI 6 and pralidoxime. Only with obidoxime a significant increase in AChE activity was found. An increase of AChE to 10% of normal was sufficient to allow normal muscle force generation. When paraoxon was still present, obidoxime and HLoe 7 were effective at 0.1 μM paraoxon, but failed so at paraoxon >1 μM. The data show different effectiveness of the oximes investigated in reactivation of muscle AChE and recovery of NMT after inhibition by paraoxon. Although an increase in muscle force by the oximes was accompanied by a measurable increase in AChE activity only in the case of obidoxime, the plot of muscle force against AChE activity as well as lacking evidence for a direct effect and adaptive processes indicate that reactivation of the enzyme is the main mechanism of NMT recovery. In agreement, in presence of AChE inhibitory concentrations of paraoxon during reactivation a reduced effectiveness of oximes was found

  15. Phytochemicals Content, Antioxidant Activity and Acetylcholinesterase Inhibition Properties of Indigenous Garcinia parvifolia Fruit

    Siti Hawa Ali Hassan; FRY, Jeffrey R.; Mohd Fadzelly Abu Bakar

    2013-01-01

    Garcinia parvifolia belongs to the same family as mangosteen (Garcinia mangostana), which is known locally in Sabah as “asam kandis” or cherry mangosteen. The present study was conducted to determine the phytochemicals content (total phenolic, flavonoid, anthocyanin, and carotenoid content) and antioxidant and acetylcholinesterase inhibition activity of the flesh and peel of G. parvifolia. All samples were freeze-dried and extracted using 80% methanol and distilled water. For the 80% methanol...

  16. Synthesis of Novel Chalcones as Acetylcholinesterase Inhibitors

    Thanh-Dao Tran

    2016-07-01

    Full Text Available A new series of benzylaminochalcone derivatives with different substituents on ring B were synthesized and evaluated as inhibitors of acetylcholinesterase. The study is aimed at identification of novel benzylaminochalcones capable of blocking acetylcholinesterase activity for further development of an approach to Alzheimer’s disease treatment. These compounds were produced in moderate to good yields via Claisen-Schmidt condensation and subjected to an in vitro acetylcholinesterase inhibition assay, using Ellman’s method. The in silico docking procedure was also employed to identify molecular interactions between the chalcone compounds and the enzyme. Compounds with ring B bearing pyridin-4-yl, 4-nitrophenyl, 4-chlorophenyl and 3,4-dimethoxyphenyl moieties were discovered to exhibit significant inhibitory activities against acetylcholinesterase, with IC50 values ranging from 23 to 39 µM. The molecular modeling studies are consistent with the hypothesis that benzylaminochalcones could exert their effects as dual-binding-site acetylcholinesterase inhibitors, which might simultaneously enhance cholinergic neurotransmission and inhibit β-amyloid aggregation through binding to both catalytic and peripheral sites of the enzyme. These derivatives could be further developed to provide novel leads for the discovery of new anti-Alzheimer drugs in the future.

  17. Enzyme inhibitory activity of selected Philippine plants

    In the Philippines, the number one cause of death are cardiovascular diseases. Diseases linked with inflammation are proliferating. This research aims to identify plant extracts that have potential activity of cholesterol-lowering, anti-hypertension, anti-gout, anti-inflammatory and fat blocker agents. Although there are commercially available drugs to treat the aforementioned illnesses, these medicine have adverse side-effects, aside from the fact that they are expensive. The results of this study will serve as added knowledge to contribute to the development of cheaper, more readily available, and effective alternative medicine. 100 plant extracts from different areas in the Philippines have been tested for potential inhibitory activity against Hydroxymethylglutaryl-coenzyme A (HMG-CoA), Lipoxygenase, and Xanthine Oxidase. The plant samples were labeled with codes and distributed to laboratories for blind testing. The effective concentration of the samples tested for Xanthine oxidase is 100 ppm. Samples number 9, 11, 14, 29, 43, 46, and 50 have shown significant inhibitory activity at 78.7%, 78.4%, 70%, 89.2%, 79%, 67.4%, and 67.5% respectively. Samples tested for Lipoxygenase inhibition were set at 33ppm. Samples number 2, 37, 901, 1202, and 1204 have shown significant inhibitory activity at 66, 84.9%, 88.55%, 93.3%, and 84.7% respectively. For HMG-CoA inhibition, the effective concentration of the samples used was 100 ppm. Samples number 1 and 10 showed significant inhibitory activity at 90.1% and 81.8% respectively. (author)

  18. Histochemical diagnosis of Hirschsprung's disease and a comparison of the histochemical and biochemical activity of acetylcholinesterase in rectal mucosal biopsies.

    Patrick, W. J.; Besley, G T; Smith, I. I.

    1980-01-01

    Three hundred and seventy-two rectal mucosal biopsies, taken from 150 children and young adults with chronic constipation, were subjected to histochemical and biochemical analysis of acetylcholinesterase to excude Hirschsprung's disease. The relative merits of the procedures were compared. The histochemical method was considered to be the most practical for laboratories handling small numbers of biopsies but the biochemical estimation of acetylcholinesterase activity was found to be a useful ...

  19. Studies on the effects of some insecticides on the brain acetylcholinesterase activity of Tilapia zilli in two treated tropical rivers

    With a view to controlling onchocerciasis in West Africa, the Marahoue and Black Volta Rivers in Cote d'Ivoire were treated with chlorphoxim and temephos, respectively, at a concentration of 0.5 mg·L-1 per 10 minute application to kill the Simulium larvae. As part of the Onchocerciasis Control Programme, studies were conducted with caged Tilapia zilli to determine the effects of the two larvicides on the fishery resources in the treated rivers. These showed that chlorphoxim inhibits the brain acetylcholinesterase (AChE) activity of the caged T. zilli up to 1 km downstream of the breeding site. The highest level of reduction in AChE activity (32%) was recorded in the caged fish placed near the point of release of the chlorphoxim 24 hours after the river treatment. At 0.5 km downstream of the breeding site, the percentage enzyme reduction was 24%, and at the 1 km point the AChE activity was reduced by 17%. There was no significant reduction (P > 0.05) in the brain enzyme activity of the caged fish placed at a distance of about 3 km downstream of the breeding site. It was further observed that the caged fish had not recovered from the inhibitory effects of the chlorphoxim 48 hours after the river treatment. No evidence of any inhibitory effects on the brain AChE activity of the caged fish was found as a result of temephos treatment of the Black Volta River at any distance from the point of larvicide application. (author). 16 refs, 1 fig., 4 tabs

  20. Endosulfan induces changes in spontaneous swimming activity and acetylcholinesterase activity of Jenynsia multidentata (Anablepidae, Cyprinodontiformes)

    Ballesteros, M.L. [Facultad de Ciencias Exactas, Fisicas y Naturales, Catedra Diversidad Animal II, Universidad Nacional de Cordoba, Av. Velez Sarsfield 299, 5000 Cordoba (Argentina); Durando, P.E. [Facultad de Ciencias Exactas, Fisicas y Naturales, Departamento de Biologia, Catedra de Fisiologia Animal, Universidad Nacional de San Juan, Complejo ' Islas Malvinas' , Av. Jose I. de la Roza y Meglioli, Rivadavia, San Juan (Argentina); Nores, M.L. [Facultad de Ciencias Medicas, Universidad Nacional de Cordoba-CONICET, Ciudad Universitaria, Cordoba (Argentina); Diaz, M.P. [Facultad de Ciencias Medicas, Catedra de Estadistica y Bioestadistica, Escuela de Nutricion, Universidad Nacional de Cordoba, Pabellon Chile, Ciudad Universitaria, 5000 Cordoba (Argentina); Bistoni, M.A., E-mail: mbistoni@com.uncor.ed [Facultad de Ciencias Exactas, Fisicas y Naturales, Catedra Diversidad Animal II, Universidad Nacional de Cordoba, Av. Velez Sarsfield 299, 5000 Cordoba (Argentina); Wunderlin, D.A. [Facultad de Ciencias Quimicas, Dto. Bioquimica Clinica-CIBICI, Universidad Nacional de Cordoba-CONICET, Haya de la Torre esq. Medina Allende, Ciudad Universitaria, 5000 Cordoba (Argentina)

    2009-05-15

    We assessed changes in spontaneous swimming activity and acetylcholinesterase (AchE) activity of Jenynsia multidentata exposed to Endosulfan (EDS). Females of J. multidentata were exposed to 0.072 and 1.4 mug L{sup -1} EDS. Average speed and movement percentage were recorded during 48 h. We also exposed females to EDS at five concentrations between 0.072 and 1.4 mug L{sup -1} during 24 h, and measured the AchE activity in brain and muscle. At 0.072 mug L{sup -1} EDS swimming motility decreased relative to the control group after 45 h, while at 1.4 mug L{sup -1} EDS swimming motility decreased after 24 h. AchE activity significantly decreased in muscle when J. multidentata were exposed to EDS above 0.072 mug L{sup -1}, while no significant changes were observed in brain. Thus, changes in swimming activity and AchE activity in muscle are good biomarkers of exposure to EDS in J. multidentata. - This work reports changes observed in spontaneous swimming activity and AchE activity of Jenynsia multidentata exposed to sublethal concentrations of Endosulfan.

  1. Endosulfan induces changes in spontaneous swimming activity and acetylcholinesterase activity of Jenynsia multidentata (Anablepidae, Cyprinodontiformes)

    We assessed changes in spontaneous swimming activity and acetylcholinesterase (AchE) activity of Jenynsia multidentata exposed to Endosulfan (EDS). Females of J. multidentata were exposed to 0.072 and 1.4 μg L-1 EDS. Average speed and movement percentage were recorded during 48 h. We also exposed females to EDS at five concentrations between 0.072 and 1.4 μg L-1 during 24 h, and measured the AchE activity in brain and muscle. At 0.072 μg L-1 EDS swimming motility decreased relative to the control group after 45 h, while at 1.4 μg L-1 EDS swimming motility decreased after 24 h. AchE activity significantly decreased in muscle when J. multidentata were exposed to EDS above 0.072 μg L-1, while no significant changes were observed in brain. Thus, changes in swimming activity and AchE activity in muscle are good biomarkers of exposure to EDS in J. multidentata. - This work reports changes observed in spontaneous swimming activity and AchE activity of Jenynsia multidentata exposed to sublethal concentrations of Endosulfan.

  2. Melanoma inhibitory activity in Brazilian patients with cutaneous melanoma*

    Odashiro, Macanori; Hans Filho, Gunter; Pereira, Patricia Rusa; Castro, Ana Rita Coimbra Motta; Stief, Alcione Cavalheiro; Pontes, Elenir Rose Jardim Cury; Odashiro, Alexandre Nakao

    2015-01-01

    BACKGROUND: Melanoma inhibitory activity is a protein secreted by melanoma cells and has been used as a tumor marker. Increased Melanoma inhibitory activity serum levels are related to metastatic disease or tumor recurrence. Currently there are no studies on Melanoma inhibitory activity and cutaneous melanoma involving Brazilian patients. OBJECTIVE: To evaluate the performance and feasibility of measuring Melanoma inhibitory activity levels in Brazilian patients with cutaneous melanoma. METHO...

  3. Involvement of oxidative stress in the enhancement of acetylcholinesterase activity induced by amyloid beta-peptide

    de Melo, Joana Barbosa; Agostinho, Paula; Oliveira, Catarina Resende

    2003-01-01

    Acetylcholinesterase (AChE) activity is increased within and around amyloid plaques, which are present in Alzheimer's disease (AD) patient's brain. In this study, using cultured retinal cells as a neuronal model, we analyzed the effect of the synthetic peptide A[beta]25-35 on the activity of AChE, the degradation enzyme of acetylcholine, as well as the involvement of oxidative stress in this process. The activity of AChE was increased when retinal cells were incubated with A[beta]25-35 (25 [m...

  4. Effect of Moringa oleifera flower extract on larval trypsin and acetylcholinesterase activities in Aedes aegypti.

    Pontual, Emmanuel Viana; Napoleão, Thiago Henrique; Dias de Assis, Caio Rodrigo; de Souza Bezerra, Ranilson; Xavier, Haroudo Satiro; Navarro, Daniela Maria do Amaral Ferraz; Coelho, Luana Cassandra Breitenbach Barroso; Paiva, Patrícia Maria Guedes

    2012-03-01

    Aedes aegypti control is crucial to reducing dengue fever. Aedes aegypti larvae have developed resistance to organophosporous insecticides and the use of natural larvicides may help manage larval resistance by increasing elements in insecticide rotation programs. Here, we report on larvicidal activity of Moringa oleifera flower extract against A. aegypti L(1), L(2), L(3), and L(4) as well as the effect of flower extract on gut trypsin and whole-larval acetylcholinesterase from L(4.) In addition, the heated flower extract was investigated for larvicidal activity against L(4) and effect on larval gut trypsin. Moringa oleifera flower extract contains a proteinaceous trypsin inhibitor (M. oleifera flower trypsin inhibitor, MoFTI), triterpene (β-amyrin), sterol (β-sitosterol) as well as flavonoids (kaempferol and quercetin). Larvicidal activity was detected against L(2), L(3), and L(4) (LC(50) of 1.72%, 1.67%, and 0.92%, respectively). Flower extract inhibited L(4) gut trypsin (MoFTI K(i) = 0.6 nM) and did not affect acetylcholinesterase activity. In vivo assay showed that gut trypsin activity from L(4) treated with M. oleifera flower extract decreased over time (0-1,440 min) and was strongly inhibited (98.6%) after 310 min incubation; acetylcholinesterase activity was not affected. Thermal treatment resulted in a loss of trypsin inhibitor and larvicidal activities, supporting the hypothesis that flower extract contains a proteinaceous trypsin inhibitor that may be responsible for the deleterious effects on larval mortality. PMID:22392801

  5. Brain antioxidant markers, cognitive performance and acetylcholinesterase activity of rats: efficiency of Sonchus asper

    Khan Rahmat

    2012-05-01

    Full Text Available Abstract Background Sonchus asper (SA is traditionally used as a folk medicine to treat mental disorders in Pakistan. The aim of this study was to investigate the effect of polyphenolic rich methanolic fraction of SA on cognitive performance, brain antioxidant activities and acetylcholinesterase activity in male rats. Methods 30 male Sprague–Dawley rats were equally divided into three groups in this study. Animals of group I (control received saline (vehicle, group II received SA (50 mg/kg body weight (b.w., and group III treated with SA (100 mg/kg b.w., orally in dimethyl sulphoxide (DMSO for 7 days. The effect of SA was checked on rat cognitive performance, brain antioxidatant and acetylcholinesterase activities. Evaluation of learning and memory was assessed by a step-through a passive avoidance test on day 6 after two habituation trials and an initial acquisition trial on day 5. Antioxidant potential was determined by measuring activities of superoxide dismutase (SOD, catalase (CAT, contents of thiobarbituric acid reactive substances (TBARS and reduced glutathione (GSH in whole-brain homogenates. Acetylcholinesterase (AChE activity was determined by the colorimetric method. Results Results showed that 100 mg/kg b.w., SA treated rats exhibited a significant improvement in learning and memory (step-through latency time. SA administration reduced lipid peroxidation products and elevated glutathione levels in the SA100-treated group. Furthermore, salt and detergent soluble AChE activity was significantly decreased in both SA-treated groups. Short-term orally supplementation of SA showed significant cognitive enhancement as well as elevated brain antioxidant enzymes and inhibited AChE activity. Conclusion These findings stress the critical impact of Sonchus asper bioactive components on brain function.

  6. Insecticidal properties of essential oils against Tribolium castaneum (Herbst) and their inhibitory effects on acetylcholinesterase and adenosine triphosphatases.

    Abou-Taleb, Hamdy K; Mohamed, Magdy I E; Shawir, Mohamed S; Abdelgaleil, Samir A M

    2016-01-01

    Essential oils from 20 Egyptian plants were obtained by using hydrodistillation. The chemical composition of the isolated oils was identified by gas chromatograph/mass spectrometer. Fumigant and contact toxicities of the essential oils were evaluated against the adults of Tribolium castaneum. In fumigation assays, the oil of Origanum vulgare (LC50 = 9.97 mg/L air) displayed the highest toxicity towards the adults of T. castaneum. In contact assays, the oils of Artemisia monosperma (LC50 = 0.07 mg/cm(2)) and O. vulgare (LC50 = 0.07 mg/cm(2)) were the most potent toxicants against the adults of T. castaneum. Biochemical studies showed that the tested oils caused pronounced inhibition of acetylcholinesterase (AChE) and adenosine triphosphatases (ATPases) isolated from the larvae of T. castaneum. The oil Cupressus macrocarpa (IC50 = 12.3 mg/L) was the most potent inhibitor of AChE, while the oil of Calistemon viminals (IC50 = 4.4 mg/L) was the most potent inhibitor of ATPases. PMID:25978134

  7. Acetylcholinesterase activity in marine gastropods as biomarker of neurotoxic contaminants

    Sarkar, A.; Gaitonde, D.C.S.; Vashistha, D.

    activity was expressed as the micro moles of acetic acid liberated per mg of proteins per minute and shown in term of arbitrary units. The AChE activity was compared with respect to that from a relatively uncontaminated region (Anjuna) along the Goa coast...

  8. Synthesis, characterization and cholinesterase enzymes inhibitory activity of 1-[3-methyl-5-(2,6,6-trimethyl-cyclohex-1-enyl)-4,5-dihydro-pyrazol-1-yl]-ethanone

    Mehdi, Sayed Hasan; Ghalib, Raza Murad; Hashim, Rokiah; da Silva, M. Fátima C. Guedes; Sulaiman, Othman; Murugaiyah, Vikneswaran; Marimuthu, Mani Maran; Naqvi, Mehnaz

    2013-10-01

    The crystal structure of the title compound, 1-[3-methyl-5-(2,6,6-trimethyl-cyclohex-1-enyl)-4,5-dihydro-pyrazol-1-yl]-ethanone has been determined by single crystal X-ray diffraction. It crystallizes in the orthorhombic space group P212121. The FTIR as well as the 1H and 13C NMR spectra of the compound were also recorded and briefly discussed. Compound 1 demonstrated good inhibitory activity against butyrylcholinesterase (BChE; IC50 = 46.42 μM) comparable to physostigmine. However it showed moderate inhibitory activity against acetylcholinesterase (AChE; IC50 = 157.31 μM). It showed moderate inhibitory activity against acetylcholinesterase and selective inhibitory activity towards butyrylcholinesterase enzyme.

  9. Effects of immature cashew nut-shell liquid (Anacardium occidentale) against oxidative damage in Saccharomyces cerevisiae and inhibition of acetylcholinesterase activity.

    De Lima, S G; Feitosa, C M; Citó, A M G L; Moita Neto, J M; Lopes, J A D; Leite, A S; Brito, M C; Dantas, S M M; Cavalcante, A A C Melo

    2008-01-01

    The cashew tree (Anacardium occidentale) represents one of the major cheapest sources of non-isoprenoid phenolic lipids, which have a variety of biological properties: they can act as molluscicides, insecticides, fungicides, have anti-termite properties, have medicinal applications, and demonstrate antioxidant activity in vitro. Immature cashew nut-shell liquid (iCNSL) is a unique natural source of unsaturated long-chain phenols. Their use has stimulated much research in order to prepare drug analogues for application in several fields. The objective of the present study was to determine whether iCNSL has antioxidant properties when used in strains of the yeast Saccharomyces cerevisiae and to measure the inhibitory activity of acetylcholinesterase. The constituents were identified using thin-layer chromatography, gas chromatography-mass spectrometry, Fourier transform infrared spectroscopy, and (1)H and (13)C nuclear magnetic resonance. The iCNSL contains anacardic acid, cardanol, cardol, and 2-methyl cardol. Immature cashew nut oil contains triacylglycerols, fatty acids, alkyl-substituted phenols, and cholesterol. The main constituents of the free fatty acids are palmitic (C(16:0)) and oleic acid (C(18:1)). iCNSL has excellent protective activities in strains of S. cerevisiae against oxidative damage induced by hydrogen peroxide and inhibits acetylcholinesterase activity. iCNSL may have an important role in protecting DNA against damage induced by reactive oxygen species, as well as hydrogen peroxide, generated by intra- and extracellular mechanisms. PMID:18949700

  10. The effect of dichlorvos on acetylcholinesterase activity in some tissues in rats

    Dere E.

    2010-01-01

    Full Text Available In this study, the changes with respect to time in the serum, brain, liver, kidney and small intestine acetylcholinesterase activities were investigated in both male and female rats administered dichlorvos intraperitoneally (i.p.. For this purpose, 4 mg kg-1 doses of dichlorvos were injected i.p. in the rats. The control groups, on the other hand, were administered physiological saline via the same route. Rats were killed by decapitation at 0, 2, 4, 8, 16, 32, 64 and 72 hours after administration of dichlorvos and tissues were harvested. Enzyme activities were determined following the necessary treatments. While a significant decrease in enzyme activities in the kidney and small intestine tissues with respect to time were not observed in either sex, a significant decrease in enzyme activities in the serum, as well as in the brain and liver tissues were observed. As a result of our study, acetylcholinesterase activity was found to be decreased compared to controls in both male and female rats from 2 and 4 hours. Enzyme inhibition continued for up to 72 hours.

  11. Dietary supplementation with fermented legumes modulate hyperglycemia and acetylcholinesterase activities in Streptozotocin-induced diabetes.

    Ademiluyi, Adedayo O; Oboh, Ganiyu; Boligon, Aline A; Athayde, Margareth L

    2015-12-01

    The study investigated the hypoglycemic and anticholinesterase activities of some fermented legumes (bambara groundnut and locust bean) in Streptozotocin (STZ)-induced diabetic rats. The rats were made diabetic by intraperitoneal administration of STZ (35mg/kg b.w.) and were fed diets containing fermented legumes (10% inclusion) for 14 days. The effect of the diets on blood glucose, pancreatic glutathione peroxidase (GPx) activity, reduced glutathione (GSH) and malondialdehyde (MDA) contents, α-amylase, intestinal α-glucosidase and acetylcholinesterase activities were studied. Significant (Pglucose, pancreatic MDA, α-amylase, intestinal α-glucosidase and acetylcholinesterase activities with concomitant decrease in pancreatic GPx and GSH contents were observed in diabetic rats. However, this trend was reversed in rats fed fermented legumes supplemented diets for 14 days. The HPLC-DAD finger printing revealed the presence of gallic acid, catechin, caffeic acid, epicatechin, rutin, isoquercitrin, quercitrin, quercetin and kaempferol as the dominant phenolic compounds of the fermented legumes. However, possible contributing role of some bioactive peptides could not be ruled out. Hence, the hypoglycemic and antiacetylcholinesterase activities of the fermented legume condiments could be attributed to their constituent phytochemicals. PMID:26349771

  12. Acetylcholinesterase-Inhibiting Activity of Pyrrole Derivatives from a Novel Marine Gliding Bacterium, Rapidithrix thailandica

    Khanit Suwanborirux; Anuchit Plubrukarn; Kornkanok Ingkaninan; Akkharawit Kanjana-opas; Supreeya Yuenyongsawad; Oraphan Sakulkeo; Yutthapong Sangnoi

    2008-01-01

    Acetylcholinesterase-inhibiting activity of marinoquinoline A (1), a new pyrroloquinoline from a novel species of a marine gliding bacterium Rapidithrix thailandica, was assessed (IC50 4.9 mM). Two related pyrrole derivatives, 3-(2'-aminophenyl)-pyrrole (3) and 2,2-dimethyl-pyrrolo-1,2-dihydroquinoline (4), were also isolated from two other strains of R. thailandica. The isolation of 3 froma natural source is reported here for the first time. Compound 4 was proposed to be an isolation artifac...

  13. The effect of dichlorvos on acetylcholinesterase activity in some tissues in rats

    Dere E.; Ari Ferda; Ugur S.

    2010-01-01

    In this study, the changes with respect to time in the serum, brain, liver, kidney and small intestine acetylcholinesterase activities were investigated in both male and female rats administered dichlorvos intraperitoneally (i.p.). For this purpose, 4 mg kg-1 doses of dichlorvos were injected i.p. in the rats. The control groups, on the other hand, were administered physiological saline via the same route. Rats were killed by decapitation at 0, 2, 4, 8, 16, 32, 64 and 72 hours after administr...

  14. Acetylcholinesterase-Inhibiting Activity of Pyrrole Derivatives from a Novel Marine Gliding Bacterium, Rapidithrix thailandica

    Sangnoi, Yutthapong; Sakulkeo, Oraphan; Yuenyongsawad, Supreeya; Kanjana-opas, Akkharawit; Ingkaninan, Kornkanok; Plubrukarn, Anuchit; Suwanborirux, Khanit

    2008-01-01

    Acetylcholinesterase-inhibiting activity of marinoquinoline A (1), a new pyrroloquinoline from a novel species of a marine gliding bacterium Rapidithrix thailandica, was assessed (IC50 4.9 μM). Two related pyrrole derivatives, 3-(2′-aminophenyl)-pyrrole (3) and 2,2-dimethyl-pyrrolo-1,2-dihydroquinoline (4), were also isolated from two other strains of R. thailandica. The isolation of 3 from a natural source is reported here for the first time. Compound 4 was proposed to be an isolation artifa...

  15. Sesquiterpenes produced by endophytic fungus Phomopsis cassiae with antifungal and acetylcholinesterase inhibition activities

    Two new diastereoisomeric cadinanes sesquiterpenes 3,9-dihydroxycalamenene (1-2), along with the known 3-hydroxycalamen-8-one (3) and aristelegone-A (4), were isolated from ethyl acetate extract of Phomopsis cassiae, an endophytic fungus in Cassia spectabilis. Their structures, including relative stereochemistry, were determined on the basis of detailed interpretation of 2D NMR spectra and comparison with related known compounds. Compounds 1-4 displayed antifungal activity against the phytopathogenic fungi Cladosporium cladosporioides and C. sphaerospermum, as well as inhibition of acetylcholinesterase. (author)

  16. Design, synthesis and preliminary structure-activity relationship investigation of nitrogen-containing chalcone derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors: a further study based on Flavokawain B Mannich base derivatives.

    Liu, Haoran; Fan, Haoqun; Gao, Xiaohui; Huang, Xueqing; Liu, Xianjun; Liu, Linbo; Zhou, Chao; Tang, Jingjing; Wang, Qiuan; Liu, Wukun

    2016-08-01

    In order to study the structure-activity relationship of Flavokawain B Mannich-based derivatives as acetylcholinesterase (AChE) inhibitors in our recent investigation, 20 new nitrogen-containing chalcone derivatives (4 a-8d) were designed, synthesized, and evaluated for AChE inhibitory activity in vitro. The results suggested that amino alkyl side chain of chalcone dramatically influenced the inhibitory activity against AChE. Among them, compound 6c revealed the strongest AChE inhibitory activity (IC50 value: 0.85 μmol/L) and the highest selectivity against AChE over BuChE (ratio: 35.79). Enzyme kinetic study showed that the inhibition mechanism of compound 6c against AChE was a mixed-type inhibition. The molecular docking assay showed that this compound can both bind with the catalytic site and the peripheral site of AChE. PMID:26186269

  17. The inhibition activity of selected beta-carboline alkaloids on enzymes of acetylcholinesterase and butyrylcholinesterase.

    Krsková, Zuzana; Martin, Jan; Dusek, Jaroslav

    2011-06-01

    This thesis deals with testing of inhibition activity beta-carboline alkaloids on activity of enzymes acetylcholinesterase (ACHE) and butyrylcholinesterase (BUCHE) using test "Fast Blue B salt" at TLC desk and Ellman's test using spectrophotometer. It was also investigated how dimethylsulfoxide used as a solvent in combination with water affects activity of enzymes and alkaloids. Results show harmine in form of base and salt in water and in mixture of DMSO and water has the hightest inhibition activity on ACHE using eserine as reference substance. Harmalol in form of salt in water and harmine in form of base and salt in mixture of DMSO and water has the hightest activity on BUCHE. It was find out that DMSO considerably affects activity of enzymes and alkaloids. PMID:21838142

  18. Post-irradiation changes in acetylcholinesterase and butyrylcholinesterase activity in blood platelets of whole-body irradiated rats

    After 24, 96 and 144 hours following whole-body irradiation of rats with 8 Gy an increased acetylcholinesterase activity was found in platelets. The activity of butyrylcholinesterase in platelets increased in all investigated intervals after whole-body irradiation of rats with 8 Gy. The highest values were recorded after 144, 192 and 264 hours. (author)

  19. Effects of endosulfan on brain acetylcholinesterase activity in juvenile bluegill sunfish

    The effects of endosulfan upon brain acetylcholinesterase (AChE) activity were measured in juvenile blue gill sunfish (Lepomis macrochirus). Based on exposure durations of 0, 24, 48, 72, and 96 h and 1 week at 1.0 μg/L (just below the LC50 of 1.2 μg/L for this species), step-wise decreases in AChE activity were noted, corresponding to 0%, 3.57%, 12.65%, 14.23%, 16.31%, and 3.11% inhibition, respectively. Total brain protein concentrations were measured to test the accuracy of the Ache data with no significant anomalies. The duration of exposure was related to the reduction in the AChE activities which reflected the biotoxicity of endosulfan. The changes in the AChE activities will certainly affect the normal behavior of the juvenile blue gill which is detrimental to their very existence in the natural habitat

  20. Water Extractable Phytochemicals from Peppers (Capsicum spp. Inhibit Acetylcholinesterase and Butyrylcholinesterase Activities and Prooxidants Induced Lipid Peroxidation in Rat Brain In Vitro

    Omodesola O. Ogunruku

    2014-01-01

    Full Text Available Background. This study sought to investigate antioxidant capacity of aqueous extracts of two pepper varieties (Capsicum annuum var. accuminatum (SM and Capsicum chinense (RO and their inhibitory effect on acetylcholinesterase and butyrylcholinesterase activities. Methods. The antioxidant capacity of the peppers was evaluated by the 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid (ABTS radical scavenging ability and ferric reducing antioxidant property. The inhibition of prooxidant induced lipid peroxidation and cholinesterase activities in rat brain homogenates was also evaluated. Results. There was no significant difference (P>0.05 in the total phenol contents of the unripe and ripe Capsicum spp. extracts. Ripe and unripe SM samples had significantly higher (P<0.05 ABTS* scavenging ability than RO samples, while the ripe fruits had significantly higher (P<0.05 ferric reducing properties in the varieties. Furthermore, the extracts inhibited Fe2+ and quinolinic acid induced lipid peroxidation in rats brain homogenates in a dose-dependent manner. Ripe and unripe samples from SM had significantly higher AChE inhibitory abilities than RO samples, while there was no significant difference in the BuChE inhibitory abilities of the pepper samples. Conclusion. The antioxidant and anticholinesterase properties of Capsicum spp. may be a possible dietary means by which oxidative stress and symptomatic cognitive decline associated with neurodegenerative conditions could be alleviated.

  1. Lipoxygenase inhibitory activity of anacardic acids.

    Ha, Tae Joung; Kubo, Isao

    2005-06-01

    6[8'(Z)-pentadecenyl]salicylic acid, otherwise known as anacardic acid (C15:1), inhibited the linoleic acid peroxidation catalyzed by soybean lipoxygenase-1 (EC 1.13.11.12, type 1) with an IC50 of 6.8 microM. The inhibition of the enzyme by anacardic acid (C15:1) is a slow and reversible reaction without residual activity. The inhibition kinetics analyzed by Dixon plots indicates that anacardic acid (C15:1) is a competitive inhibitor and the inhibition constant, KI, was obtained as 2.8 microM. Although anacardic acid (C15:1) inhibited the linoleic acid peroxidation without being oxidized, 6[8'(Z),11'(Z)-pentadecadienyl]salicylic acid, otherwise known as anacardic acid (C15:2), was dioxygenated at low concentrations as a substrate. In addition, anacardic acid (C15:2) was also found to exhibit time-dependent inhibition of lipoxygenase-1. The alk(en)yl side chain of anacardic acids is essential to elicit the inhibitory activity. However, the hydrophobic interaction alone is not enough because cardanol (C15:1), which possesses the same side chain as anacardic acid (C15:1), acted neither as a substrate nor as an inhibitor. PMID:15913294

  2. Effects of hunger level and nutrient balance on survival and acetylcholinesterase activity of dimethoate exposed wolf spiders

    Pedersen, Lars-Flemming; Dall, Lars G.; Sorensen, Bo C.; Mayntz, David; Toft, Soren

    2002-01-01

    were created by feeding them fruit flies of either high or low nutrient content for 28 days. Both groups were then split into satiated and 14 days starved subgroups. Each of these was further divided into insecticide treated and control halves. Survivorship and acetylcholinesterase (AChE) activity...

  3. Use of cytectrene marked by the technetium 99 to study the activity of Acetylcholinesterase in the rat brain

    Alzheimer's disease is a degenerative neurological disorder that causes progressive and irreversible loss of mental functions. It is the most common form of dementia and is characterized by a decrease in serotonergic neurons that carry the 5HT1A receptors. Derivatives piperidine with a tertiary amine and ester are similar to acetylcholine [natural substrate of acetylcholinesterase)], we used the cytectrene [molecule based piperidine marked the technetium 99m] as a substrate to investigate the activity of Acetylcholinesterase in the brain. The use of cytectrene for the quantitative measurement of the activity of the Acetylcholinesterase in the brain depends on the rate of hydrolysis and the enzymatic specificity. The results showed that the cytectrene can be used as a substrate for a precise and quantitative determination of the activity of this enzyme. The use of cytectrene as a substrate of Acetylcholinesterase and determination of its activity can use this molecule as an agent for early diagnosis of Alzheimer's disease. The results will, therefore, not only their importance on a fundamental level but also on a plan applied in the medical field. (Author)

  4. Effects of Green Tea Extract on Learning, Memory, Behavior and Acetylcholinesterase Activity in Young and Old Male Rats

    Kaur, Tranum; Pathak, C. M.; Pandhi, P.; Khanduja, K. L.

    2008-01-01

    Objective: To study the effects of green tea extract administration on age-related cognition in young and old male Wistar rats. Methods: Young and old rats were orally administered 0.5% green tea extract for a period of eight weeks and were evaluated by passive avoidance, elevated maze plus paradigm and changes in acetylcholinesterase activity.…

  5. Monoamine oxidase inhibitory activities of heterocyclic chalcones.

    Minders, Corné; Petzer, Jacobus P; Petzer, Anél; Lourens, Anna C U

    2015-11-15

    Studies have shown that natural and synthetic chalcones (1,3-diphenyl-2-propen-1-ones) possess monoamine oxidase (MAO) inhibition activities. Of particular importance to the present study is a report that a series of furanochalcones acts as MAO-B selective inhibitors. Since the effect of heterocyclic substitution, other than furan (and more recently thiophene, piperidine and quinoline) on the MAO inhibitory properties of the chalcone scaffold remains unexplored, the aim of this study was to synthesise and evaluate further heterocyclic chalcone analogues as inhibitors of the human MAOs. For this purpose, heterocyclic chalcone analogues that incorporate pyrrole, 5-methylthiophene, 5-chlorothiophene and 6-methoxypyridine substitution were examined. Seven of the nine synthesised compounds exhibited IC50 values heterocyclic chalcones are reversible and competitive MAO inhibitors. 4h, however, may exhibit tight-binding to MAO-B, a property linked to its thiophene moiety. We conclude that high potency chalcones such as 4h represent suitable leads for the development of MAO-B inhibitors for the treatment of Parkinson's disease and possibly other neurodegenerative disorders. PMID:26432037

  6. Conformation-activity studies on the interaction of berberine with acetylcholinesterase:Physical chemistry approach

    Jin Xiang; Changping Yu; Fang Yang; Ling Yang; Hong Ding

    2009-01-01

    Berberine has been reported as an acetylcholinesterase (AChE) inhibitor.With significantly low cytotoxicity,berberine will be developed for the clinical treatment of Alzheimer disease (AD) with higher efficacy and fewer side effects.This work investigated the structure change events of AChE that occur during the interaction with berberine by isothermal titration calorimetry (ITC),fluorescence titration,and circular dichroism (CD).The results show that the binding of berberine to AChE is mainly driven by a favorable entropy increase with a less weak affinity.Berberine causes a loss in enzymatic activity at a concentration much below the concentration which gradually exposed the tryptophan residues to a more hydrophilic environment and unfolded the protein,which indicates that the inhibition of AChE with berberine includes the main contributions of interaction and minor conformation change of the protein induced by the alkaloid.

  7. Intraclonal variability in Daphnia acetylcholinesterase activity: the implications for its applicability as a biomarker.

    Printes, Liane Biehl; Callaghan, Amanda

    2003-09-01

    The relationship between individual growth and acetylcholinesterase (AChE) activity was evaluated for Daphnia magna. Analysis on the influence of two different culture media on baseline AChE activity was performed with Daphnia similis. The results indicated an inverse relationship between D. magna body length and AChE activity. An increase in total protein, which was not proportional to an increase in the rate of the substrate hydrolysis (delta absorbance/min), seems to be the reason for this inverse size versus AChE activity relationship. Therefore, toxicants such as phenobarbital, which affect protein and size but not AChE activity directly, have an overall affect on AChE activity. In contrast, the AChE inhibitor parathion altered AChE activity but not protein. Culture medium also had a significant affect on AChE activity in D. similis. Changes in total protein seem to be the main reason for the variations in baseline AChE activity in Daphnia observed in the different evaluations performed in this work. Therefore, AChE activity in Daphnia must be interpreted carefully, and variations related to changes in total protein must be taken into account when applying this enzyme as a biomarker in biological monitoring. PMID:12959529

  8. Acetylcholinesterase activities in marine snail (Cronia contracta) as a biomarker of neurotoxic contaminants along the Goa coast, West coast of India

    Gaitonde, D.; Sarkar, A.; Kaisary, S.; DeSilva, C.; Dias, C.F.M.; Rao, P.V.S.S.D.P.; Ray, D.; Nagarajan, R.; DeSousa, S.N.; Sarkar, S.; Patill, D.

    The measurement of acetylcholinesterase (AChE) activity is used worldwide as a biomarker of environmental contamination due to neurotoxic substances. In the present study the AChE activities was measured in marine snails (Cronia contracta) collected...

  9. Geranylphenazinediol, an Acetylcholinesterase Inhibitor Produced by aStreptomycesSpecies

    Ohlendorf, Birgit; Schulz, Dirk; Erhard, Arlette; Nagel, Kerstin; Imhoff, Johannes F.

    2012-01-01

    Geranylphenazinediol (1), a new phenazine natural product, was produced by the Streptomyces sp. strain LB173, which was isolated from a marine sediment sample. The structure was established by analysis of NMR and MS data. 1 inhibited the enzyme acetylcholinesterase in the low micromolar range and showed weak antibacterial activity. In order to get a more detailed picture of the activity profile of 1, its inhibitory potential was compared to that of related structures

  10. Geranylphenazinediol, an acetylcholinesterase inhibitor produced by a Streptomyces species.

    Ohlendorf, Birgit; Schulz, Dirk; Erhard, Arlette; Nagel, Kerstin; Imhoff, Johannes F

    2012-07-27

    Geranylphenazinediol (1), a new phenazine natural product, was produced by the Streptomyces sp. strain LB173, which was isolated from a marine sediment sample. The structure was established by analysis of NMR and MS data. 1 inhibited the enzyme acetylcholinesterase in the low micromolar range and showed weak antibacterial activity. In order to get a more detailed picture of the activity profile of 1, its inhibitory potential was compared to that of related structures. PMID:22775474

  11. In vitro inhibition of acetylcholinesterase by crude plant extracts from Colombian flora.

    Niño, Jaime; Hernández, Jimmy A; Correa, Yaned M; Mosquera, Oscar M

    2006-11-01

    The methanol extracts from five different plant families (Asteraceae, Euphorbiaceae, Melastomataceae, Rubiaceae, and Solanaceae) collected at Regional Natural Park Ucumarí (Colombia), were screened for their acetylcholinesterase inhibitory activity through the modified Ellman's spectrophotometric method. The best inhibitory activities on this study were shown by the extracts of Solanum leucocarpum Dunal (IC50 = 204.59 mg/l) and Witheringia coccoloboides (Damm) (IC50 = 220.68 mg/l), both plants belonging to the Solanaceae family. PMID:17160288

  12. Nature of stress: differential effects on brain acetylcholinesterase activity and memory in rats.

    Das, Amitava; Rai, Deepak; Dikshit, Madhu; Palit, Gautam; Nath, Chandishwar

    2005-09-16

    Effect of acute, chronic-predictable and chronic-unpredictable stress on memory and acetylcholinesterase (AChE) was investigated in rats. The animals were subjected to 3 type of stressors--(1) acute immobilization stress, (2) chronic-predictable stress i.e., immobilization daily for 5 consecutive days and (3) chronic-unpredictable stress that included reversal of light/dark cycle, over-night fasting, forced-swimming, immobilization and forced exercise in random unpredictable manner daily for 5 consecutive days. Learning and memory function was studied by single trial Passive avoidance test. AChE activity was assayed spectrophotometrically in the detergent (DS) and salt (SS) soluble fractions in different brain regions. Learning was obtained in acute and chronic-predictable stress groups but not in chronic-unpredictable group. Acute, chronic-predictable and chronic-unpredictable stress caused significant decrease in AChE activity in the DS fraction of cortex, hippocampus and hypothalamus as compared to control. Results indicate that AChE in DS fraction is predominantly affected in stressed and stressed-trained group but cognition is affected only by chronic-unpredictable stress. In acute and chronic-predictable groups the decreased AChE activity in the hippocampal DS fraction during learning may be responsible to maintain cognitive function by enhancing the cholinergic activity. PMID:16098992

  13. The effects of a food product containing lactic acid on the activity of acetylcholinesterase

    Andre-Michael Beer; Julian Lukanov; Yordanka Uzunova; Plamen Sagortchev

    2012-01-01

    Objective: Patients reported that a food product containing lactic acid improved their memory and thought processes. The ingredients of the tested food product are compound substances and smooth muscle fibre, the appropriate medium in which to analyse their effects. Acetylcholinesterase inhibitors are used to treat memory loss and failing thought performance. The aim of this study was to compare the effects of the lactic acid food product with the effects of acetylcholinesterase inhibitors. M...

  14. Alkaloids from Peumus boldus and their acetylcholinesterase, butyrylcholinesterase and prolyl oligopeptidase inhibition activity.

    Hošt'álková, Anna; Opletal, Lubomír; Kuneš, Jiří; Novák, Zdeněk; Hrabinová, Martina; Chlebek, Jakub; Čegan, Lukáš; Cahlíková, Lucie

    2015-04-01

    Eleven isoquinoline alkaloids (1-11) were isolated from dried leaves of Peumus boldus Mol. by standard chromatographic methods. The chemical structures were elucidated by MS, and 1D and 2D NMR spectroscopic analysis, and by comparison with literature data. Compounds isolated in sufficient amount were evaluated for their acetylcholinesterase, and butyrylcholinesterase inhibition activity using Ellman's method. In the prolyl oligopeptidase assay, Z-Gly-Pro-p-nitroanilide was used as substrate. Promising butyrylcholinesterase inhibition activities were demonstrated by two benzylisoquinoline alkaloids, reticuline (8) and N-methylcoclaurine (9), with IC50 values of 33.6 ± 3.0 µM and 15.0 ± 1.4 µM, respectively. Important prolyl oligopeptidase inhibition activities were shown by N-methyllaurotetanine (6) and sinoacutine (4) with IC50 values of 135.4 ± 23.2 µM and 143.1 ± 25.4 µM, respectively. Other tested compounds were considered inactive. PMID:25973480

  15. Simplified methods for in vivo measurement of acetylcholinesterase activity in rodent brain

    Simplified methods for in vivo studies of acetylcholinesterase (AChE) activity in rodent brain were evaluated using N-[11C]methylpiperidinyl propionate ([11C]PMP) as an enzyme substrate. Regional mouse brain distributions were determined at 1 min (representing initial brain uptake) and 30 min (representing trapped product) after intravenous [11C]PMP administration. Single time point tissue concentrations (percent injected dose/gram at 30 min), tissue concentration ratios (striatum/cerebellum and striatum/cortex ratios at 30 min), and regional tissue retention fractions (defined as percent injected dose 30 min/percent injected dose 1 min) were evaluated as measures of AChE enzymatic activity in mouse brain. Studies were carried out in control animals and after dosing with phenserine, a selective centrally active AChE inhibitor; neostigmine, a peripheral cholinesterase inhibitor; and a combination of the two drugs. In control and phenserine-treated animals, absolute tissue concentrations and regional retention fractions provide good measures of dose-dependent inhibition of brain AChE; tissue concentration ratios, however, provide erroneous conclusions. Peripheral inhibition of cholinesterases, which changes the blood pharmacokinetics of the radiotracer, diminishes the sensitivity of all measures to detect changes in central inhibition of the enzyme. We conclude that certain simple measures of AChE hydrolysis rates for [11C]PMP are suitable for studies where alterations of the peripheral blood metabolism of the tracer are kept to a minimum

  16. Inhibition of acetylcholinesterase and cytochrome oxidase activity in Fasciola gigantica cercaria by phytoconstituents.

    Sunita, Kumari; Habib, Maria; Kumar, P; Singh, Vinay Kumar; Husain, Syed Akhtar; Singh, D K

    2016-02-01

    Fasciolosis is an important cattle and human disease caused by Fasciola hepatica and Fasciola gigantica. One of the possible methods to control this problem is to interrupt the life cycle of Fasciola by killing its larva (redia and cercaria) in host snail. Molecular identification of cercaria larva of F. gigantica was done by comparing the nucleotide sequencing with adult F. gigantica. It was noted that nucleotide sequencing of cercaria larva and adult F. gigantica were 99% same. Every month during the year 2011-2012, in vivo treatment with 60% of 4 h LC50 of phyto cercaricides citral, ferulic acid, umbelliferone, azadirachtin and allicin caused significant inhibition of acetylcholinesterase (AChE) and cytochrome oxidase activity in the treated cercaria larva of F. gigantica. Whereas, activity of both enzymes were not significantly altered in the nervous tissues of vector snail Lymnaea acuminata exposed to same treatments. Maximum reduction in AChE (1.35% of control in month of June) and cytochrome oxidase (3.71% of control in the month of July) activity were noted in the cercaria exposed to 60% of 4 h LC50 of azadirachtin and allicin, respectively. PMID:26536397

  17. Calcium-activated butyrylcholinesterase in human skin protects acetylcholinesterase against suicide inhibition by neurotoxic organophosphates

    The human epidermis holds an autocrine acetylcholine production and degradation including functioning membrane integrated and cytosolic butyrylcholinesterase (BuchE). Here we show that BuchE activities increase 9-fold in the presence of calcium (0.5 x 10-3M) via a specific EF-hand calcium binding site, whereas acetylcholinesterase (AchE) is not affected. 45Calcium labelling and computer simulation confirmed the presence of one EF-hand binding site per subunit which is disrupted by H2O2-mediated oxidation. Moreover, we confirmed the faster hydrolysis by calcium-activated BuchE using the neurotoxic organophosphate O-ethyl-O-(4-nitrophenyl)-phenylphosphonothioate (EPN). Considering the large size of the human skin with 1.8 m2 surface area with its calcium gradient in the 10-3M range, our results implicate calcium-activated BuchE as a major protective mechanism against suicide inhibition of AchE by organophosphates in this non-neuronal tissue

  18. Assessment of Acetylcholinesterase Activity Using Indoxylacetate and Comparison with the Standard Ellman’s Method

    Kamil Kuca

    2011-04-01

    Full Text Available Assay of acetylcholinesterase (AChE activity plays an important role in diagnostic, detection of pesticides and nerve agents, in vitro characterization of toxins and drugs including potential treatments for Alzheimer’s disease. These experiments were done in order to determine whether indoxylacetate could be an adequate chromogenic reactant for AChE assay evaluation. Moreover, the results were compared to the standard Ellman’s method. We calculated Michaelis constant Km (2.06 × 10−4 mol/L for acetylthiocholine and 3.21 × 10−3 mol/L for indoxylacetate maximum reaction velocity Vmax (4.97 × 10−7 kat for acetylcholine and 7.71 × 10−8 kat for indoxylacetate for electric eel AChE. In a second part, inhibition values were plotted for paraoxon, and reactivation efficacy was measured for some standard oxime reactivators: obidoxime, pralidoxime (2-PAM and HI-6. Though indoxylacetate is split with lower turnover rate, this compound appears as a very attractive reactant since it does not show any chemical reactivity with oxime antidots and thiol used for the Ellman’s method. Thus it can be advantageously used for accurate measurement of AChE activity. Suitability of assay for butyrylcholinesterase activity assessment is also discussed.

  19. Effects of Androctonus crassicauda (Olivier, 1807) (scorpiones: buthidae) venom on rats: correlation among acetylcholinesterase activities and electrolytes levels

    O Ozkan; S. Adiguzel; Kar, S.; Kurt, M.; S. Yakistiran; Y Cesaretli; Orman, M; KARAER, Z.

    2007-01-01

    Scorpions can be considered living fossils because they have changed so little during the last 400 million years. They are venomous arthropods of the Arachnida class and regarded as relatives of spiders, ticks and mites. The aim of the present study was to evaluate the toxicity of Androctonus crassicauda (Olivier, 1807) venom and its effects on the acetylcholinesterase (AchE) activity and on electrolytes levels in rats. Animals were divided into seven groups of five rats each. Test groups rec...

  20. Toxicity of azodrin on the morphology and acetylcholinesterase activity of the earthworm Eisenia foetida

    The acute toxicity of azodrin (monocrotophos, an organophosphorus insecticide) was determined on a soil organism, Eisenia foetida. The median lethal concentrations (LC50) were derived from a 48-h paper contact test and from artificial soil tests. The LC50 of azodrin in the paper contact test was 0.46±0.1 μg cm-2 (23±6 mg L-1) and those in the 7- and 14-day artificial soil tests were 171±21 and 132±20 mg kg-1, respectively. The neurotoxic potentiality of azodrin was assessed by using a marker enzyme, acetylcholinesterase (AChE; EC 3.1.1.7) in both in vitro and in vivo experiments. The progressive signs of morphological destruction are correlated with percentage inhibition of AChE in the in vivo experiments. The kinetics of AChE activity in the presence and absence of azodrin indicated that the toxicant is competitive in nature. This study demonstrated that azodrin causes concentration-dependent changes in the morphology and AChE activity of the earthworm E. foetida

  1. Maternal caffeine exposure alters neuromotor development and hippocampus acetylcholinesterase activity in rat offspring.

    Souza, Ana Claudia; Souza, Andressa; Medeiros, Liciane Fernandes; De Oliveira, Carla; Scarabelot, Vanessa Leal; Da Silva, Rosane Souza; Bogo, Mauricio Reis; Capiotti, Katiucia Marques; Kist, Luiza Wilges; Bonan, Carla D; Caumo, Wolnei; Torres, Iraci L S

    2015-01-21

    The objective of this study was to evaluate the effects of maternal caffeine intake on the neuromotor development of rat offspring and on acetylcholine degradation and acetylcholinesterase (AChE) expression in the hippocampus of 14-day-old infant rats. Rat dams were treated with caffeine (0.3g/L) throughout gestation and lactation until the pups were 14 days old. The pups were divided into three groups: (1) control, (2) caffeine, and (3) washout caffeine. The washout group received a caffeine solution until the seventh postnatal day (P7). Righting reflex (RR) and negative geotaxis (NG) were assessed to evaluate postural parameters as an index of neuromotor reflexes. An open-field (OF) test was conducted to assess locomotor and exploratory activities as well as anxiety-like behaviors. Caffeine treatment increased both RR and NG latency times. In the OF test, the caffeine group had fewer outer crossings and reduced locomotion compared to control, while the washout group showed increased inner crossings in relation to the other groups and fewer rearings only in comparison to the control group. We found decreased AChE activity in the caffeine group compared to the other groups, with no alteration in AChE transcriptional regulation. Chronic maternal exposure to caffeine promotes important alterations in neuromotor development. These results highlight the ability of maternal caffeine intake to interfere with cholinergic neurotransmission during brain development. PMID:25451122

  2. A recombinant wheat serpin with inhibitory activity

    Rasmussen, Søren K; Dahl, Søren Weis; Nørgård, Anette;

    1996-01-01

    A full-length clone encoding the wheat (Triticum aestivum L.) serpin WSZ1 was isolated from a cDNA library based on mRNA from immature grain. The 398 amino acid sequence deduced from the cDNA was corroborated by sequencing CNBr peptides of WSZ1 purified from resting grain. WSZ1 belongs to the...... sequencing indicated that only few serpins are encoded by wheat, but at least three distinct genes are expressed in the grain. Cleavage experiments on a chymotrypsin column suggested a Gln-Gln reactive site bond not previously observed in inhibitory serpins....

  3. Human cerebral acetylcholinesterase activity measured with positron emission tomography: procedure, normal values and effect of age

    The regional cerebral metabolic rate of [11C]N-methyl-4-piperidyl acetate, which is nearly proportional to regional cerebral acetylcholinesterase (AChE) activity, was measured by dynamic positron emission tomography in 20 healthy subjects with a wide age range (24-89 years). Quantitative measurement was achieved using a kinetic model which consisted of arterial plasma and cerebral tissue compartments. The plasma input function was obtained using thin-layer chromatography and an imaging phosphor plate system at frequent sampling intervals to catch the rapid metabolism of the tracer in the blood. The distribution of the rate constant k3, an index of AChE activity, agreed well with reported post-mortem AChE distribution in the cerebral cortex (0.067-0.097 min-1) and thalamus (0.268 min-1), where AChE activity was low to moderate. The k3 values in the striatum and cerebellum, where AChE activity was very high, did not respond linearly to AChE activity because of increased flow dependency. No significant effect of age was found on AChE activity of the cerebral cortex, suggesting that the ascending central cholinergic system is preserved in normal aging. This study has shown that quantitative measurement of enzyme activity in the living brain is possible through appropriate modelling of tracer kinetics and accurate measurement of the input function. The method should be applicable to patients with Alzheimer's disease and those with other kinds of dementia whose central cholinergic system has been reported to be disturbed. (orig.)

  4. Human cerebral acetylcholinesterase activity measured with positron emission tomography: procedure, normal values and effect of age

    Namba, Hiroki [Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba (Japan)]|[Division of Neurological Surgery, Chiba Cancer Center, Chiba (Japan); Iyo, Masaomi [Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba (Japan)]|[Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu (Japan); Fukushi, Kiyoshi; Suhara, Tetsuya; Sudo, Yasuhiko; Suzuki, Kazutoshi; Irie, Toshiaki [Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba (Japan); Shinotoh, Hitoshi [Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba (Japan)]|[Department of Neurology, Chiba University School of Medicine, Chiba (Japan); Nagatsuka, Shin-ichiro [Advanced Technology for Medical Imaging, National Institute of Radiological Sciences, Chiba (Japan)]|[Tokai Research Laboratories, Daiichi Pure Chemical Co., Ltd., Ibaraki (Japan)

    1999-02-01

    The regional cerebral metabolic rate of [{sup 11}C]N-methyl-4-piperidyl acetate, which is nearly proportional to regional cerebral acetylcholinesterase (AChE) activity, was measured by dynamic positron emission tomography in 20 healthy subjects with a wide age range (24-89 years). Quantitative measurement was achieved using a kinetic model which consisted of arterial plasma and cerebral tissue compartments. The plasma input function was obtained using thin-layer chromatography and an imaging phosphor plate system at frequent sampling intervals to catch the rapid metabolism of the tracer in the blood. The distribution of the rate constant k{sub 3}, an index of AChE activity, agreed well with reported post-mortem AChE distribution in the cerebral cortex (0.067-0.097 min{sup -1}) and thalamus (0.268 min{sup -1}), where AChE activity was low to moderate. The k{sub 3} values in the striatum and cerebellum, where AChE activity was very high, did not respond linearly to AChE activity because of increased flow dependency. No significant effect of age was found on AChE activity of the cerebral cortex, suggesting that the ascending central cholinergic system is preserved in normal aging. This study has shown that quantitative measurement of enzyme activity in the living brain is possible through appropriate modelling of tracer kinetics and accurate measurement of the input function. The method should be applicable to patients with Alzheimer`s disease and those with other kinds of dementia whose central cholinergic system has been reported to be disturbed. (orig.) With 8 figs., 1 tab., 21 refs.

  5. Fatty Acid Composition, Antioxidant, Anticholinesterase and Tyrosinase Inhibitory Activities of Four Serratula Species from Anatolia

    Gülsen Tel

    2013-03-01

    Full Text Available Serratula L. (Astareceae rich in ecdysteroid, phytoecdysteroids and flavonoids some have various biological activities including antibacterial and antitumor. The fatty acid profiles of four Serratula species were investigated by using GC and GC–MS techniques. Palmitic, oleic, linoleic and linolenic acids were found to be the main fatty acids. The unsaturation percentage was between 27.24-50.47%. The antioxidant activity of the extracts was determined by using four complementary tests; namely, β-carotene-linoleic acid, DPPH• scavenging, CUPRAC and ferrous-ions chelating assays. The methanol extract of S. lasiocephala showed the highest activity in β-carotene-linoleic acid, DPPH• scavenging and CUPRAC assays, while the hexane extract of S. radiata exhibited the best metal chelating activity. In addition, total phenolic and total flavonoid contents in the extracts were determined as pyrocatechol and quercetin equivalents, respectively. The in vitro anticholinesterase activity of extracts were tested against acetylcholinesterase (AChE and butyrylcholinesterase (BChE which are the key enzymes taking place in pathogenesis of Alzheimer’s disease. Besides, the extracts were tested in vitro against tyrosinase enzyme which is associated with melanin hyperpigmentation. Except the hexane extracts of S. radiata and S. lasiocephala, the extracts showed moderate inhibition against AChE and BChE, while the only hexane extract of S. erucifolia and methanol extract of S. radiata exhibited tyrosinase inhibitory activity.

  6. Formulation and characterization of novel functional beverages with antioxidant and anti-acetylcholinesterase activities

    Suree Nanasombat

    2015-01-01

    beverages B1, B2, B3, B4 and B5 in the ratio of 60:40 to prepare alcoholic beverages W1, W2, W3, W4 and W5, respectively. Two different fermentation conditions (fermentation with or without pieces of sliced medicinal plant residue, PMPR were compared. After fermenting, racking and aging, all alcoholic beverages, as well as all non-alcoholic beverages,were analyzed for some phytochemical properties. Results: Grape fermented with PMPR had higher anti-acetylcholinesterase and antioxidant activities, and total phenolics, flavonoids and tannins, compared to the others. Among all nonalcoholic beverages, the beverage B3 contained the highest anti-acetylcholinesterase (22.78% inhibition at 1:10,000 dilution and antioxidant activities (reducing capacity, 4.22 mmol Fe(II/100 mL, total phenolics, flavonoids, and tannins (494.44 mg gallic acid equivalents (GAE, 383.22 mg catechin equivalents (CE and 338.29 mg tannic acid equivalents ((TAE/100 mL, respectively. Among all alcoholic beverages, the beverage W3 (fermented with PMPR exhibited the highest antioxidant activity (DPPH radical inhibition, 95.99 mg trolox equivalents and reducing capacity, 3.57 mmol Fe(II /100 mL, total phenolics, flavonoids and tannins (239.71 mg GAE, 372.67 mg CE and 157.67 mg TAE/100 mL, respectively. The beverage W2 (fermented with PMPR had the highest anti-acetylcholinesterase activity (21.35% inhibition at 1:10,000 dilution. Conclusion: The beverages B3, W2 and W3 contained valuable sources of natural antioxidants and acetylcholinesterase inhibitors, and may provide health benefits when consumed.

  7. Enzyme Inhibitory Properties, Antioxidant Activities, and Phytochemical Profile of Three Medicinal Plants from Turkey

    Gokhan Zengin

    2015-01-01

    Full Text Available We aimed to investigate the inhibitory potential of three medicinal plants (Hedysarum varium, Onobrychis hypargyrea, and Vicia truncatula from Turkey against key enzymes involved in human pathologies, namely, diabetes (α-amylase and α-glucosidase, neurodegenerative disorders (tyrosinase, acetylcholinesterase, and butyrylcholinesterase, and hyperpigmentation (tyrosinase. The antioxidant potential, phenolic and flavonoid content of ethyl acetate, and methanolic and aqueous extracts were investigated using in vitro assays. The total antioxidant capacity (TAC, β-carotene/linoleic acid bleaching activity, 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH•, 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS•+, cupric ion reducing antioxidant capacity (CUPRAC, ferric reducing antioxidant power (FRAP, and metal chelating activity on ferrous ions were used to evaluate the antioxidant capabilities of the extracts. The half-maximal inhibitory concentrations (IC50 of the extracts on cholinesterase, tyrosinase, and α-amylase were significantly higher than the references, galantamine, kojic acid, and acarbose, respectively. The half-maximal effective concentrations (EC50 of the extracts on TAC, CUPRAC, and FRAP were significantly higher than trolox. The phenol and flavonoid contents of the plant extracts were in the range 20.90±0.190–83.25±0.914 mg gallic acid equivalent/g extract and 1.45±0.200–39.71±0.092 mg rutin equivalent/g extract, respectively. The plants were found to possess moderate antioxidant capacities and interesting inhibitory action against key enzymes.

  8. Detection of Carbofuran with Immobilized Acetylcholinesterase Based on Carbon Nanotubes-Chitosan Modified Electrode

    Shuping Zhang; Shaoyang Li; Jie Ma; Fei Xiong; Song Qu

    2013-01-01

    A sensitive and stable enzyme biosensor based on efficient immobilization of acetylcholinesterase (AChE) to MWNTs-modified glassy carbon electrode (GCE) with chitosan (CS) by layer-by-layer (LBL) technique for rapid determination of carbofuran has been devised. According to the inhibitory effect of carbamate pesticide on the enzymatic activity of AChE, we use carbofuran as a model pesticide. The inhibitory effect of carbofuran on the biosensor was proportional to concentration of carbofuran i...

  9. Cinnamomum loureirii Extract Inhibits Acetylcholinesterase Activity and Ameliorates Trimethyltin-Induced Cognitive Dysfunction in Mice.

    Kim, Cho Rong; Choi, Soo Jung; Kwon, Yoon Kyung; Kim, Jae Kyeom; Kim, Youn-Jung; Park, Gwi Gun; Shin, Dong-Hoon

    2016-01-01

    The pathogenesis of Alzheimer's disease (AD) has been linked to the deficiency of neurotransmitter acetylcholine (ACh) in the brain, and the main treatment strategy for improving AD symptoms is the inhibition of acetylcholinesterase (AChE) activity. In the present study, we aimed to identify potent AChE inhibitors from Cinnamomum loureirii extract via bioassay-guided fractionation. We demonstrated that the most potent AChE inhibitor present in the C. loureirii extract was 2,4-bis(1,1-dimethylethyl)phenol. To confirm the antiamnesic effects of the ethanol extract of C. loureirii, mice were intraperitoneally injected with the neurotoxin trimethyltin (2.5 mg/kg) to induce cognitive dysfunction, and performance in the Y-maze and passive avoidance tests was assessed. Treatment with C. loureirii extract significantly improved performance in both behavioral tests, suggesting that this extract may be neuroprotective and therefore beneficial in preventing or ameliorating the degenerative processes of AD, potentially by restoring cholinergic function. PMID:27374288

  10. Blocked Enzymatic Etching of Gold Nanorods: Application to Colorimetric Detection of Acetylcholinesterase Activity and Its Inhibitors.

    Saa, Laura; Grinyte, Ruta; Sánchez-Iglesias, Ana; Liz-Marzán, Luis M; Pavlov, Valeri

    2016-05-01

    The anisotropic morphology of gold nanorods (AuNRs) has been shown to lead to nonuniform ligand distribution and preferential etching through their tips. We have recently demonstrated that this effect can be achieved by biocatalytic oxidation with hydrogen peroxide, catalyzed by the enzyme horseradish peroxidase (HRP). We report here that modification of AuNRs with thiol-containing organic molecules such as glutathione and thiocholine hinders enzymatic AuNR etching. Higher concentrations of thiol-containing molecules in the reaction mixture gradually decrease the rate of enzymatic etching, which can be monitored by UV-vis spectroscopy through changes in the AuNR longitudinal plasmon band. This effect can be applied to develop novel optical assays for acetylcholinesterase (AChE) activity. The biocatalytic hydrolysis of acetylthiocholine by AChE yields thiocholine, which prevents enzymatic AuNR etching in the presence of HRP. Additionally, the same bioassay can be used for the detection of nanomolar concentrations of AChE inhibitors such as paraoxon and galanthamine. PMID:27070402

  11. Morphometry and acetylcholinesterase activity of the myenteric plexus of the wild mouse Calomys callosus

    L.B.M. Maifrino

    1997-05-01

    Full Text Available The myenteric plexus of the digestive tract of the wild mouse Calomys callosus was examined using a histochemical method that selectively stains nerve cells, and the acetylcholinesterase (AChE histochemical technique in whole-mount preparations. Neuronal density was 1,500 ± 116 neurons/cm2 (mean ± SEM in the esophagus, 8,900 ± 1,518 in the stomach, 9,000 ± 711 in the jejunum and 13,100 ± 2,089 in the colon. The difference in neuronal density between the esophagus and other regions was statistically significant. The neuron profile area ranged from 45 to 1,100 µm2. The difference in nerve cell size between the jejunum and other regions was statistically significant. AChE-positive nerve fibers were distributed within the myenteric plexus which is formed by a primary meshwork of large nerve bundles and a secondary meshwork of finer nerve bundles. Most of the nerve cells displayed AChE activity in the cytoplasm of different reaction intensities. These results are important in order to understand the changes occurring in the myenteric plexus in experimental Chagas' disease

  12. Design and prediction of new acetylcholinesterase inhibitor via quantitative structure activity relationship of huprines derivatives.

    Zhang, Shuqun; Hou, Bo; Yang, Huaiyu; Zuo, Zhili

    2016-05-01

    Acetylcholinesterase (AChE) is an important enzyme in the pathogenesis of Alzheimer's disease (AD). Comparative quantitative structure-activity relationship (QSAR) analyses on some huprines inhibitors against AChE were carried out using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and hologram QSAR (HQSAR) methods. Three highly predictive QSAR models were constructed successfully based on the training set. The CoMFA, CoMSIA, and HQSAR models have values of r (2) = 0.988, q (2) = 0.757, ONC = 6; r (2) = 0.966, q (2) = 0.645, ONC = 5; and r (2) = 0.957, q (2) = 0.736, ONC = 6. The predictabilities were validated using an external test sets, and the predictive r (2) values obtained by the three models were 0.984, 0.973, and 0.783, respectively. The analysis was performed by combining the CoMFA and CoMSIA field distributions with the active sites of the AChE to further understand the vital interactions between huprines and the protease. On the basis of the QSAR study, 14 new potent molecules have been designed and six of them are predicted to be more active than the best active compound 24 described in the literature. The final QSAR models could be helpful in design and development of novel active AChE inhibitors. PMID:26832327

  13. Determination of Antioxidant, Anticholinesterase, Tyrosinase Inhibitory Activities and Fatty Acid Profiles of 10 Anatolian Klasea Cass. Species

    Gülsen Tel

    2015-08-01

    Full Text Available In search of new natural fatty acid sources, extract of 10 different Turkish Klasea species were studies. Fatty acids of Klasea species were studied by GC and GC-MSD. Oleic acid (4.8-45.8%, palmitic acid (15.6-51.8%, linoleic acid (0.3-45.5%, palmitoleic acid (0.8-28.4% and linolenic acid (15.6-34.6% were the main fatty acids elucidated. All extracts were also subjected to acetylcholinesterase, butyrylcholinesterase, tyrosinase, β-carotene-linoleic acid, DPPH • scavenging, CUPRAC and ferrous ion-chelating ability activities. Total flavonoid and phenolic contents were determined as quercetin and pyrocatechol equivalents. All extracts showed significant antioxidant activity in all tests, except hexane extracts of K. serratuloides and K. cerinthifolia that showed weak inhibition against BChE and AChE. The hexane extract of K. coriaceae and methanol extract of K. serratuloides exhibited notable tyrosinase inhibitory activity.

  14. Molecular Basis of Inhibitory Activities of Berberine against Pathogenic Enzymes in Alzheimer's Disease

    Hong-Fang Ji; Liang Shen

    2012-01-01

    The natural isoquinoline alkaloid berberine possesses potential to treat Alzheimer's disease (AD) by targeting multiple pathogenic factors. In the present study, docking simulations were performed to gain deeper insights into the molecular basis of berberine's inhibitory effects against the important pathogenic enzymes of AD, that is, acetylcholinesterase, butyrylcholinesterase, and two isoforms of monoamine oxidase. It was found that the theoretical binding affinities of berberine to the fou...

  15. Phenolic profiles, antioxidant capacity, and acetylcholinesterase inhibitory activity of eight South African seaweeds

    Rengasamy, K.R.R.; Amoo, S.O.; Aremu, A.O.; Stirk, W.A.; Grúz, Jiří; Šubrtová, Michaela; Doležal, Karel; van Staden, J.

    2015-01-01

    Roč. 27, č. 4 (2015), s. 1599-1605. ISSN 0921-8971 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Alzheimer's disease * AChE inhibitors * Phenolics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.559, year: 2014

  16. Chemical Constituents from Sonneratia ovata Backer and their in vitro Cytotoxicity and Acetylcholinesterase Inhibitory Activities

    Nguyen, Thi Hoai Thu; Huu Viet Thong, Phamb; Nguyen, KimTuyen Phamc;

    2015-01-01

    Sonneratia ovata Backer, Sonneratiaceae, is a widespread plant in mangrove forests in Vietnam, Cambodia, Thailand, Indonesia. Sonneratia ovata’s chemical composition remains mostly unknown. Therefore, we now report on the structural elucidation of three new phenolics, sonnerphenolic A (1), sonner......Sonneratia ovata Backer, Sonneratiaceae, is a widespread plant in mangrove forests in Vietnam, Cambodia, Thailand, Indonesia. Sonneratia ovata’s chemical composition remains mostly unknown. Therefore, we now report on the structural elucidation of three new phenolics, sonnerphenolic A (1...

  17. Transcriptional activity of acetylcholinesterase gene is regulated by DNA methylation during C2C12 myogenesis.

    Lau, Kei M; Gong, Amy G W; Xu, Miranda L; Lam, Candy T W; Zhang, Laura M L; Bi, Cathy W C; Cui, D; Cheng, Anthony W M; Dong, Tina T X; Tsim, Karl W K; Lin, Huangquan

    2016-07-01

    The expression of acetylcholinesterase (AChE), an enzyme hydrolyzes neurotransmitter acetylcholine at vertebrate neuromuscular junction, is regulated during myogenesis, indicating the significance of muscle intrinsic factors in controlling the enzyme expression. DNA methylation is essential for temporal control of myogenic gene expression during myogenesis; however, its role in AChE regulation is not known. The promoter of vertebrate ACHE gene carries highly conserved CG-rich regions, implying its likeliness to be methylated for epigenetic regulation. A DNA methyltransferase inhibitor, 5-azacytidine (5-Aza), was applied onto C2C12 cells throughout the myotube formation. When DNA methylation was inhibited, the promoter activity, transcript expression and enzymatic activity of AChE were markedly increased after day 3 of differentiation, which indicated the putative role of DNA methylation. By bisulfite pyrosequencing, the overall methylation rate was found to peak at day 3 during C2C12 cell differentiation; a SP1 site located at -1826bp upstream of mouse ACHE gene was revealed to be heavily methylated. The involvement of transcriptional factor SP1 in epigenetic regulation of AChE was illustrated here: (i) the SP1-driven transcriptional activity was increased in 5-Aza-treated C2C12 culture; (ii) the binding of SP1 onto the SP1 site of ACHE gene was fully blocked by the DNA methylation; and (iii) the sequence flanking SP1 sites of ACHE gene was precipitated by chromatin immuno-precipitation assay. The findings suggested the role of DNA methylation on AChE transcriptional regulation and provided insight in elucidating the DNA methylation-mediated regulatory mechanism on AChE expression during muscle differentiation. PMID:27021952

  18. Effect of ions on the activity of brain acetylcholinesterase from tropical fish

    Caio Rodrigo Dias Assis

    2015-07-01

    Full Text Available Objective: To investigate the effect of ions on brain acetylcholinesterase (AChE; EC 3.1.1.7 activities from economic important fish [pirarucu, Arapaima gigas; tambaqui, Colossoma macropomum; cobia, Rachycentron canadum (R. canadum and Nile tilapia, Oreochromis niloticus (O. niloticus] comparing with a commercial enzyme from electric eel [Electrophorus electricus (E. electricus]. Methods: The in vitro exposure was performed at concentrations ranging from 0.001 to 10 mmol/L (except for ethylene diamine tetraacetic acid; up to 150 mmol/L. Inhibition kinetics on R. canadum and O. niloticus were also observed through four methods (Michaelis-Menten, Lineweaver-Burk, Dixon and Cornish-Bowden plots in order to investigate the type of inhibition produced by some ions. Results: Hg 2+ , As 3+ , Cu 2+ , Zn 2+ , Cd 2+ caused inhibition in all the species under study. Ca 2+ , Mg 2+ and Mn 2+ induced slight activation in R. canadum enzyme while Pb 2+ , Ba 2+ , Fe 2+ , Li + inhibited the AChE from some of the analyzed species. The lowest IC 50 and Ki values were estimated for E. electricus AChE in presence of Hg 2+ , Pb 2+ , Zn 2+ . Under our experimental conditions, the results for R. canadum and O. niloticus, As 3+ , Cu 2+ , Cd 2+ , Pb 2+ and Zn 2+ showed a non- competitive/mixed-type inhibition, while Hg 2+ inhibited the enzyme in a mixed/competitive- like manner. Conclusions: E. electricus AChE activity was affected by ten of fifteen ions under study showing that this enzyme could undergo interference by these ions when used as pesticide biosensor in environmental analysis. This hindrance would be less relevant for the crude extracts.

  19. Rapid eye movement sleep deprivation induces an increase in acetylcholinesterase activity in discrete rat brain regions

    Benedito M.A.C.

    2001-01-01

    Full Text Available Some upper brainstem cholinergic neurons (pedunculopontine and laterodorsal tegmental nuclei are involved in the generation of rapid eye movement (REM sleep and project rostrally to the thalamus and caudally to the medulla oblongata. A previous report showed that 96 h of REM sleep deprivation in rats induced an increase in the activity of brainstem acetylcholinesterase (Achase, the enzyme which inactivates acetylcholine (Ach in the synaptic cleft. There was no change in the enzyme's activity in the whole brain and cerebrum. The components of the cholinergic synaptic endings (for example, Achase are not uniformly distributed throughout the discrete regions of the brain. In order to detect possible regional changes we measured Achase activity in several discrete rat brain regions (medulla oblongata, pons, thalamus, striatum, hippocampus and cerebral cortex after 96 h of REM sleep deprivation. Naive adult male Wistar rats were deprived of REM sleep using the flower-pot technique, while control rats were left in their home cages. Total, membrane-bound and soluble Achase activities (nmol of thiocholine formed min-1 mg protein-1 were assayed photometrically. The results (mean ± SD obtained showed a statistically significant (Student t-test increase in total Achase activity in the pons (control: 147.8 ± 12.8, REM sleep-deprived: 169.3 ± 17.4, N = 6 for both groups, P<0.025 and thalamus (control: 167.4 ± 29.0, REM sleep-deprived: 191.9 ± 15.4, N = 6 for both groups, P<0.05. Increases in membrane-bound Achase activity in the pons (control: 171.0 ± 14.7, REM sleep-deprived: 189.5 ± 19.5, N = 6 for both groups, P<0.05 and soluble enzyme activity in the medulla oblongata (control: 147.6 ± 16.3, REM sleep-deprived: 163.8 ± 8.3, N = 6 for both groups, P<0.05 were also observed. There were no statistically significant differences in the enzyme's activity in the other brain regions assayed. The present findings show that the increase in Achase activity

  20. In vivo effects of metals on the acetylcholinesterase activity of the Perna perna mussel’s digestive gland

    Afonso Celso Dias Bainy; Marisa Helena Gennari de Medeiros; Paolo Di Mascio; Eduardo Alves de Almeida

    2006-01-01

    It has been demonstrated that the enzyme acetylcholinesterase (AChE) is strongly inhibited by organophosphate and carbamate pesticides, and also by metals. However, recent reports indicate that some metals can activate AChE during acute exposure. In this work, we were interested in evaluating the effect of trace metal exposure (12, 24, 72 and 120 h) on the AChE activity of Perna perna mussel’s digestive gland. Mussels exposed to Fe or Cu showed no changes in AChE activity during the whole per...

  1. Comparison of the oxime-induced reactivation of rhesus monkey, swine and guinea pig erythrocyte acetylcholinesterase following inhibition by sarin or paraoxon, using a perfusion model for the real-time determination of membrane-bound acetylcholinesterase activity.

    Herkert, Nadja,; Lallement, Guy; Clarençon, Didier; Thiermann, Horst; Worek, Franz

    2009-01-01

    Recently, a dynamically working in vitro model with real-time determination of membrane-bound human acetylcholinesterase (AChE) activity was shown to be a versatile model to investigate oxime-induced reactivation kinetics of organophosphate- (OP) inhibited enzyme. In this assay, AChE was immobilized on particle filters which were perfused with acetylthiocholine, Ellman's reagent and phosphate buffer. Subsequently, AChE activity was continuously analyzed in a flow-through detector. Now, it was...

  2. Effects of Roundup Transorb on fish: hematology, antioxidant defenses and acetylcholinesterase activity.

    Modesto, Kathya A; Martinez, Cláudia B R

    2010-10-01

    Roundup Transorb(RDT) is a glyphosate-based herbicide containing a mixture of surfactants. The objective of this work was to evaluate the effects of this herbicide on the Neotropical fish Prochilodus lineatus. Juvenile fish were acutely exposed (6, 24 and 96 h) to 1 mg L(-1) of RDT (RDT 1), 5 mg L(-1) of RDT (RDT 5) or only water (control) and blood samples for hematological analysis, liver for antioxidants analysis, and brain and muscle for acetylcholinesterase (AChE) determination, were collected. RDT effects were more evident in fish exposed to the higher concentration of the herbicide. Hematologic alterations appeared only after 96 h exposure, when fish showed an increase in the hematocrit and in the number of both red and white blood cells. After 6h exposure fish showed a transient reduction in superoxide dismutase and catalase activity. RDT also inhibited glutathione-S-transferase, after 6 and 24h of exposure. The reduction in these enzymes is probably related to the occurrence of lipid peroxidation (LPO) in fish exposed to the herbicide for 6h. LPO returned to control levels after 24 and 96 h exposure to RDT, when fish showed an increased activity of glutathione peroxidase. The content of reduced glutathione also increased after 96 h exposure. Thus, after 24 and 96 h the antioxidant defenses were apparently enough to combat ROS, preventing the occurrence of oxidative damage. The exposure to RDT for 96 h led to an inhibition of AChE in brain and muscle at rates which may not be considered a life-threatening situation. PMID:20684975

  3. Measurement of acetylcholinesterase (AChE) activity in living brain by positron emission tomography (PET)

    Central cholinergic neuronal system has been known to be related to learning and memory, and its deficit is found in the brain of Alzheimer's disease (AD) and other degenerative disorders. Postmortem studies have shown that acetylcholinesterase (AChE), one of biochemical markers of central cholinergic nerve system, is consistently reduced in the cerebral cortex of patients with Alzheimer's disease (AD). Non-invasive mapping and/or measuring AChE activity in the living brain by positron emission tomography (PET) would be a useful tool for assessment of cholinergic dysfunction in AD and other disorders, and provide a direct method for validation of therapeutic efficacy of drugs, AChE inhibitors. We have challenged to measure AChE activity using tracers of substrate type, radiolabelled acetylcholine analogs, which are lipophilic enough to go across blood brain barrier and are metabolically trapped by AChE in the brain. The analogs designed, N-methylpiperidyl esters, were evaluated in terms of their metabolic rate and specificity against AChE. Studies examining the response to AChE activity showed metabolic accumulation of some analogs responded well to changes in cortical AChE activity in an animal model of AD. The study was further applied to living human by PET using [11C]N-methylpiperidyl-4-acetate (MP4A), which was chosen on the basis of its reactivity and specificity suitable for the human cortical AChE. Regional cerebral metabolic rate of MP4A reflecting AChE activity was quantitatively determined using three compartment model analysis of dynamic PET data and the arterial input function obtained by TLC-radioluminography or plasma samples. The kinetic analyses showed that AChE activities estimated were well agree with those of postmortem examination in cerebral cortices and thalamus in healthy subjects, and that there was significant reduction of cortical AChE activity in patients with AD. The results suggest feasibility of the present method for assessing ACh

  4. 3,4-Methylenedioxymethamphetamine (MDMA) Abuse Markedly Inhibits Acetylcholinesterase Activity and Induces Severe Oxidative Damage and Liperoxidative Damage

    2003-01-01

    Objective To investigate whether 3,4-methylenedioxymethamphetamine (MDMA) abuse produces another neurotoxicity which may significantly inhibit the acetylcholinesterase activity and result in severe oxidative damage and liperoxidative damage to MDMA abusers. Methods 120 MDMA abusers (MA) and 120 healthy volunteers (HV) were enrolled in an independent sample control design, in which the levels of lipoperoxide (LPO) in plasma and erythrocytes as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and acetylcholinesterase (AChE) in erythrocytes were determined by spectrophotometric methods. Results Compared with the average values of biochemical parameters in the HV group, those of LPO in plasma and erythrocytes in the MA group were significantly increased (P<0.0001), while those of SOD, CAT, GPX and AChE in erythrocytes in the MA group were significantly decreased (P<0.0001). The Pearson product-moment correlation analysis between the values of AChE and biochemical parameters in 120 MDMA abusers showed that significant linear negative correlation was present between the activity of AChE and the levels of LPO in plasma and erythrocytes (P<0.0005-0.0001), while significant linear positive correlation was observed between the activity of AchE and the activities of SOD, CAT and GPX (P<0.0001). The reliability analysis for the above biochemical parameters reflecting oxidative and lipoperoxidative damages in MDMA abusers suggested that the reliability coefficient (alpha) was 0.8124, and that the standardized item alpha was 0.9453. Conclusion The findings in the present study suggest that MDMA abuse can induce another neurotoxicity that significantly inhibits acetylcholinesterase activity and aggravates a series of free radical chain reactions and oxidative stress in the bodies of MDMA abusers, thereby resulting in severe neural, oxidative and lipoperoxidative damages in MDMA abusers.

  5. Molecular Dynamics of Acetylcholinesterase

    Shen, T Y.; Tai, Kaihsu; Henchman, Richard H.; Mccammon, Andy

    2002-06-01

    Molecular dynamics simulations are leading to a deeper understanding of the activity of the enzyme acetylcholinesterase. Simulations have shown how breathing motions in the enzyme facilitate the displacement of substrate from the surface of the enzyme to the buried active site. The most recent work points to the complex and spatially extensive nature of such motions and suggests possible modes of regulation of the activity of the enzyme.

  6. Subchronic atrazine exposure changes defensive behaviour profile and disrupts brain acetylcholinesterase activity of zebrafish.

    Schmidel, Ademir J; Assmann, Karla L; Werlang, Chariane C; Bertoncello, Kanandra T; Francescon, Francini; Rambo, Cassiano L; Beltrame, Gabriela M; Calegari, Daiane; Batista, Cibele B; Blaser, Rachel E; Roman Júnior, Walter A; Conterato, Greicy M M; Piato, Angelo L; Zanatta, Leila; Magro, Jacir Dal; Rosemberg, Denis B

    2014-01-01

    Animal behaviour is the interaction between environment and an individual organism, which also can be influenced by its neighbours. Variations in environmental conditions, as those caused by contaminants, may lead to neurochemical impairments altering the pattern of the behavioural repertoire of the species. Atrazine (ATZ) is an herbicide widely used in agriculture that is frequently detected in surface water, affecting non-target species. The zebrafish is a valuable model organism to assess behavioural and neurochemical effects of different contaminants since it presents a robust behavioural repertoire and also all major neurotransmitter systems described for mammalian species. The goal of this study was to evaluate the effects of subchronic ATZ exposure in defensive behaviours of zebrafish (shoaling, thigmotaxis, and depth preference) using the split depth tank. Furthermore, to investigate a putative role of cholinergic signalling on ATZ-mediated effects, we tested whether this herbicide alters acetylcholinesterase (AChE) activity in brain and muscle preparations. Fish were exposed to ATZ for 14days and the following groups were tested: control (0.2% acetone) and ATZ (10 and 1000μg/L). The behaviour of four animals in the same tank was recorded for 6min and biological samples were prepared. Our results showed that 1000μg/L ATZ significantly increased the inter-fish distance, as well as the nearest and farthest neighbour distances. This group also presented an increase in the shoal area with decreased social interaction. No significant differences were detected for the number of animals in the shallow area, latency to enter the shallow and time spent in shallow and deep areas of the apparatus, but the ATZ 1000 group spent significantly more time near the walls. Although ATZ did not affect muscular AChE, it significantly reduced AChE activity in brain. Exposure to 10μg/L ATZ did not affect behaviour or AChE activity. These data suggest that ATZ impairs defensive

  7. Anti-acetylcholinesterase and Antioxidant Activity of Essential Oils from Hedychium gardnerianum Sheppard ex Ker-Gawl

    José Silvino Rosa

    2012-03-01

    Full Text Available Acetylcholinesterase inhibition, antioxidant and cytotoxic activities of Hedychium gardnerianum leaf essential oils from S. Miguel Island were determined. All the oils inhibited acetylcholinesterase, with IC50 values of approximately 1 mg/mL, showing no statistical differences between collection sites. Three oils presented mixed inhibition, whilst one was almost truly competitive. This activity can be attributed to the presence of sesquiterpenes, which constituted more than 60% of the composition of the oils. Regarding the antioxidant activity as measured by the DPPH method, all the oils presented activities similar to reference compounds, although with statistical differences between collection sites. Cytotoxicity measured using Artemia salina classified these oils as moderately toxic, with LC50 values ranging from 300 to 500 µg/mL. These results indicate a possible application of these oils in aromatherapy as coadjuvants in the treatment of cognitive diseases such as Alzheimer, since they may contribute to increase acetylcholine in cholinergic neurons and simultaneously fight deleterious oxidations responsible by neurological degeneration.

  8. Possibility of Acetylcholinesterase Overexpression in Alzheimer Disease Patients after Therapy with Acetylcholinesterase Inhibitors

    Alžběta Kračmarová

    2015-08-01

    Full Text Available Acetylcholinesterase is an enzyme responsible for termination of excitatory transmission at cholinergic synapses by the hydrolyzing of a neurotransmitter acetylcholine. Nowadays, other functions of acetylcholinesterase in the organism are considered, for example its role in regulation of apoptosis. Cholinergic nervous system as well as acetylcholinesterase activity is closely related to pathogenesis of Alzheimer disease. The mostly used therapy of Alzheimer disease is based on enhancing cholinergic function using inhibitors of acetylcholinesterase like rivastigmine, donepezil or galantamine. These drugs can influence not only the acetylcholinesterase activity but also other processes in treated organism. The paper is aimed mainly on possibility of increased expression and protein level of acetylcholinesterase caused by the therapy with acetylcholinesterase inhibitors.

  9. Acetylcholinesterase inhibition, antioxidant activity and toxicity of Peumus boldus water extracts on HeLa and Caco-2 cell lines.

    Falé, P L; Amaral, F; Amorim Madeira, P J; Sousa Silva, M; Florêncio, M H; Frazão, F N; Serralheiro, M L M

    2012-08-01

    This work aimed to study the inhibition on acetylcholinesterase activity (AChE), the antioxidant activity and the toxicity towards Caco-2 and HeLa cells of aqueous extracts of Peumus Boldus. An IC(50) value of 0.93 mg/mL, for AChE inhibition, and EC(50) of 18.7 μg/mL, for the antioxidant activity, was determined. This activity can be attributed to glycosylated flavonoid derivatives detected, which were the main compounds, although boldine and other aporphine derivatives were also present. No changes in the chemical composition or the biochemical activities were found after gastrointestinal digestion. Toxicity of P. boldus decoction gave an IC(50) value 0.66 mg/mL for HeLa cells, which caused significant changes in the cell proteome profile. PMID:22617353

  10. Lipoxygenase inhibitory activity of Cuspidaria pulchra and isolated compounds.

    Alvarenga, Tavane A; Bertanha, Camila S; de Oliveira, Pollyanna F; Tavares, Denise C; Gimenez, Valéria M M; Silva, Márcio L A; Cunha, Wilson R; Januário, Ana H; Pauletti, Patrícia M

    2015-01-01

    This work evaluated the in vitro inhibitory activity of the crude ethanolic extract from the aerial parts of Cuspidaria pulchra (Cham.) L.G. Lohmann against 15-lipoxygenase (15-LOX). The bioassay-guided fractionation of the n-butanol fraction, which displayed the highest activity, led to the isolation of three compounds: caffeoylcalleryanin (1), verbascoside (2) and 6-hydroxyluteolin-7-O-β-glucoside (3). Assessment of the ability of the isolated compounds to inhibit 15-LOX revealed that compounds 1, 2 and 3 exerted strong 15-LOX inhibitory activity; IC50 values were 1.59, 1.76 and 2.35 μM respectively. The XTT assay showed that none of the isolated compounds seemed to be significantly toxic. PMID:25428032

  11. In vivo effects of metals on the acetylcholinesterase activity of the Perna perna mussel’s digestive gland

    Afonso Celso Dias Bainy

    2006-03-01

    Full Text Available It has been demonstrated that the enzyme acetylcholinesterase (AChE is strongly inhibited by organophosphate and carbamate pesticides, and also by metals. However, recent reports indicate that some metals can activate AChE during acute exposure. In this work, we were interested in evaluating the effect of trace metal exposure (12, 24, 72 and 120 h on the AChE activity of Perna perna mussel’s digestive gland. Mussels exposed to Fe or Cu showed no changes in AChE activity during the whole period. Mussels exposed to Cd for 72 h or to Pb for 12 hours showed higher AChE activity than the control group. Based on these results, we hypothesize that under acute exposure, metals might interact with acetylcholine receptors, thereby affecting their binding efficiency and leading to a response involving an initial increase in AChE synthesis.

  12. A simple radiometric in vitro assay for acetylcholinesterase inhibitors

    A radiometric method for screening acetylcholinesterase inhibitors has been described. The method is based on the production of [14C]carbon dioxide from the hydrolysis of acetylcholine. The inhibitory concentration at 50% (IC50) values for several known acetylcholinesterase inhibitors were in agreement with literature values. The new radiometric method is simple, inexpensive, and has the potential for automation

  13. Acetylcholinesterase-inhibiting Alkaloids from Zephyranthes concolor

    Sebastien Arseneau

    2011-11-01

    Full Text Available The bulbs and aerial parts of Zephyranthes concolor (Lindl. Benth. & Hook. f. (Amaryllidaceae, an endemic species to Mexico, were found to contain the alkaloids chlidanthine, galanthamine, galanthamine N-oxide, lycorine, galwesine, and epinorgalanthamine. Since currently only partial and low resolution 1H-NMR data for chlidanthine acetate are available, and none for chlidanthine, its 1D and 2D high resolution 1H- and 13C-NMR spectra were recorded. Unambiguous assignations were achieved with HMBC, and HSQC experiments, and its structure was corroborated by X-ray diffraction. Minimum energy conformation for structures of chlidanthine, and its positional isomer galanthamine, were calculated by molecular modelling. Galanthamine is a well known acetylcholinesterase inhibitor; therefore, the isolated alkaloids were tested for this activity. Chlidanthine and galanthamine N-oxide inhibited electric eel acetylcholinesterase (2.4 and 2.6 × 10−5 M, respectively, indicating they are about five times less potent than galanthamine, while galwesine was inactive at 10−3 M. Inhibitory activity of HIV-1 replication, and cytotoxicity of the isolated alkaloids were evaluated in human MT-4 cells; however, the alkaloids showed poor activity as compared with standard anti-HIV drugs, but most of them were not cytotoxic.

  14. Anti-acetylcholinesterase and Antioxidant Activities of Inhaled Juniper Oil on Amyloid Beta (1-42)-Induced Oxidative Stress in the Rat Hippocampus.

    Cioanca, Oana; Hancianu, Monica; Mihasan, Marius; Hritcu, Lucian

    2015-05-01

    Juniper volatile oil is extracted from Juniperus communis L., of the Cupressaceae family, also known as common juniper. Also, in aromatherapy the juniper volatile oil is used against anxiety, nervous tension and stress-related conditions. In the present study, we identified the effects of the juniper volatile oil on amyloid beta (1-42)-induced oxidative stress in the rat hippocampus. Rats received a single intracerebroventricular injection of amyloid beta (1-42) (400 pmol/rat) and then were exposed to juniper volatile oil (200 μl, either 1 or 3 %) for controlled 60 min period, daily, for 21 continuous days. Also, the antioxidant activity in the hippocampus was assessed using superoxide dismutase, glutathione peroxidase and catalase specific activities, the total content of the reduced glutathione, protein carbonyl and malondialdehyde levels. Additionally, the acetylcholinesterase activity in the hippocampus was assessed. The amyloid beta (1-42)-treated rats exhibited the following: increase of the acetylcholinesterase, superoxide dismutase and catalase specific activities, decrease of glutathione peroxidase specific activity and the total content of the reduced glutathione along with an elevation of malondialdehyde and protein carbonyl levels. Inhalation of the juniper volatile oil significantly decreases the acetylcholinesterase activity and exhibited antioxidant potential. These findings suggest that the juniper volatile oil may be a potential candidate for the development of therapeutic agents to manage oxidative stress associated with Alzheimer's disease through decreasing the activity of acetylcholinesterase and anti-oxidative mechanism. PMID:25743585

  15. Effect of the methanol leaves extract of Clinacanthus nutans on the activity of acetylcholinesterase in male mice

    Lau KW; Lee SK; Chin JH

    2014-01-01

    Objective:To evaluate thein vivoeffect of14 d repeatedly oral administration ofClinacanthus nutans(C. nutans) methanol leaves extract(250 mg/kg,500 mg/kg and1000 mg/kg bw) on the acetylcholinesterase(AChE) activity in maleBalb/C mice.Method:First group was served as control group, orally treated with distilled water as vehicle and group2-4 were orally treated with a single daily dose of250 mg/kg,500 mg/kg and1000 mg/kg bw ofC. nutans extract, respectively for14 d.Each group consisted of six animals(n=6).The activity of acetylcholinesterase in brain, liver, kidney and heart of mice was determined according toEllman method(1961).Results:From the results obtained, theAChE activity was found to be highest in mice liver, followed by brain, kidney and heart.Methanol extract ofC. nutans leaves at250 mg/kg(P<0.001),500 mg/kg(P<0.001) and1000 mg/kg(P<0.001) showed a significant increase in theAChE activity in mice kidney, liver and heart.On the other hand, theAChE activity obtained from the mice brain showed insignificant difference between the control group and treatment group.However, there was no abnormal behavioural change and adverse effect related to the central nervous system observed in all treated mice during14 d experimentation period.Conclusion:In conclusion,14 d oral administration ofC. nutans was able to modulate cholinergic neurotransmission by activating AChE activity in mice kidney, liver and heart.Compounds that responsible for the induction of AChE activity in mice liver, heart and kidney and its mechanism needs to be elucidated.

  16. Photodestruction of acetylcholinesterase

    Ultraviolet irradiation of 11S acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7) produces a loss of tryptophan fluorescence which is best described as the sum of two separable first-order processes, one much more rapid than the other. In addition, the enzyme undergoes an all-or-none inactivation that is monotonically first order. Simultaneous with activity loss, photoscission takes place and results in a molecular weight drop. The extreme sensitivity of acetylcholinesterase to photodestruction upon photon absorption and the several events that follow it not only suggest that these findings might be a basis for a useful molecular probe of the structure of this enzyme, but also indicate that additional care should be taken when conducting spectroscopic studies in the uv region

  17. Tyrosinase, Acetyl- and Butyryl-Cholinesterase Inhibitory Activity of Stachys lavandulifolia Vahl (Lamiaceae and Its Major Constituents

    Rosa Tundis

    2014-09-01

    Full Text Available The n-hexane (HE, dichloromethane (DC, methanol (ME, ethanol 70% (ET, and methanol with Soxlhet apparatus (MS extracts of Stachys lavandulifolia aerial parts were screened for their potential tyrosinase, acetylcholinesterase (AChE and butyrylcholinesterase (BChE inhibitory activity. ET and MS inhibited tyrosinase with IC 50 values of 33.4 and 42.8 m g/mL, respectively. The phytochemical investigation of these extracts resulted in the isolation of the known compounds monomelittoside (1, melittoside (2, 5-allosyloxy-aucubin (3, acteoside (4 and arbutin (5. The HE extract, characterized by germacrene D, b -pinene, b -myrcene, and trans-caryophyllene as main constituents, showed the highest AChE inhibitory activity with an IC 50 value of 13.7 m g/mL while DC extract was the most active against BChE (IC 50 value of 143.9 m g/mL. The diterpene stachysolone (6 was isolated from this extract. The antioxidant properties were also investigated by four in vitro methods (DPPH, ABTS, FRAP and b -carotene bleaching tests.

  18. Presenilin 1 Interacts with Acetylcholinesterase and Alters Its Enzymatic Activity and Glycosylation▿

    Silveyra, María-Ximena; Evin, Geneviève; Montenegro, María-Fernanda; Vidal, Cecilio J; Martínez, Salvador; Culvenor, Janetta G.; Sáez-Valero, Javier

    2008-01-01

    Presenilin 1 (PS1) plays a critical role in the γ-secretase processing of the amyloid precursor protein to generate the β-amyloid peptide, which accumulates in plaques in the pathogenesis of Alzheimer's disease (AD). Mutations in PS1 cause early onset AD, and proteins that interact with PS1 are of major functional importance. We report here the coimmunoprecipitation of PS1 and acetylcholinesterase (AChE), an enzyme associated with amyloid plaques. Binding occurs through PS1 N-terminal fragmen...

  19. Behavioral swimming effects and acetylcholinesterase activity changes in Jenynsia multidentata exposed to chlorpyrifos and cypermethrin individually and in mixtures.

    Bonansea, Rocío Inés; Wunderlin, Daniel Alberto; Amé, María Valeria

    2016-07-01

    The pesticides cypermethrin (CYP) and chlorpyrifos (CPF) were found together in water bodies located in agricultural and urban areas. However, the impact to non-target biota from exposure to mixtures has received little attention. In the current study, we evaluated changes in swimming behavior and cholinesterase enzymes activity in Jenynsia multidentata, to investigate the possible effects of these insecticides individually and in mixtures. Moreover, differences between technical and commercial mixtures of the pesticides were evaluated. Females of J. multidentata were exposed over 96-h to CYP (0.04 and 0.4µgL(-1)), CPF (0.4 and 4µgL(-1)), individually and in a technical and commercial mixtures. Swimming behavior was recorded after 24h and 96h of exposure. Also, we measured cholinesterase enzymes activity in brain and muscle after 96h of exposure. Exposure to CYP increased the exploratory activity of J. multidentata in the upper area of the aquarium. Fish exposed to CPF (4µg L(-1)) showed a decrease in swimming activity and an increase in the time spent at the bottom of the aquarium. Interestingly, fish exposed to the technical and commercial mixture of CYP and CPF displayed a different behavior based on the concentration of exposure. Low concentration of pesticides elicited an increase in J. multidentata swimming activity with preference for the upper area of the aquarium, and high concentrations caused decrease in swimming activity with preference for the bottom area of the aquarium. Based on the response of cholinesterase enzymes, acetylcholinesterase in muscle was more sensitive to exposure to CYP, CPF and their mixtures than in brain. A decrease in swimming behavior correlates significantly with the inhibition of acetylcholinesterase activity in muscle of J. multidentata exposed to high concentrations of pesticides. These results draw attention to the need of more studies on the potential ecotoxicological impact of pesticides and its mixtures at

  20. Plants from Brazilian Cerrado with potent tyrosinase inhibitory activity.

    Paula Monteiro Souza

    Full Text Available The increased amount of melanin leads to skin disorders such as age spots, freckles, melasma and malignant melanoma. Tyrosinase is known to be the key enzyme in melanin production. Plants and their extracts are inexpensive and rich resources of active compounds that can be utilized to inhibit tyrosinase as well as can be used for the treatment of dermatological disorders associated with melanin hyperpigmentation. Using in vitro tyrosinase inhibitory activity assay, extracts from 13 plant species from Brazilian Cerrado were evaluated. The results showed that Pouteria torta and Eugenia dysenterica extracts presented potent in vitro tyrosinase inhibition compared to positive control kojic acid. Ethanol extract of Eugenia dysenterica leaves showed significant (p<0.05 tyrosinase inhibitory activity exhibiting the IC₅₀ value of 11.88 µg/mL, compared to kojic acid (IC₅₀ value of 13.14 µg/mL. Pouteria torta aqueous extract leaves also showed significant inhibitory activity with IC₅₀ value of 30.01 µg/mL. These results indicate that Pouteria torta and Eugenia dysenterica extracts and their isolated constituents are promising agents for skin-whitening or antimelanogenesis formulations.

  1. Effects of sub-lethal neurite outgrowth inhibitory concentrations of chlorpyrifos oxon on cytoskeletal proteins and acetylcholinesterase in differentiating N2a cells

    Flaskos, J., E-mail: flaskos@vet.auth.gr [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Nikolaidis, E. [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Harris, W. [School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom); Sachana, M. [Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Hargreaves, A.J., E-mail: alan.hargreaves@ntu.ac.uk [School of Science and Technology, Nottingham Trent University, Clifton Lane, Nottingham NG11 8NS (United Kingdom)

    2011-11-15

    Previous work in our laboratory has shown that sub-lethal concentrations (1-10 {mu}M) of chlorpyrifos (CPF), diazinon (DZ) and diazinon oxon (DZO) inhibit the outgrowth of axon-like neurites in differentiating mouse N2a neuroblastoma cells concomitant with altered levels and/or phosphorylation state of axonal cytoskeleton and growth-associated proteins. The aim of the present work was to determine whether chlorpyrifos oxon (CPO) was capable of inhibiting N2a cell differentiation in a similar manner. Using experimental conditions similar to our previous work, sub-lethal concentrations (1-10 {mu}M) of CPO were found to inhibit N2a cell differentiation. However, unlike previous studies with DZ and DZO, there was a high level of sustained inhibition of acetylcholinesterase (AChE) in CPO treated cells. Impairment of neurite outgrowth was also associated with reduced levels of growth associated protein-43 and neurofilament heavy chain (NFH), and the distribution of NFH in cells stained by indirect immunofluorescence was disrupted. However, in contrast to previous findings for DZO, the absolute level of phosphorylated NFH was unaffected by CPO exposure. Taken together, the findings suggest that sub-lethal concentrations of CPO inhibit axon outgrowth in differentiating N2a cells and that this effect involves reduced levels of two proteins that play key roles in axon outgrowth and maintenance. Although the inhibition of neurite outgrowth is unlikely to involve AChE inhibition directly, further work will help to determine whether the persistent inhibition of AChE by CPO can account for the different effects induced by CPO and DZO on the levels of total and phosphorylated NFH. -- Highlights: Black-Right-Pointing-Pointer Sub-lethal levels of chlorpyrifos oxon inhibit neurite outgrowth in N2a cells Black-Right-Pointing-Pointer Acetylcholinesterase exhibits sustained inhibition throughout exposure Black-Right-Pointing-Pointer The levels of neurofilament heavy chain and GAP-43

  2. Effects of sub-lethal neurite outgrowth inhibitory concentrations of chlorpyrifos oxon on cytoskeletal proteins and acetylcholinesterase in differentiating N2a cells

    Previous work in our laboratory has shown that sub-lethal concentrations (1–10 μM) of chlorpyrifos (CPF), diazinon (DZ) and diazinon oxon (DZO) inhibit the outgrowth of axon-like neurites in differentiating mouse N2a neuroblastoma cells concomitant with altered levels and/or phosphorylation state of axonal cytoskeleton and growth-associated proteins. The aim of the present work was to determine whether chlorpyrifos oxon (CPO) was capable of inhibiting N2a cell differentiation in a similar manner. Using experimental conditions similar to our previous work, sub-lethal concentrations (1–10 μM) of CPO were found to inhibit N2a cell differentiation. However, unlike previous studies with DZ and DZO, there was a high level of sustained inhibition of acetylcholinesterase (AChE) in CPO treated cells. Impairment of neurite outgrowth was also associated with reduced levels of growth associated protein-43 and neurofilament heavy chain (NFH), and the distribution of NFH in cells stained by indirect immunofluorescence was disrupted. However, in contrast to previous findings for DZO, the absolute level of phosphorylated NFH was unaffected by CPO exposure. Taken together, the findings suggest that sub-lethal concentrations of CPO inhibit axon outgrowth in differentiating N2a cells and that this effect involves reduced levels of two proteins that play key roles in axon outgrowth and maintenance. Although the inhibition of neurite outgrowth is unlikely to involve AChE inhibition directly, further work will help to determine whether the persistent inhibition of AChE by CPO can account for the different effects induced by CPO and DZO on the levels of total and phosphorylated NFH. -- Highlights: ► Sub-lethal levels of chlorpyrifos oxon inhibit neurite outgrowth in N2a cells ► Acetylcholinesterase exhibits sustained inhibition throughout exposure ► The levels of neurofilament heavy chain and GAP-43 protein are reduced ► Neurofilament heavy chain forms aggregates in cell

  3. Acetylcholinesterase enzyme inhibitor activity of some novel pyrazinamide condensed 1,2,3,4-tetrahydropyrimidines

    Karthikeyan Elumalai

    2015-03-01

    Full Text Available A new series of some novel pyrazinamide condensed 1,2,3,4-tetrahydropyrimidines was prepared by reacting of N-(3-oxobutanoylpyrazine-2-carboxamide with urea/thiourea and appropriate aldehyde in the presence of catalytic amount of laboratory made p-toluenesulfonic acid as an efficient catalyst. Confirmation of the chemical structure of the synthesized compounds (4a–l was substantiated by TLC, different spectral data IR, 1H NMR, mass spectra and elemental analysis. The synthesized compounds were evaluated for acetyl and butyl cholinesterase (AChE and BuChE inhibitor activity. The titled compounds exhibited weak, moderate or high AChE and BuChE inhibitor activity. Especially, compound (4l showed the best AChE and BuChE inhibitory activity of all the 1,2,3,4-tetrahydropyrimidine derivatives, with an IC50 value of 0.11 μM and 3.4 μM.

  4. Inhibitory Effects of Resveratrol Analogs on Mushroom Tyrosinase Activity

    Nádia Rezende Barbosa Raposo; Adilson David da Silva; Raquel da Silva Teixeira; Gustavo Senra Gonçalves de Carvalho; Paula Rafaela Rocha; Danielle Cristina Zimmermann Franco

    2012-01-01

    Skin pigmentation disorders typically involve an overproduction or uneven distribution of melanin, which results in skin spots. Resveratrol can inhibit tyrosinase, the active enzyme in the synthesis of melanin, but it does not inhibit the synthesis of melanin to an extent that enables its use alone as a skin whitening agent in pharmaceutical formulations, so its use as a coadjuvant in treatment of hyperpigmentation is suggested. Six resveratrol analogs were tested for tyrosinase inhibitory ac...

  5. Wild Argentinian Amaryllidaceae, a New Renewable Source of the Acetylcholinesterase Inhibitor Galanthamine and Other Alkaloids

    Feresin, Gabriela E.; Jaume Bastida; Alejandro Tapia; German Roitman; Cristina Theoduloz; Strahil Berkov; Natalia B. Pigni; Javier E. Ortiz

    2012-01-01

    The Amaryllidaceae family is well known for its pharmacologically active alkaloids. An important approach to treat Alzheimer’s disease involves the inhibition of the enzyme acetylcholinesterase (AChE). Galanthamine, an Amaryllidaceae alkaloid, is an effective, selective, reversible, and competitive AchE inhibitor. This work was aimed at studying the alkaloid composition of four wild Argentinian Amarillydaceae species for the first time, as well as analyzing their inhibitory activity...

  6. Inhibitory effects of fruit juices on CYP3A activity.

    Kim, Hyunmi; Yoon, Yune-Jung; Shon, Ji-Hong; Cha, In-June; Shin, Jae-Gook; Liu, Kwang-Hyeon

    2006-04-01

    There have been very limited reports on the effects of commercial fruit juices on human CYP3A activity. Therefore, the inhibitory effects of readily available commercial fruit juices on midazolam 1'-hydroxylase activity, a marker of CYP3A, were evaluated in pooled human liver microsomes. The fruit juices investigated were black raspberry, black mulberry, plum, and wild grape. White grapefruit, pomegranate, and orange juice were used as positive and negative controls. The black mulberry juice showed the most potent inhibition of CYP3A except for grapefruit juice. The inhibition depended on the amount of a fruit juice added to the incubation mixture. The inhibitory potential of human CYP3A was in the order: grapefruit > black mulberry > wild grape > pomegranate > black raspberry. The IC(50) values of all fruit juices tested were reduced after preincubation with microsomes in the presence of the NADPH-generating system, suggesting that a mechanism-based inhibitory component was present in these fruit juices, as in the case of grapefruit. The results suggest that, like grapefruit juice, commercial fruit juices also have the potential to inhibit CYP3A-catalzyed midazolam 1'-hydroxylation. Therefore, in vivo studies investigating the interactions between fruit juices such as black mulberry and wild grape and CYP3A substrates are necessary to determine whether inhibition of CYP3A activity by fruit juices is clinically relevant. PMID:16415112

  7. Inhibition and Larvicidal Activity of Phenylpropanoids from Piper sarmentosum on Acetylcholinesterase against Mosquito Vectors and Their Binding Mode of Interaction

    Hematpoor, Arshia; Liew, Sook Yee; Chong, Wei Lim; Azirun, Mohd Sofian; Lee, Vannajan Sanghiran; Awang, Khalijah

    2016-01-01

    Aedes aegypti, Aedes albopictus and Culex quinquefasciatus are vectors of dengue fever and West Nile virus diseases. This study was conducted to determine the toxicity, mechanism of action and the binding interaction of three active phenylpropanoids from Piper sarmentosum (Piperaceae) toward late 3rd or early 4th larvae of above vectors. A bioassay guided-fractionation on the hexane extract from the roots of Piper sarmentosum led to the isolation and identification of three active phenylpropanoids; asaricin 1, isoasarone 2 and trans-asarone 3. The current study involved evaluation of the toxicity and acetylcholinesterase (AChE) inhibition of these compounds against Aedes aegypti, Aedes albopictus and Culex quinquefasciatus larvae. Asaricin 1 and isoasarone 2 were highly potent against Aedes aegypti, Aedes albopictus and Culex quinquefasciatus larvae causing up to 100% mortality at ≤ 15 μg/mL concentration. The ovicidal activity of asaricin 1, isoasarone 2 and trans-asarone 3 were evaluated through egg hatching. Asaricin 1 and isoasarone 2 showed potent ovicidal activity. Ovicidal activity for both compounds was up to 95% at 25μg/mL. Asaricin 1 and isoasarone 2 showed strong inhibition on acetylcholinesterase with relative IC50 values of 0.73 to 1.87 μg/mL respectively. These findings coupled with the high AChE inhibition may suggest that asaricin 1 and isoasarone 2 are neuron toxic compounds toward Aedes aegypti, Aedes albopictus and Culex quinquefasciatus. Further computational docking with Autodock Vina elaborates the possible interaction of asaricin 1 and isoasarone 2 with three possible binding sites of AChE which includes catalytic triads (CAS: S238, E367, H480), the peripheral sites (PAS: E72, W271) and anionic binding site (W83). The binding affinity of asaricin 1 and isoasarone 2 were relatively strong with asaricin 1 showed a higher binding affinity in the anionic pocket. PMID:27152416

  8. Inhibition and Larvicidal Activity of Phenylpropanoids from Piper sarmentosum on Acetylcholinesterase against Mosquito Vectors and Their Binding Mode of Interaction.

    Arshia Hematpoor

    Full Text Available Aedes aegypti, Aedes albopictus and Culex quinquefasciatus are vectors of dengue fever and West Nile virus diseases. This study was conducted to determine the toxicity, mechanism of action and the binding interaction of three active phenylpropanoids from Piper sarmentosum (Piperaceae toward late 3rd or early 4th larvae of above vectors. A bioassay guided-fractionation on the hexane extract from the roots of Piper sarmentosum led to the isolation and identification of three active phenylpropanoids; asaricin 1, isoasarone 2 and trans-asarone 3. The current study involved evaluation of the toxicity and acetylcholinesterase (AChE inhibition of these compounds against Aedes aegypti, Aedes albopictus and Culex quinquefasciatus larvae. Asaricin 1 and isoasarone 2 were highly potent against Aedes aegypti, Aedes albopictus and Culex quinquefasciatus larvae causing up to 100% mortality at ≤ 15 μg/mL concentration. The ovicidal activity of asaricin 1, isoasarone 2 and trans-asarone 3 were evaluated through egg hatching. Asaricin 1 and isoasarone 2 showed potent ovicidal activity. Ovicidal activity for both compounds was up to 95% at 25μg/mL. Asaricin 1 and isoasarone 2 showed strong inhibition on acetylcholinesterase with relative IC50 values of 0.73 to 1.87 μg/mL respectively. These findings coupled with the high AChE inhibition may suggest that asaricin 1 and isoasarone 2 are neuron toxic compounds toward Aedes aegypti, Aedes albopictus and Culex quinquefasciatus. Further computational docking with Autodock Vina elaborates the possible interaction of asaricin 1 and isoasarone 2 with three possible binding sites of AChE which includes catalytic triads (CAS: S238, E367, H480, the peripheral sites (PAS: E72, W271 and anionic binding site (W83. The binding affinity of asaricin 1 and isoasarone 2 were relatively strong with asaricin 1 showed a higher binding affinity in the anionic pocket.

  9. Antibacterial and biofilm inhibitory activities of bacteria associated with polychaetes

    Chellamnadar Vaikundavasagom Sunjaiy Shankar

    2015-06-01

    Full Text Available Objective: To study the antibacterial and antibiofilm activities expressed by epibiotic bacteria associated with the polychaetes Platynereis dumerilii and Syllis sp. Methods: A total of 32 cultivable bacterial strains were isolated from the two polychaete species. The crude extracts were tested for antibacterial activity and biofilm inhibitory activity against pathogenic and biofilm-forming bacterial strains. Extracts of the strains which showed strong activity were analyzed by thin-layer chromatography (TLC and the bacterial strains were identified based on 16S rRNA gene sequencing. Results: Extracts of 13 bacterial strains showed inhibitory activity against pathogenic and biofilm-forming bacteria. The crude extracts also affected the synthesis of extracellular polymeric substances and cell surface hydrophobicity of the Alteromonas sp. isolated from marine biofilm. The adhesion of Alteromonas sp. on glass surface showed significant variation between surface-associated bacterial crude extract treatment and control groups. Among the 13 bacteria, two strains PA8 and PA19 were further analyzed for bioactive fractions. Thinlayer chromatography indicated the presence of a single active fraction in the crude extract of both the bacterial strains. The epibiotic bacterial strains P8 and P19 were identified as Exiguobacterium sp. and Actinobacterium sp. respectively based on 16S rRNA gene sequencing. Conclusions: The present study indicates that bacteria associated with marine invertebrates inhabiting the coastal waters could be used as a potential source for the isolation of bioactive metabolites.

  10. Energetics of Ortho-7 (oxime drug translocation through the active-site gorge of tabun conjugated acetylcholinesterase.

    Vivek Sinha

    Full Text Available Oxime drugs translocate through the 20 Å active-site gorge of acetylcholinesterase in order to liberate the enzyme from organophosphorus compounds' (such as tabun conjugation. Here we report bidirectional steered molecular dynamics simulations of oxime drug (Ortho-7 translocation through the gorge of tabun intoxicated enzyme, in which time dependent external forces accelerate the translocation event. The simulations reveal the participation of drug-enzyme hydrogen bonding, hydrophobic interactions and water bridges between them. Employing nonequilibrium theorems that recovers the free energy from irreversible work done, we reconstruct potential of mean force along the translocation pathway such that the desired quantity represents an unperturbed system. The potential locates the binding sites and barriers for the drug to translocate inside the gorge. Configurational entropic contribution of the protein-drug binding entity and the role of solvent translational mobility in the binding energetics is further assessed.

  11. Production of the Acetylcholinesterase Inhibitor from Yarrowia lipolytica S-3

    Lee, Dae-Hyung; Lee, Ji-Su; Yi, Sung-Hun; Lee, Jong-Soo

    2008-01-01

    The acetylcholinesterase (AChE) inhibitor of Yarrowia lipolytica S-3 was maximally produced when it was incubated at 30℃ for 36 h in an optimal medium containing 1% yeast extract, 2% peptone and 2% glucose, with an initial pH 6.0. The final AChE inhibitory activity under these conditions was an IC50 value of 64 mg/ml. After partial purification of the AChE inhibitor by means of systematic solvent extraction, the final IC50 value of the partially purified AChE inhibitor was 0.75 mg/ml. We prep...

  12. Anti-Acetylcholinesterase Alkaloids from Annona glabra Leaf.

    Lee, Shoei-Sheng; Wu, Dong-Yi; Tsai, Sheng-Fa; Chen, Chien-Kuang

    2015-06-01

    Bioassay guided fractionation and separation of the EtOH extract of Annona glabra leaf against acetylcholinesterse led to the characterization of 15 alkaloids. Among them, (-)-actinodaphnine (2) and (-)-(6aS,7R)-7-hydroxyactinodaphnine (9) are new aporphines, although (+)-2 and (±)-2 have been found in several plants. Their structures were established by spectroscopic analysis. (-)-Anolobine (5) and (-)-roemeroline (8) showed moderate inhibitory activity against eel acetylcholinesterase with IC50 values of 22.4 and 26.3 μM, respectively. PMID:26197510

  13. Possibility of Acetylcholinesterase Overexpression in Alzheimer Disease Patients after Therapy with Acetylcholinesterase Inhibitors

    Alžběta Kračmarová; Lucie Drtinová; Miroslav Pohanka

    2015-01-01

    Acetylcholinesterase is an enzyme responsible for termination of excitatory transmission at cholinergic synapses by the hydrolyzing of a neurotransmitter acetylcholine. Nowadays, other functions of acetylcholinesterase in the organism are considered, for example its role in regulation of apoptosis. Cholinergic nervous system as well as acetylcholinesterase activity is closely related to pathogenesis of Alzheimer disease. The mostly used therapy of Alzheimer disease is based on enhancing choli...

  14. Kinetics of Acetylcholinesterase Inhibition by an Aqueous Extract of Mentha longifolia Leaves

    Chandra Shekhar; Suresh Kumar

    2014-01-01

    Cholinesterase inhibitors are the class of compounds which inhibit cholinesterase enzyme. These are used as drugs for symptomatic treatment of Alzheimer’s disease (AD). The present study, evaluate anti-cholinesterase property of an aqueous extract of Mentha longifolia leaves, which is an aromatic plant traditionally used for several medicinal properties. Ellman’s method was used to determine the acetylcholinesterase (AChE) enzyme inhibitory activity of an aqueous extracts of Mentha longifolia...

  15. In vitro acetylcholinesterase inhibition by psoralen using molecular docking and enzymatic studies

    Gauresh Somani; Chinmay Kulkarni; Prashant Shinde; Rupesh Shelke; Kirti Laddha; Sadhana Sathaye

    2015-01-01

    Introduction: Alzheimer′s disease (AD) has increased at an alarming rate and is now a worldwide health problem. Inhibitors of acetylcholinesterase (AChE) leading to inhibition of acetylcholine breakdown constitute the main therapeutic strategy for AD. Psoralen was investigated as inhibitor of AChE enzyme in an attempt to explore its potential for the management of AD. Materials and Methods: Psoralen was isolated from powdered Psoralea corylifolia fruits. AChE enzyme inhibitory activity of dif...

  16. Acetylcholinesterase immobilization and characterization, and comparison of the activity of the porous silicon-immobilized enzyme with its free counterpart.

    Saleem, Muhammad; Rafiq, Muhammad; Seo, Sung-Yum; Lee, Ki Hwan

    2016-01-01

    A successful prescription is presented for acetylcholinesterase physically adsorbed on to a mesoporous silicon surface, with a promising hydrolytic response towards acetylthiocholine iodide. The catalytic behaviour of the immobilized enzyme was assessed by spectrophotometric bioassay using neostigmine methyl sulfate as a standard acetycholinesterase inhibitor. The surface modification was studied through field emission SEM, Fourier transform IR spectroscopy, energy-dispersive X-ray spectroscopy, cathode luminescence and X-ray photoelectron spectroscopy analysis, photoluminescence measurement and spectrophotometric bioassay. The porous silicon-immobilized enzyme not only yielded greater enzyme stability, but also significantly improved the native photoluminescence at room temperature of the bare porous silicon architecture. The results indicated the promising catalytic behaviour of immobilized enzyme compared with that of its free counterpart, with a greater stability, and that it aided reusability and easy separation from the reaction mixture. The porous silicon-immobilized enzyme was found to retain 50% of its activity, promising thermal stability up to 90°C, reusability for up to three cycles, pH stability over a broad pH of 4-9 and a shelf-life of 44 days, with an optimal hydrolytic response towards acetylthiocholine iodide at variable drug concentrations. On the basis of these findings, it was believed that the porous silicon-immobilized enzyme could be exploited as a reusable biocatalyst and for screening of acetylcholinesterase inhibitors from crude plant extracts and synthesized organic compounds. Moreover, the immobilized enzyme could offer a great deal as a viable biocatalyst in bioprocessing for the chemical and pharmaceutical industries, and bioremediation to enhance productivity and robustness. PMID:26839417

  17. Acetylcholinesterase immobilization and characterization, and comparison of the activity of the porous silicon-immobilized enzyme with its free counterpart

    Saleem, Muhammad; Rafiq, Muhammad; Seo, Sung-Yum; Lee, Ki Hwan

    2016-01-01

    A successful prescription is presented for acetylcholinesterase physically adsorbed on to a mesoporous silicon surface, with a promising hydrolytic response towards acetylthiocholine iodide. The catalytic behaviour of the immobilized enzyme was assessed by spectrophotometric bioassay using neostigmine methyl sulfate as a standard acetycholinesterase inhibitor. The surface modification was studied through field emission SEM, Fourier transform IR spectroscopy, energy-dispersive X-ray spectroscopy, cathode luminescence and X-ray photoelectron spectroscopy analysis, photoluminescence measurement and spectrophotometric bioassay. The porous silicon-immobilized enzyme not only yielded greater enzyme stability, but also significantly improved the native photoluminescence at room temperature of the bare porous silicon architecture. The results indicated the promising catalytic behaviour of immobilized enzyme compared with that of its free counterpart, with a greater stability, and that it aided reusability and easy separation from the reaction mixture. The porous silicon-immobilized enzyme was found to retain 50% of its activity, promising thermal stability up to 90°C, reusability for up to three cycles, pH stability over a broad pH of 4–9 and a shelf-life of 44 days, with an optimal hydrolytic response towards acetylthiocholine iodide at variable drug concentrations. On the basis of these findings, it was believed that the porous silicon-immobilized enzyme could be exploited as a reusable biocatalyst and for screening of acetylcholinesterase inhibitors from crude plant extracts and synthesized organic compounds. Moreover, the immobilized enzyme could offer a great deal as a viable biocatalyst in bioprocessing for the chemical and pharmaceutical industries, and bioremediation to enhance productivity and robustness. PMID:26839417

  18. Trypsin inhibitory activity of artemisinin and its biotransformed product

    Summary: Artemisinin (1 ), a sesquiterpene lactone is an important constituent of anti-malarial drugs. In the present study, it was extracted from aerial parts of Artemisia roxburghiana Besser. Biotransformation of artemisinin ( 1 ) was carried out in the culture of Aspergillus niger GC-4 which yielded 5-hydroxy artemisinin (2 ) The structures of 1-2 were confirmed through spectral studies. Both compounds were screened against trypsin using colorimetric method. The biotransformed product 2 showed significant protease inhibitory activity with 53.5 +- 1.6% inhibition and IC/sub 50/ = 0.29 +- 0.02 mM as compared to artemisinin (20.4 +- 0.3% inhibition). (author)

  19. Inhibitory Effects of Resveratrol Analogs on Mushroom Tyrosinase Activity

    Nádia Rezende Barbosa Raposo

    2012-10-01

    Full Text Available Skin pigmentation disorders typically involve an overproduction or uneven distribution of melanin, which results in skin spots. Resveratrol can inhibit tyrosinase, the active enzyme in the synthesis of melanin, but it does not inhibit the synthesis of melanin to an extent that enables its use alone as a skin whitening agent in pharmaceutical formulations, so its use as a coadjuvant in treatment of hyperpigmentation is suggested. Six resveratrol analogs were tested for tyrosinase inhibitory activity in vitro. Among the analogs tested, compound D was the most powerful tyrosinase inhibitor (IC50 = 28.66 µg/mL, two times more active than resveratrol (IC50 = 57.05 µg/mL, followed by the analogs A, E, B, F and C, respectively. This demonstrated that the hydroxylation at C4' on the phenolic ring was the molecular modification with most importance for the observed activity.

  20. Synthesis and biological activity of 3,6-diaryl-7H-thiazolo[3,2-b][1,2,4]triazin-7-one derivatives as novel acetylcholinesterase inhibitors

    WAN; David; ChiCheong

    2010-01-01

    Acetylcholinesterase inhibitors played significant roles in treatment of Alzheimer’s disease.Based on the research foundation of our previous work and molecular modeling,twelve 3,6-diaryl-7H-thiazolo[3,2-b][1,2,4]triazin-7-one derivatives were synthesized and characterized by mass spectra,infrared spectra,NMR and elemental analyses.The study of AChE inhibitory activity was carried out using the Ellman colorimetric assay with huperzine-A as the positive control.All target compounds exhibited more than 40% inhibition at 10 μM.Some target compounds showed good inhibition against AChE.The preliminary structure-activity relationships were the halogen atoms at the phenyl ring at the C6 position,the hydroxy groups and the long side chains at the phenyl ring at the C3 position of the parent nucleus played significant roles in the AChE inhibitory activity of the target compounds.

  1. Design, Synthesis and Inhibitory Activity of Photoswitchable RET Kinase Inhibitors

    Ferreira, Rubén; Nilsson, Jesper R.; Solano, Carlos; Andréasson, Joakim; Grøtli, Morten

    2015-05-01

    REarranged during Transfection (RET) is a transmembrane receptor tyrosine kinase required for normal development and maintenance of neurons of the central and peripheral nervous systems. Deregulation of RET and hyperactivity of the RET kinase is intimately connected to several types of human cancers, most notably thyroid cancers, making it an attractive therapeutic target for small-molecule kinase inhibitors. Novel approaches, allowing external control of the activity of RET, would be key additions to the signal transduction toolbox. In this work, photoswitchable RET kinase inhibitors based on azo-functionalized pyrazolopyrimidines were developed, enabling photonic control of RET activity. The most promising compound displays excellent switching properties and stability with good inhibitory effect towards RET in cell-free as well as live-cell assays and a significant difference in inhibitory activity between its two photoisomeric forms. As the first reported photoswitchable small-molecule kinase inhibitor, we consider the herein presented effector to be a significant step forward in the development of tools for kinase signal transduction studies with spatiotemporal control over inhibitor concentration in situ.

  2. Aqueous Extracts from Tunisian Diplotaxis: Phenol Content, Antioxidant and Anti-Acetylcholinesterase Activities, and Impact of Exposure to Simulated Gastrointestinal Fluids

    Nada Bahloul

    2016-04-01

    Full Text Available Antioxidants have been considered essential for preventing cell damage by scavenging deleterious free radicals. The consumption of antioxidant-rich plants is associated with a reduced risk of some chronic diseases. This study evaluates the antioxidant and acetylcholinesterase inhibition activities of aqueous extracts obtained from different parts of Diplotaxis simplex and Diplotaxis harra from Tunisia. The study also aimed to investigate the action of simulated gastrointestinal juice on antioxidant activities of both extracts. The total phenolic, flavone and flavonol, and flavanone and dihydroflavonol contents were determined by Folin–Ciocalteau, aluminum chloride and 2,4-dinitrophenylhydrazine colorimetric methods, respectively. The metal ion chelating activity, acetylcholinesterase inhibition capacity, and free radical scavenging potential of the extracts towards ABTS (2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid, DPPH (2,2-diphenyl-1-picrylhydrazyl, hydroxyl, superoxide and nitric oxide were also evaluated. The action of simulated gastro-intestinal fluids on the flavone and flavonol content and total antioxidant activity of the flower extracts was surveyed. Extracts from the seeds and flowers of D. simplex and D. harra displayed the highest amounts of phenols (2691.7 and 2694.5 mg Caffeic Acid Equivalent (CAE/100 mg; 3433.4 and 2647.2 mg CAE/100 mg, respectively and flavonols/flavones (2144.4 and 2061.1 mg Rutin Equivalent (RE/100 g; 1922.6 and 1461.1 mg RE/100 g, respectively. The flower and seed extracts exhibited the highest rates of antioxidant and acetylcholinesterase inhibition activities. A decrease in the flavonoid content and antioxidant activity was observed after extract exposure to simulated saliva. Antioxidant and acetylcholinesterase inhibition activities were noted to depend on plant species and plant parts. In vitro gastrointestinal digestion is useful in assessing the bio-accessibility of compounds with

  3. Aqueous Extracts from Tunisian Diplotaxis: Phenol Content, Antioxidant and Anti-Acetylcholinesterase Activities, and Impact of Exposure to Simulated Gastrointestinal Fluids.

    Bahloul, Nada; Bellili, Sana; Aazza, Smail; Chérif, Ameur; Faleiro, Maria Leonor; Antunes, Maria Dulce; Miguel, Maria Graça; Mnif, Wissem

    2016-01-01

    Antioxidants have been considered essential for preventing cell damage by scavenging deleterious free radicals. The consumption of antioxidant-rich plants is associated with a reduced risk of some chronic diseases. This study evaluates the antioxidant and acetylcholinesterase inhibition activities of aqueous extracts obtained from different parts of Diplotaxis simplex and Diplotaxis harra from Tunisia. The study also aimed to investigate the action of simulated gastrointestinal juice on antioxidant activities of both extracts. The total phenolic, flavone and flavonol, and flavanone and dihydroflavonol contents were determined by Folin-Ciocalteau, aluminum chloride and 2,4-dinitrophenylhydrazine colorimetric methods, respectively. The metal ion chelating activity, acetylcholinesterase inhibition capacity, and free radical scavenging potential of the extracts towards ABTS (2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid), DPPH (2,2-diphenyl-1-picrylhydrazyl), hydroxyl, superoxide and nitric oxide were also evaluated. The action of simulated gastro-intestinal fluids on the flavone and flavonol content and total antioxidant activity of the flower extracts was surveyed. Extracts from the seeds and flowers of D. simplex and D. harra displayed the highest amounts of phenols (2691.7 and 2694.5 mg Caffeic Acid Equivalent (CAE)/100 mg; 3433.4 and 2647.2 mg CAE/100 mg, respectively) and flavonols/flavones (2144.4 and 2061.1 mg Rutin Equivalent (RE)/100 g; 1922.6 and 1461.1 mg RE/100 g, respectively). The flower and seed extracts exhibited the highest rates of antioxidant and acetylcholinesterase inhibition activities. A decrease in the flavonoid content and antioxidant activity was observed after extract exposure to simulated saliva. Antioxidant and acetylcholinesterase inhibition activities were noted to depend on plant species and plant parts. In vitro gastrointestinal digestion is useful in assessing the bio-accessibility of compounds with biological activities from

  4. Origin of aromatase inhibitory activity via proteochemometric modeling.

    Simeon, Saw; Spjuth, Ola; Lapins, Maris; Nabu, Sunanta; Anuwongcharoen, Nuttapat; Prachayasittikul, Virapong; Wikberg, Jarl E S; Nantasenamat, Chanin

    2016-01-01

    Aromatase, the rate-limiting enzyme that catalyzes the conversion of androgen to estrogen, plays an essential role in the development of estrogen-dependent breast cancer. Side effects due to aromatase inhibitors (AIs) necessitate the pursuit of novel inhibitor candidates with high selectivity, lower toxicity and increased potency. Designing a novel therapeutic agent against aromatase could be achieved computationally by means of ligand-based and structure-based methods. For over a decade, we have utilized both approaches to design potential AIs for which quantitative structure-activity relationships and molecular docking were used to explore inhibitory mechanisms of AIs towards aromatase. However, such approaches do not consider the effects that aromatase variants have on different AIs. In this study, proteochemometrics modeling was applied to analyze the interaction space between AIs and aromatase variants as a function of their substructural and amino acid features. Good predictive performance was achieved, as rigorously verified by 10-fold cross-validation, external validation, leave-one-compound-out cross-validation, leave-one-protein-out cross-validation and Y-scrambling tests. The investigations presented herein provide important insights into the mechanisms of aromatase inhibitory activity that could aid in the design of novel potent AIs as breast cancer therapeutic agents. PMID:27190705

  5. Inhibitory activity of xanthine oxidase by fractions Crateva adansonii

    Abdullahi A; Kolo MZ; Hamzah RU; Jigam AA; Yahya A; Kabiru AY; Muhammad H; Sakpe S; Adefolalu FS; Isah MC

    2012-01-01

    Objective: To study the inhibitory effect of various extracts from Crateva adansonii (C. adansonii) used traditionally against several inflammatory diseases such as rheumatism, arthritis, and gout, was investigated on purified bovine milk xanthine oxidase (XO) activity. Methods:Xanthine oxidase inhibitory activity was assayed spectrophotometrically and the degree of enzyme inhibition was determined by measuring the increase in absorbance at 295 nm associated with uric acid formation. Enzyme kinetics was carried out using Lineweaver-Burk plots using xanthine as the substrate. Results: Among the fractions tested, the chloroform fraction exhibited highest potency (IC50 20.2±1.6 μg/mL) followed by the petroleum ether (IC50 30.1±2.2 μg/mL), ethyl acetate (IC50 43.9±1.4 μg/mL) and residual (IC50 98.0±3.3 μg/mL) fractions. The IC50 value of allopurinol used, as the standard was 5.7±0.3 μg/mL. Conclusions: Enzyme inhibition mechanism indicated that the mode of inhibition was of a mixed type. Our findings suggest that the therapeutic use of these plants may be due to the observed Xanthine oxidase inhibition, thereby supporting their use in traditional folk medicine against inflammatory-related diseases, in particular, gout.

  6. Acute effects of chlorpyryphos-ethyl and secondary treated effluents on acetylcholinesterase and butyrylcholinesterase activities in Carcinus maenas

    Jihene Ghedira; Jamel Jebali; Zied Bouraoui; Mohamed Banni; Lassaad Chouba; Hamadi Boussetta

    2009-01-01

    The acute effects of commercial formulation of chlorpyrifos-ethyl (Dursban(r)) and the secondary treated industrial/urban effluent (STIUE) exposure on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities in hepatopancreas and gills of Mediterranean crab Carcinus maenas were investigated. After 2 d of exposure to chlorpyriphos-ethyl, the AChE activity was inhibited in both organs at concentrations of 3.12 and 7.82 μg/L, whereas the BuChE was inhibited only at higher concentration 7.82 μg/L of commercial preparation Dursban(r). The exposure of crabs to Dursban(r) (3.12 μg/L) showed a significant decrement of AChE activity at 24 and 48 h, whereas the BuChE was inhibited only after 24 h and no inhibition for both enzymes was observed after 72 h. Moreover, a significant repression of AChE activity was observed in both organs of C. maenas exposed to 5% of STIUE. Our experiments indicated that the measurement of AChE activity in gills and hepatopancreas of C. meanas would be useful biomarker of organophosphorous (OP) and of neurotoxic effects of STIUE in Tunisia.

  7. Highly sensitive electrochemiluminescenc assay of acetylcholinesterase activity based on dual biomarkers using Pd-Au nanowires as immobilization platform.

    Ye, Cui; Wang, Min-Qiang; Zhong, Xia; Chen, Shihong; Chai, Yaqin; Yuan, Ruo

    2016-05-15

    One-dimensional Pd-Au nanowires (Pd-Au NWs) were prepared and applied to fabricate an electrochemiluminescence (ECL) biosensor for the detection of acetylcholinesterase (AChE) activity. Compared with single-component of Pd or Au, the bimetallic nanocomposite of Pd-Au NWs offers a larger surface area for the immobilization of enzyme, and displays superior electrocatalytic activity and efficient electron transport capacity. In the presence of AChE and choline oxidase (ChOx), acetylcholine (ATCl) is hydrolyzed by AChE to generate thiocholine, then thiocholine is catalyzed by ChOx to produce H2O2 in situ, which serves as the coreactant to effectively enhance the ECL intensity in luminol-ECL system. The detection principle is based on the inhibited AChE and reactivated AChE as dual biomarkers, in which AChE was inhibited by organophosphorus (OP) agents, and then reactivated by obidoxime. Such dual biomarkers method can achieve credible evaluation for AChE activity via providing AChE activity before and after reactivation. The liner range for AChE activity detection was from 0.025 U L(-1) to 25 KU L(-1) with a low detection limit down to 0.0083 U L(-1). PMID:26686921

  8. Acetylcholinesterase immobilization and characterization, and comparison of the activity of the porous silicon-immobilized enzyme with its free counterpart

    Saleem, Muhammad; Rafiq, Muhammad; Seo, Sung-Yum; Lee, Ki Hwan

    2016-01-01

    The physically adsorbed acetylcholinesterase on mesoporous silicon surface is presented. The catalytic behavior of immobilized enzyme was assessed by spectrophotometric bioassay. The immobilization enhanced the reusability, shelf life and thermal as well as pH stability

  9. 5,6-Dimethoxybenzofuran-3-one Derivatives: a Novel Series of Dual Acetylcholinesterase/Butyrylcholinesterase Inhibitors Bearing Benzyl Pyridinium Moiety

    Mohammad Abdollahi

    2013-02-01

    Full Text Available Several studies have been focused on design and synthesis of multi-target anti Alzheimer compounds. Utilizing of the dual Acetylcholinesterase/Butyrylcholinesterase inhibitors has gained more interest to treat the Alzheimer’s disease. As a part of a research program to find a novel drug for treating Alzheimer disease, we have previously reported 6-alkoxybenzofuranone derivatives as potent acetylcholinesterase inhibitors. In continuation of our work, we would like to report the synthesis of 5,6-dimethoxy benzofuranone derivatives bearing a benzyl pyridinium moiety as dual Acetylcholinesterase/Butyrylcholinesterase inhibitors.MethodsThe synthesis of target compounds was carried out using a conventional method. Bayer-Villiger oxidation of 3,4-dimethoxybenzaldehyde furnished 3,4-dimethoxyphenol. The reaction of 3,4-dimethoxyphenol with chloroacetonitrile followed by treatment with HCl solution and then ring closure yielded the 5,6-dimethoxy benzofuranone. Condensation of the later compound with pyridine-4-carboxaldehyde and subsequent reaction with different benzyl halides afforded target compounds. The biological activity was measured using standard Ellman’s method. Docking studies were performed to get better insight into interaction of compounds with receptor.ResultsThe in vitro anti acetylcholinesterase/butyrylcholinesterase activity of compounds revealed that, all of the target compounds have good inhibitory activity against both Acetylcholinesterase/Butyrylcholinesterase enzymes in which compound 5b (IC50 = 52 ± 6.38nM was the most active compound against acetylcholinesterase. The same binding mode and interactions were observed for the reference drug donepezil and compound 5b in docking study.ConclusionsIn this study, we presented a new series of benzofuranone-based derivatives having pyridinium moiety as potent dual acting Acetylcholinesterase/Butyrylcholinesterase inhibitors.

  10. Detection of Carbofuran with Immobilized Acetylcholinesterase Based on Carbon Nanotubes-Chitosan Modified Electrode

    Shuping Zhang

    2013-01-01

    Full Text Available A sensitive and stable enzyme biosensor based on efficient immobilization of acetylcholinesterase (AChE to MWNTs-modified glassy carbon electrode (GCE with chitosan (CS by layer-by-layer (LBL technique for rapid determination of carbofuran has been devised. According to the inhibitory effect of carbamate pesticide on the enzymatic activity of AChE, we use carbofuran as a model pesticide. The inhibitory effect of carbofuran on the biosensor was proportional to concentration of carbofuran in the range from  g/L to  g/L with a detection limit of  g/L. This biosensor is a promising new method for pesticide analysis.

  11. Active compounds from a diverse library of triazolothiadiazole and triazolothiadiazine scaffolds: synthesis, crystal structure determination, cytotoxicity, cholinesterase inhibitory activity, and binding mode analysis.

    Khan, Imtiaz; Ibrar, Aliya; Zaib, Sumera; Ahmad, Sarfraz; Furtmann, Norbert; Hameed, Shahid; Simpson, Jim; Bajorath, Jürgen; Iqbal, Jamshed

    2014-11-01

    In an effort to identify novel cholinesterase candidates for the treatment of Alzheimer's disease (AD), a diverse array of potentially bioactive compounds including triazolothiadiazoles (4a-h and 5a-f) and triazolothiadiazines (6a-h) was obtained in good yields through the cyclocondensation reaction of 4-amino-5-(pyridin-3-yl)-4H-1,2,4-triazole-3-thiol (3) with various substituted aryl/heteroaryl/aryloxy acids and phenacyl bromides, respectively. The structures of newly prepared compounds were confirmed by IR, (1)H and (13)C NMR spectroscopy and, in case of 4a, by single crystal X-ray diffraction analysis. The purity of the synthesized compounds was ascertained by elemental analysis. The newly synthesized conjugated heterocycles were screened for cholinesterase inhibitory activity against electric eel acetylcholinesterase (EeAChE) and horse serum butyrylcholinesterase (hBChE). Among the evaluated hybrids, several compounds were identified as potent inhibitors. Compounds 5b and 5d were most active with an IC50 value of 3.09 ± 0.154 and 11.3 ± 0.267 μM, respectively, against acetylcholinesterase, whereas 5b, 6a and 6g were most potent against butyrylcholinesterase, with an IC50 of 0.585 ± 0.154, 0.781 ± 0.213, and 1.09 ± 0.156 μM, respectively, compared to neostigmine and donepezil as standard drugs. The synthesized heteroaromatic compounds were also tested for their cytotoxic potential against lung carcinoma (H157) and vero cell lines. Among them, compound 6h exhibited highest antiproliferative activity against H157 cell lines, with IC50 value of 0.96 ± 0.43 μM at 1mM concentration as compared to vincristine (IC50=1.03 ± 0.04 μM), standard drug used in this study. PMID:25257911

  12. Interaction of lobed kudzuvine root, rhizoma chuanxiong with both acetylcholinesterase and beta-amyloid (Aβ1-42

    Li Shuai

    2013-01-01

    Full Text Available Background: Lobed kudzuvine root and rhizoma chuanxiong are effective drugs in traditional Chinese medicine. Objective: Extracts of the two medicines were investigated for their in vitro of beta-amyloid (Aβ1-42-aggregation-and acetylcholinesterase (AChE-inhibitory activities. Materials and Methods: The interaction of lobed kudzuvine root, rhizoma chuanxiong with both acetylcholinesterase and beta-amyloid (Aβ1-42 were studied by Michaelis-Menten equations, Thioflavin T (ThT fluorescence analysis and transmission electron microscope (TEM. Results: Inhibition of acetylcholinesterase showed that 1-butanol fraction of the two medicines were noncompetitive inhibition, apparent inhibition constants were 9.947 and 7.1523. ThT fluorescence analysis and TEM results indicated that inhibition of the water fraction and 1-butanol fraction (both lobed kudzuvine root and rhizoma chuanxiong was better. Conclusion: The result supported further research on chemical constituents and pharmacological mechanisms.

  13. Aqueous Extracts from Tunisian Diplotaxis: Phenol Content, Antioxidant and Anti-Acetylcholinesterase Activities, and Impact of Exposure to Simulated Gastrointestinal Fluids

    Nada Bahloul; Sana Bellili; Smail Aazza; Ameur Chérif; Maria Leonor Faleiro; Maria Dulce Antunes; Maria Graça Miguel; Wissem Mnif

    2016-01-01

    Antioxidants have been considered essential for preventing cell damage by scavenging deleterious free radicals. The consumption of antioxidant-rich plants is associated with a reduced risk of some chronic diseases. This study evaluates the antioxidant and acetylcholinesterase inhibition activities of aqueous extracts obtained from different parts of Diplotaxis simplex and Diplotaxis harra from Tunisia. The study also aimed to investigate the action of simulated gastrointestinal juice on antio...

  14. Report: screening of selected medicinal plants for their enzyme inhibitory potential - a validation of their ethnopharmacological uses.

    Khuda, Fazli; Iqbal, Zafar; Khan, Ayub; Zakiullah; Shah, Yasar; Khan, Abad

    2014-05-01

    In present study four medicinal plants namely Valeriana wallichii, Xanthium strumarium, Achyranthes aspera and Duchesnea indica belonging to different families were collected in Khyber Pakhtunkhwa province and crude extract and subsequent fractions were analyzed for their inhibitory potential against acetylcholinesterase, butyrylcholinesterase and α-glucosidase enzymes. Valeriana wallichii, Xanthium strumarium and Achyranthes aspera were significantly active against cholinesterases. Chloroform and ethylacetate fractions of Valeriana wallichii exhibited significant activity against acetylcholinesterase (IC50: 61μg/ml) and butyrylcholinesterase enzymes (IC50: 58μg/ml), respectively. Similarly ethylacetate fraction of Achyranthes aspera showed significant activity against acetylcholinesterase (IC50: 61 μg/ml) and butyrylcholinesterase enzymes (IC50: 61 μg/ml), respectively. In case of α-glucosidase enzyme, the chloroform fraction of Xanthium strumarium exhibited significant inhibitory activity (IC50: 72 μg/ml) as compared to the standard compound acarbose (IC50: 483 μg/ml). Duchesnea indica showed no such activities. PMID:24811822

  15. Inhibitory neurotransmission regulates vagal efferent activity and gastric motility.

    McMenamin, Caitlin A; Travagli, R Alberto; Browning, Kirsteen N

    2016-06-01

    The gastrointestinal tract receives extrinsic innervation from both the sympathetic and parasympathetic nervous systems, which regulate and modulate the function of the intrinsic (enteric) nervous system. The stomach and upper gastrointestinal tract in particular are heavily influenced by the parasympathetic nervous system, supplied by the vagus nerve, and disruption of vagal sensory or motor functions results in disorganized motility patterns, disrupted receptive relaxation and accommodation, and delayed gastric emptying, amongst others. Studies from several laboratories have shown that the activity of vagal efferent motoneurons innervating the upper GI tract is inhibited tonically by GABAergic synaptic inputs from the adjacent nucleus tractus solitarius. Disruption of this influential central GABA input impacts vagal efferent output, hence gastric functions, significantly. The purpose of this review is to describe the development, physiology, and pathophysiology of this functionally dominant inhibitory synapse and its role in regulating vagally determined gastric functions. PMID:27302177

  16. Cerebrospinal fluid (CSF 25-hydroxyvitamin D concentration and CSF acetylcholinesterase activity are reduced in patients with Alzheimer's disease.

    Per Johansson

    Full Text Available BACKGROUND: Little is known of vitamin D concentration in cerebrospinal fluid (CSF in Alzheimer's disease (AD and its relation with CSF acetylcholinesterase (AChE activity, a marker of cholinergic function. METHODS: A cross-sectional study of 52 consecutive patients under primary evaluation of cognitive impairment and 17 healthy controls. The patients had AD dementia or mild cognitive impairment (MCI diagnosed with AD dementia upon follow-up (n = 28, other dementias (n = 12, and stable MCI (SMCI, n = 12. We determined serum and CSF concentrations of calcium, parathyroid hormone (PTH, 25-hydroxyvitamin D (25OHD, and CSF activities of AChE and butyrylcholinesterase (BuChE. FINDINGS: CSF 25OHD level was reduced in AD patients (P < 0.05, and CSF AChE activity was decreased both in patients with AD (P < 0.05 and other dementias (P < 0.01 compared to healthy controls. None of the measured variables differed between BuChE K-variant genotypes whereas the participants that were homozygous in terms of the apolipoprotein E (APOE ε4 allele had decreased CSF AChE activity compared to subjects lacking the APOE ε4 allele (P = 0.01. In AD patients (n=28, CSF AChE activity correlated positively with CSF levels of total tau (T-tau (r = 0.44, P < 0.05 and phosphorylated tau protein (P-tau (r = 0.50, P < 0.01, but CSF activities of AChE or BuChE did not correlate with serum or CSF levels of 25OHD. CONCLUSIONS: In this pilot study, both CSF 25OHD level and CSF AChE activity were reduced in AD patients. However, the lack of correlations between 25OHD levels and CSF activities of AChE or BuChE might suggest different mechanisms of action, which could have implications for treatment trials.

  17. Microbial and xanthine dehydrogenase inhibitory activity of some flavones.

    Khobragade, C N; Bodade, Ragini G; Shinde, M S; Jaju, Deepa R; Bhosle, R B; Dawane, B S

    2008-06-01

    Xanthine dehydrogenase (XDH) is responsible for the pathological condition called Gout. In the present study different flavones synthesized from chalcone were evaluated in vitro for their inhibitory activity. Inhibitory activity of flavones on XDH was determined in terms of inhibition of uric acid synthesis from Xanthine. The enzymatic activity was found maximum at pH 7.5 and temperature 40 degrees C. The flavones 6-chloro-2-[3-(4-hydroxy-phenyl)-1-phenyl-1-H-pyrazol-4-yl]-chromen-4-one (F(1)) and 6-chloro-7methyl-2-[3-(4-chloro-phenyl)-1-phenyl-1-H-pyrazol-4-yl]-chromen-4-one(F(2)),were noncompetitive and competitive inhibitor with Ki values 1.1 and 0.22 respectively. The flavones (F(1)), (F(2)), 6-chloro-2-[3-(4-chloro-phenyl)-1phenyl-1-H-pyrazol-4-yl]-chromen-4-one(F(3)), 8-bromo-6-chloro-2-[3-(4-chloro-phenyl)-1-phenyl-1-H-pyrazol-4-yl]-chromen-4-one (F(4)), 2-[3-(4-hydroxy-phenyl)-1-phenyl-1-H-pyrazol-4-yl]-chromen-4-one (F(5)) and 6-methyl-2-[3-(4-hydroxy-phenyl)-1-phenyl-1-H-pyrazol-4-yl]-chromen-4-one (F(6)) were also screened for their antimicrobial activity, measured in terms of zone of inhibition. A broad spectrum antifungal activity was obtained against Trichoderma viridae, Candida albicans, Microsporum cannis, Penicillium chrysogenum and Fusarium moniliformae. In case of Aspergillus niger and Aspergillus flavous only spore formation was affected, while antibacterial activity was observed against Staphylococcus aureus, Bacillus subtilis and Serratia marsecens only. The flavones were further analyzed for quantitative structural activity relationship study (QSAR) by using PASS, online software to determine their Pa value. Toxicity and drug relevant properties were revealed by PALLAS software in terms of their molecular weight. Log P values were also studied. The result showed both the F(1) and F(2) flavones as antigout and therefore supports the development of novel drugs for the treatment of gout. PMID:18569337

  18. Neurotoxic effects of nickel chloride in the rainbow trout brain: Assessment of c-Fos activity, antioxidant responses, acetylcholinesterase activity, and histopathological changes.

    Topal, Ahmet; Atamanalp, Muhammed; Oruç, Ertan; Halıcı, Mesut Bünyami; Şişecioğlu, Melda; Erol, Hüseyin Serkan; Gergit, Arzu; Yılmaz, Bahar

    2015-06-01

    The aim of this study was to determine the biochemical, immunohistochemical, and histopathological effects of nickel chloride (Ni) in the rainbow trout brain. Fish were exposed to Ni concentrations (1 mg/L and 2 mg/L) for 21 days. At the end of the experimental period, brain tissues were taken from all fish for c-Fos activity and histopathological examination and determination of acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT) enzyme activities, lipid peroxidation (LPO), and glutathione (GSH) levels. Our results showed that Ni treatment caused a significant increase in the brain SOD activity and in LPO and GSH levels (p enzyme activities (p cells. Brain tissues were characterized by demyelination and necrotic changes. These results suggested that Ni treatment causes oxidative stress, changes in c-Fos activity, and histopathological damage in the fish brain. PMID:25666867

  19. Acetylcholinesterase activity in the terrestrial snail Xeropicta derbentina transplanted in apple orchards with different pesticide management strategies

    Apple orchards are highly manipulated crops in which large amounts of pesticides are used. Some of these pesticides lack target specificity and can cause adverse effects in non-target organisms. In order to evaluate the environmental risk of these products, the use of transplanted sentinel organisms avoids side-effects from past events and facilitate comparison of multiple sites in a short time. We released specimens of the terrestrial snail Xeropicta derbentina in each 5 of two kinds of apple orchards with either conventional or organic management strategies plus in a single abandoned orchard. After one month, individuals were retrieved in order to measure acetylcholinesterase (AChE) activity. Mean values of AChE activity were significantly reduced in all conventional apple orchards compared to the others. Results show that the measurement of biomarkers such as AChE inhibition in transplated X. derbentina could be useful in the environmental risk assessment of post-authorized pesticides. - Snails as sentinel species to evaluate insecticide impacts in apple orchards.

  20. Acetylcholinesterase activity in the terrestrial snail Xeropicta derbentina transplanted in apple orchards with different pesticide management strategies

    Mazzia, Christophe, E-mail: christophe.mazzia@univ-avignon.f [Universite d' Avignon et des Pays de Vaucluse, Laboratoire de Toxicologie Environnementale, UMR 406 UAPV/INRA, ' Abeilles et Environnement' , Domaine St Paul, Site Agroparc, 84914 Avignon Cedex 9 France (France); Capowiez, Yvan [INRA, UR 1115 ' Plante et Systemes Horticoles' , Domaine St Paul, Site Agroparc, 84914 Avignon Cedex 9 France (France); Sanchez-Hernandez, Juan C. [Laboratory of Ecotoxicology, Faculty of Environmental Science, University of Castilla-La Mancha, Avda. Carlos III s/n, 45071 Toledo (Spain); Koehler, Heinz-R. [Animal Physiological Ecology, Institute for Evolution and Ecology, University of Tuebingen, Konrad-Adenauer-Str. 20, D-72072 Tuebingen (Germany); Triebskorn, Rita [Animal Physiological Ecology, Institute for Evolution and Ecology, University of Tuebingen, Konrad-Adenauer-Str. 20, D-72072 Tuebingen (Germany); Steinbeis-Transfer Center for Ecotoxicology and Ecophysiology, Blumenstrasse 13, D-72108 Rottenburg (Germany); Rault, Magali [Universite d' Avignon et des Pays de Vaucluse, Laboratoire de Toxicologie Environnementale, UMR 406 UAPV/INRA, ' Abeilles et Environnement' , Domaine St Paul, Site Agroparc, 84914 Avignon Cedex 9 France (France)

    2011-01-15

    Apple orchards are highly manipulated crops in which large amounts of pesticides are used. Some of these pesticides lack target specificity and can cause adverse effects in non-target organisms. In order to evaluate the environmental risk of these products, the use of transplanted sentinel organisms avoids side-effects from past events and facilitate comparison of multiple sites in a short time. We released specimens of the terrestrial snail Xeropicta derbentina in each 5 of two kinds of apple orchards with either conventional or organic management strategies plus in a single abandoned orchard. After one month, individuals were retrieved in order to measure acetylcholinesterase (AChE) activity. Mean values of AChE activity were significantly reduced in all conventional apple orchards compared to the others. Results show that the measurement of biomarkers such as AChE inhibition in transplated X. derbentina could be useful in the environmental risk assessment of post-authorized pesticides. - Snails as sentinel species to evaluate insecticide impacts in apple orchards.

  1. The Nature of Activated Non-classical Hydrogen Bonds: A Case Study on Acetylcholinesterase-Ligand Complexes.

    Berg, Lotta; Mishra, Brijesh Kumar; Andersson, C David; Ekström, Fredrik; Linusson, Anna

    2016-02-01

    Molecular recognition events in biological systems are driven by non-covalent interactions between interacting species. Here, we have studied hydrogen bonds of the CH⋅⋅⋅Y type involving electron-deficient CH donors using dispersion-corrected density functional theory (DFT) calculations applied to acetylcholinesterase-ligand complexes. The strengths of CH⋅⋅⋅Y interactions activated by a proximal cation were considerably strong; comparable to or greater than those of classical hydrogen bonds. Significant differences in the energetic components compared to classical hydrogen bonds and non-activated CH⋅⋅⋅Y interactions were observed. Comparison between DFT and molecular mechanics calculations showed that common force fields could not reproduce the interaction energy values of the studied hydrogen bonds. The presented results highlight the importance of considering CH⋅⋅⋅Y interactions when analysing protein-ligand complexes, call for a review of current force fields, and opens up possibilities for the development of improved design tools for drug discovery. PMID:26751405

  2. Effects of chlorpyrifos ethyl on acetylcholinesterase activity in climbing perch cultured in rice fields in the Mekong Delta, Vietnam.

    Nguyen, Tam Thanh; Berg, Håkan; Nguyen, Hang Thi Thuy; Nguyen, Cong Van

    2015-07-01

    Climbing perch is commonly harvested in rice fields and associated wetlands in the Mekong Delta. Despite its importance in providing food and income to local households, there is little information how this fish species is affected by the high use of pesticides in rice farming. Organophosphate insecticides, such as chlorpyrifos ethyl, which are highly toxic to aquatic organisms, are commonly used in the Mekong Delta. This study shows that the brain acetylcholinesterase (AChE) activity in climbing perch fingerlings cultured in rice fields, was significantly inhibited by a single application of chlorpyrifos ethyl, at doses commonly applied by rice farmers (0.32-0.64 kg/ha). The water concentration of chlorpyrifos ethyl decreased below the detection level within 3 days, but the inhibition of brain AChE activity remained for more than 12 days. In addition, the chlorpyrifos ethyl treatments had a significant impact on the survival and growth rates of climbing perch fingerlings, which were proportional to the exposure levels. The results indicate that the high use of pesticides among rice farmers in the Mekong Delta could have a negative impact on aquatic organisms and fish yields, with implications for the aquatic biodiversity, local people's livelihoods and the aquaculture industry in the Mekong Delta. PMID:25828891

  3. The activity of detoxifying enzymes in the infective juveniles of Heterorhabditis bacteriophora strains: Purification and characterization of two acetylcholinesterases.

    Mohamed, Magda A; Mahdy, El-Sayed M E; Ghazy, Abd-El-Hady M; Ibrahim, Nihal M; El-Mezayen, Hatem A; Ghanem, Manal M E

    2016-02-01

    The infectivity and detoxifying enzyme activities including glutathione-S-transferase (GST), acetylcholinesterase (AChE) and carboxylesterase (CaE) are investigated in the infective juveniles (IJs) of six different strains of Heterorhabditis bacteriophora as a biocontrol agent against insect pests. The specific activities ranged from 10.8-29.8 and 50-220units/mg protein for GST and AChE, respectively; and from 24.7-129 and 22.6-77.3units/mg protein for CaE as estimated by P-nitrophenyl and α-naphthyl acetates, respectively. H. bacteriophora EM2 strain has the highest infectivity and the highest enzymatic activities as well. AChE is the predominant detoxifying enzyme that might imply its major role in the detoxification of insecticide(s). The isoenzyme pattern demonstrated two major slow-moving isoforms in all EPN strains examined. Purification of two AChE isoforms, AChEAII and AChEBI, from H. bacteriophora EM2 strain is performed by ammonium sulfate precipitation, gel filtration on Sephacryl S-200 and chromatography on DEAE-Sepharose. AChEAII and AChEBII have specific activities of 1207 and 1560unit/mg protein, native molecular weights of 180 and 68kDa, and are found in dimeric and monomeric forms, respectively. Both isoforms showed optimum activity at pH8.5 and 35°C. AChEBI exhibited higher thermal stability and higher activation energy than AChEAII. The enzymatic activities of purified AChEs are completely inhibited by Hg(+2) and Ni(+2) and greatly enhanced by Mn(+2). The substrate specificity, the relative efficiency of substrates hydrolysis, substrate inhibition and inhibition by BW284C51, but not by iso-OMPA, clearly indicated that they are true AChEs; their properties are compared with those recorded for insects as target hosts for H. bacteriophora EM2. PMID:26545490

  4. Correlation of acetylcholinesterase activity in the brain and blood of wistar rats acutely infected with Trypanosoma congolense

    Habila N; Inuwa HM; Aimola IA; Lasisi OI; Chechet DG; Okafor IA

    2012-01-01

    Objective: To investigate the neurotransmitter enzyme Acetylcholinesterase (AChE) activity in the brain and blood of rats infected with Trypanosoma congolense (T. congo). Methods: Presence and degree of parasitemia was determined daily for each rat by the rapid matching method. AChE activity was determined by preparing a reaction mixture of brain homogenate and whole blood with 5, 5-dithiobisnitrobenzioc acid (DTNB or Ellman’s reagent) and Acetylthiocholine (ATC). The increase in absorbance was recorded at 436 nm over 10 min at 2 min intervals. Trypanosome species identification (before inoculation and on day 10 post infection) was done by Polymerase chain reaction using specific primers. Results: The AChE activity in the brain and blood decreased significantly as compared with the uninfected control. The AChE activity dropped to 0.32 from 2.20 μmol ACTC min-1mg protein-1 in the brain and 4.57 to 0.76 μmol ACTC min-1mg protein-1 in the blood. The animals treated with Diminaveto at 3.5 mg/kg/d were observed to have recovered significantly from parasitemia and were able to regain AChE activity in the blood but not in the brain as compared to the control groups. We also observed, that progressive parasitemia resulted to alterations in PCV, Hb, RBC, WBC, neurophils, total protein, lymphocytes, monocytes and eosinophil in acute infections of T. congo. Polymerase chain reaction (PCR) of infected blood before inoculation and on day 10 post infection revealed 600 bp on agarose gel electrophoresis. Conclusions: This finding suggest that decrease in AChE activity increases acetylcholine concentration in the synaptic cleft resulting to neurological failures in impulse transfer in T. congo infection rats.

  5. ACETYLCHOLINESTERASE HISTOCHEMISTRY OF THE THALAMUS IN THE PRIMATE

    2001-01-01

    Objective To observe the distribution of acetylcholinesterase activity in the thalamus of the monkey.Methods Histochemical method was used to detect the acetylcholinesterase activity in the thalamus.Results Acetylcholinesterase was found to be inhomogeneous distribution in the primate thalamus and to reveal previously uncovered inhomogeneity within certain thalamic nuclei and their subdivisions. The medial, ventral and posterior nuclear groups displayed markedly uneven acetylcholinesterase reaction.In the mediodorsal nucleus,three distinct sbudivisions were revealed by acetylcholinesterase histochemistry, medial magnocellular part, ventral sector of central parvicellular part and dorsolateral sector of lateral pars multiformity showed weak, moderate and strong acetylcholinesterase activity, respectively. In the ventral nuclear group, acetylcholinesterase histochemistry was strong in the medial part of ventral posterior nucleus, moderate in the magnocellular part of ventral anterior, caudal, medial, oral and pars postrema parts of ventral lateral nucleus, as well as lateral part of ventral posterior nucleus, poor and weak in the inferior part of ventral posterior nucleus, par compacta of the medial part of ventral posterior nucleus and parvicellular part of ventral anterior nucleus. In the pulvinar nucleus, acetylcholinesterase reaction ranged from weak, moderate to strong in the parts of the oral, medial and lateral, as well as inferior of this nucleus, respectively. Regional variations of acetylcholinesterase activity within the thalamic nuclei and their subdivisions can help to identify them by acetylcholinesterase histochemistry. In addition, the dark patches of strong acetylcholinesterase activity contrasting with a lighter surrounding matrix were revealed within the parvicellular part and pars multiformis of mediodorsal nucleus, paracentral nucleus, central lateral nucleus, pars postrema part of ventral lateral nucleus and medial habenula nucleus, as well as

  6. Histochemical demonstration of acetylcholinesterase in neuroblastoma.

    Variend, S; Loughlin, M A

    1984-01-01

    The presence of acetylcholinesterase in the tumour cells of neuroblastoma has been shown by enzyme histochemistry. For comparison, some other tumours likely to be found in children and commonly presenting histologically as small cell tumours have also been studied. Acetylcholinesterase activity was seen in rhabdomyosarcoma, but, compared with neuroblastoma, the activity was focal and sparse. One Ewing's tumour and a lymphoblastic lymphoma were negative for the enzyme reaction. Some of the ult...

  7. Silibinin inhibits acetylcholinesterase activity and amyloid β peptide aggregation: a dual-target drug for the treatment of Alzheimer's disease.

    Duan, Songwei; Guan, Xiaoyin; Lin, Runxuan; Liu, Xincheng; Yan, Ying; Lin, Ruibang; Zhang, Tianqi; Chen, Xueman; Huang, Jiaqi; Sun, Xicui; Li, Qingqing; Fang, Shaoliang; Xu, Jun; Yao, Zhibin; Gu, Huaiyu

    2015-05-01

    Alzheimer's disease (AD) is characterized by amyloid β (Aβ) peptide aggregation and cholinergic neurodegeneration. Therefore, in this paper, we examined silibinin, a flavonoid extracted from Silybum marianum, to determine its potential as a dual inhibitor of acetylcholinesterase (AChE) and Aβ peptide aggregation for AD treatment. To achieve this, we used molecular docking and molecular dynamics simulations to examine the affinity of silibinin with Aβ and AChE in silico. Next, we used circular dichroism and transmission electron microscopy to study the anti-Aβ aggregation capability of silibinin in vitro. Moreover, a Morris Water Maze test, enzyme-linked immunosorbent assay, immunohistochemistry, 5-bromo-2-deoxyuridine double labeling, and a gene gun experiment were performed on silibinin-treated APP/PS1 transgenic mice. In molecular dynamics simulations, silibinin interacted with Aβ and AChE to form different stable complexes. After the administration of silibinin, AChE activity and Aβ aggregations were down-regulated, and the quantity of AChE also decreased. In addition, silibinin-treated APP/PS1 transgenic mice had greater scores in the Morris Water Maze. Moreover, silibinin could increase the number of newly generated microglia, astrocytes, neurons, and neuronal precursor cells. Taken together, these data suggest that silibinin could act as a dual inhibitor of AChE and Aβ peptide aggregation, therefore suggesting a therapeutic strategy for AD treatment. PMID:25771396

  8. Altered binding of thioflavin t to the peripheral anionic site of acetylcholinesterase after phosphorylation of the active site by chlorpyrifos oxon or dichlorvos

    The peripheral anionic site of acetylcholinesterase, when occupied by a ligand, is known to modulate reaction rates at the active site of this important enzyme. The current report utilized the peripheral anionic site specific fluorogenic probe thioflavin t to determine if the organophosphates chlorpyrifos oxon and dichlorvos bind to the peripheral anionic site of human recombinant acetylcholinesterase, since certain organophosphates display concentration-dependent kinetics when inhibiting this enzyme. Incubation of 3 nM acetylcholinesterase active sites with 50 nM or 2000 nM inhibitor altered both the Bmax and Kd for thioflavin t binding to the peripheral anionic site. However, these changes resulted from phosphorylation of Ser203 since increasing either inhibitor from 50 nM to 2000 nM did not alter further thioflavin t binding kinetics. Moreover, the organophosphate-induced decrease in Bmax did not represent an actual reduction in binding sites, but instead likely resulted from conformational interactions between the acylation and peripheral anionic sites that led to a decrease in the rigidity of bound thioflavin t. A drop in fluorescence quantum yield, leading to an apparent decrease in Bmax, would accompany the decreased rigidity of bound thioflavin t molecules. The organophosphate-induced alterations in Kd represented changes in binding affinity of thioflavin t, with diethylphosphorylation of Ser203 increasing Kd, and dimethylphosphorylation of Ser203 decreasing Kd. These results indicate that chlorpyrifos oxon and dichlorvos do not bind directly to the peripheral anionic site of acetylcholinesterase, but can affect binding to that site through phosphorylation of Ser203

  9. Effects of metals on blood oxidative stress biomarkers and acetylcholinesterase activity in dice snakes (Natrix tessellata from Serbia

    Gavrić Jelena P.

    2015-01-01

    Full Text Available The effects of waterborne metals in water on the activities of blood copper-zinc superoxide dismutase (CuZnSOD, catalase (CAT, glutathione peroxidase (GSH-Px, glutathione reductase (GR, glutathione-S-transferase (GST, and acetylcholinesterase (AChE, and on the concentrations of total glutathione (GSH and lipid peroxides (TBARS in the blood of dice snakes (Natrix tessellata caught in Obedska Bara, Sebia (control area, with snakes caught in Pančevački Rit, a contaminated area in Serbia were examined. The activities of CAT, GSH-Px, GR and AChE, and the concentration of TBARS were significantly decreased, while GST activity and GSH concentration were significantly increased in snakes from the contaminated area compared to specimens from the control area. Significantly increased concentrations of Al, As, B, Ba, Ca, Cu, Fe, K, Li, Mn, Na, Ni and Zn in the water at the contaminated area as compared to control area were detected. The metals Ag, Bi, Cd, Co, Hg, In and Tl were not observed in any of the localities. Cr, Mo and Pb were not detected at the control area but were observed at the contaminated area. The concentrations of Sr were similar at both sites. The concentration of Mg was 2-fold higher at the control site than at the contaminated area. The obtained results show that most of the investigated blood biomarkers correlate with concentrations of metals present in the environment. These findings suggest that dice snakes are sensitive bioindicator species for monitoring the effects of increased metal concentrations in the environment. [Projekat Ministarstva nauke Republike Srbije, br. 173041 i br. 173043

  10. Effect of Neemta 2100 toxicity on acetylcholinesterase and serum glutamate oxaloacetate transaminase enzymes in serum of fish, Oreochromis mossambicus

    Parveen, M.; Sharma, R.; Kumar, S.

    2004-01-01

    Acetylcholinesterase and serum glutamate oxaloacetate transaminase enzymes have been used as marker monitoring the effect of neem seed based pesticide Neemta 2100 on the fish, Oreochromis mossambicus. Fishes exposed to sublethal concentrations of Neemta 2100 for acute periods of 24 and 48 hours were sacrificed to determine enzyme activities in serum affected due to toxicity. Laboratory studies of in vivo exposure of this pesticide showed synergistic inhibitory effect during acute period of to...

  11. An optimized extraction technique for acetylcholinesterase inhibitors from the Camellia japonica seed cake by using response surface methodology.

    Kim, Jae Kyeom; Kim, Cho Rong; Lim, Ho-Jeong; Nam, Sang Hae; Joo, Ok Soo; Shin, Dong-Hoon; Shin, Eui-Cheol

    2014-01-01

    The response surface methodology (RSM) was used to optimize the extraction conditions for the acetylcholinesterase (AchE) inhibitory activity and extraction yield from Camellia japonica seed cake. Predicted values for AchE inhibition and extraction yield were 19.41 and 13.35%, respectively, which are in good agreement with the experimental values from validation, suggesting that RSM may provide a useful tool to optimization processes. PMID:25229864

  12. Irreversible thermal denaturation of Torpedo californica acetylcholinesterase.

    Kreimer, D. I.; Shnyrov, V. L.; Villar, E.; Silman, I.; Weiner, L

    1995-01-01

    Thermal denaturation of Torpedo californica acetylcholinesterase, a disulfide-linked homodimer with 537 amino acids in each subunit, was studied by differential scanning calorimetry. It displays a single calorimetric peak that is completely irreversible, the shape and temperature maximum depending on the scan rate. Thus, thermal denaturation of acetylcholinesterase is an irreversible process, under kinetic control, which is described well by the two-state kinetic scheme N-->D, with activation...

  13. Studies on the In Vitro Antiproliferative, Antimicrobial, Antioxidant, and Acetylcholinesterase Inhibition Activities Associated with Chrysanthemum coronarium Essential Oil

    Sanaa K. Bardaweel

    2015-01-01

    Full Text Available The essential oil of the Jordanian Chrysanthemum coronarium L. (garland was isolated by hydrodistillation from dried flowerheads material. The oil was essayed for its in vitro scavenging activity using the 1,1-diphenyl-2-picrylhydrazyl (DPPH method. The results demonstrate that the oil exhibits moderate radical scavenging activity relative to the strong antioxidant ascorbic acid. In addition, cholinesterase inhibitory activity of C. coronarium essential oil was evaluated for the first time. Applying Ellman’s colorimetric method, interesting cholinesterase inhibitory activity, which is not dose dependent, was evident for the oil. Furthermore, antimicrobial activities of the oil against both Gram-negative and Gram-positive bacteria were evaluated. While it fails to inhibit Gram-negative bacteria growth, the antibacterial effects demonstrated by the oil were more pronounced against the Gram-positive strains. Moreover, the examined oil was assessed for its in vitro antiproliferative properties where it demonstrated variable activities towards different human cancer cell lines, of which the colon cancer was the most sensitive to the oil treatment.

  14. Rapid eye movement (REM sleep deprivation reduces rat frontal cortex acetylcholinesterase (EC 3.1.1.7 activity

    Camarini R.

    1997-01-01

    Full Text Available Rapid eye movement (REM sleep deprivation induces several behavioral changes. Among these, a decrease in yawning behavior produced by low doses of cholinergic agonists is observed which indicates a change in brain cholinergic neurotransmission after REM sleep deprivation. Acetylcholinesterase (Achase controls acetylcholine (Ach availability in the synaptic cleft. Therefore, altered Achase activity may lead to a change in Ach availability at the receptor level which, in turn, may result in modification of cholinergic neurotransmission. To determine if REM sleep deprivation would change the activity of Achase, male Wistar rats, 3 months old, weighing 250-300 g, were deprived of REM sleep for 96 h by the flower-pot technique (N = 12. Two additional groups, a home-cage control (N = 6 and a large platform control (N = 6, were also used. Achase was measured in the frontal cortex using two different methods to obtain the enzyme activity. One method consisted of the obtention of total (900 g supernatant, membrane-bound (100,000 g pellet and soluble (100,000 g supernatant Achase, and the other method consisted of the obtention of a fraction (40,000 g pellet enriched in synaptic membrane-bound enzyme. In both preparations, REM sleep deprivation induced a significant decrease in rat frontal cortex Achase activity when compared to both home-cage and large platform controls. REM sleep deprivation induced a significant decrease of 16% in the membrane-bound Achase activity (nmol thiocholine formed min-1 mg protein-1 in the 100,000 g pellet enzyme preparation (home-cage group 152.1 ± 5.7, large platform group 152.7 ± 24.9 and REM sleep-deprived group 127.9 ± 13.8. There was no difference in the soluble enzyme activity. REM sleep deprivation also induced a significant decrease of 20% in the enriched synaptic membrane-bound Achase activity (home-cage group 126.4 ± 21.5, large platform group 127.8 ± 20.4, REM sleep-deprived group 102.8 ± 14.2. Our results

  15. Antioxidant Activity and α-Glucosidase Inhibitory Activities of the Polycondensate of Catechin with Glyoxylic Acid.

    Sheng Geng

    Full Text Available In order to investigate polymeric flavonoids, the polycondensate of catechin with glyoxylic acid (PCG was prepared and its chemically antioxidant, cellular antioxidant (CAA and α-glucosidase inhibitory activities were evaluated. The DPPH and ABTS radical scavenging activities and antiproliferative effect of PCG were lower than those of catechin, while PCG had higher CAA activity than catechin. In addition, PCG had very high α-glucosidase inhibitory activities (IC50 value, 2.59 μg/mL in comparison to catechin (IC50 value, 239.27 μg/mL. Inhibition kinetics suggested that both PCG and catechin demonstrated a mixture of noncompetitive and anticompetitive inhibition. The enhanced CAA and α-glucosidase inhibitor activities of PCG could be due to catechin polymerization enhancing the binding capacity to the cellular membrane and enzymes.

  16. Antioxidant Activity and α-Glucosidase Inhibitory Activities of the Polycondensate of Catechin with Glyoxylic Acid

    Ma, Hanjun; Liu, Benguo

    2016-01-01

    In order to investigate polymeric flavonoids, the polycondensate of catechin with glyoxylic acid (PCG) was prepared and its chemically antioxidant, cellular antioxidant (CAA) and α-glucosidase inhibitory activities were evaluated. The DPPH and ABTS radical scavenging activities and antiproliferative effect of PCG were lower than those of catechin, while PCG had higher CAA activity than catechin. In addition, PCG had very high α-glucosidase inhibitory activities (IC50 value, 2.59 μg/mL) in comparison to catechin (IC50 value, 239.27 μg/mL). Inhibition kinetics suggested that both PCG and catechin demonstrated a mixture of noncompetitive and anticompetitive inhibition. The enhanced CAA and α-glucosidase inhibitor activities of PCG could be due to catechin polymerization enhancing the binding capacity to the cellular membrane and enzymes. PMID:26960205

  17. Post-irradiation changes in activities of acetylcholinesterase and butyrylcholinesterace due to ionizing radiation

    A review is presented of experimental studies, published in literature, of changes in the activities of both enzymes following irradiation. A number of mechanisms is listed involved in affecting the enzyme activity by irradiation. Data by various authors are classified according to the mammalian organs in which the effect of radiation was studied. The changes in activity are described in the liver and blood plasma, GIT, erythrocytes, and CNS in rats, rabbits, dogs, miniature swine, monkeys, guinea pigs, mice, and cats. The experimental animals were mainly irradiated with X and gamma radiation, in some cases with deuterons and protons. Radiation doses ranged within 3 and 200 Gy. (A.K.)

  18. "In vitro inhibition of human erythrocyte Acetylcholinesterase activity by Zinc and Mercury "

    "Abdollahi M

    2000-10-01

    Full Text Available The effects of zinc and mercury on human erythrocyte acetylcholinestrase activity were studied. Blood used in this study was obtained from 24 apparently healthy individuals and after hemolysation, was treted with 3 diferent concentrations of zinc and mercury. Significant suppressions in acetylcholinestrase activity were recorded in treated samples by zinc and mercury. When compared to controls the remaining activity was found to be 53% with the highest concen.tration of zinc (2.1 mg/dl, p<0.01, 72% with the middle (1.4 mg/dl, p<0.01 and 85% with the lowest one (0.7 mg/dl, p<0.01. in the case of mercury, the remaining activity was found to be 55% with the highest concentration (8.4 ng/g , p<0.01 , 72% with the middle (5.6 ng/g , p<0.01 and 79% with the lowest one (2.8 ng/g , p<0.01. mercury showed a good correlation between doses used and decreases in activity (r=0.98. zinc also showed a linear correlation ( r=0.99. the direct interaction of metal ions with acetylcholinestrase is proposed as a mechanism for depressed enzyme activity. It is concluded that zinc and mercury contamination during acetylcholinestrase measurement can be a source of error that must be taken in to account.

  19. Leukemia Inhibitory Factor Decreases the Arylamine N-Acetyltransferase Activity in Human Cumulus Granulosa Cells

    Chang, Chi-Chen; Hsieh, Yao-Yuan; CHUNG, JING-GUNG; Tsai, Horng-Der; Tsai, Chang-Hai

    2001-01-01

    Purpose: To evaluate the activities of acetyl coenzyme A (AcCoA): arylamine N-acetyltransferase (NAT) of intact cumulus granulosa cells and the role of leukemia inhibitory factor (LIF) upon their NAT activities.

  20. Modulation of the brain acetylcholinesterase activity after gamma irradiation or cytokine administration

    The central nervous system exhibits a functional radiosensitivity, with different abnormalities in the neuronal transmission. In particular we observed a decrease in AChE activity in the rat brain after a whole body gamma exposure. This could not be explained by a direct effect on the protein: the AChE is particularly radioresistant, since several hundred of grays are necessary to modify the in vitro enzymatic activity. Radiations have no effect on primary neuronal culture, and the in vivo radiogenic decrease in brain AChE activity could imply more complex mechanisms than nervous transmissions alone, involving the participation of several intercellular communication systems. The second part of our experimental results showed that both peripheral or central administration of IL-6 can reproduce the decrease in the brain AChE activity observed after an irradiation. The role of inflammatory mediators in the acute radiation syndrome is now well documented. The way these cellular mediators could activate the CNS remains unclear. An induction of messengers of IL-1 and TNF in different brain areas has been recently demonstrated. However, it could be mentioned that, by using primary neuronal cultures, neither the membranes-bound nor the release enzyme activities were modified by incubation with IL-6. On the other hand, when the primary neurons were plated with a subculture of glial cells, the release of enzyme was greatly reduced during a few hours after incubation with IL-6, but the membrane-bound enzyme, which represent more than 90% of the total activity, was not modified. Hence, the mechanisms by which cytokines act on the CNS seem to be more complex, with the participation of glial cells. We suggest that the peripheral early inflammatory response which occurs after irradiation might participate in the nervous damage. (N.C.)

  1. Effect of doxorubicin and daunorubicin on the activity of acetylcholinesterase in acute lymphoblastic leukamia

    Background: Our study was based on the alteration in the Michaelis Mentin parameters Apparent Michaelis Constant (aKm) and Apparent Maximum Velocity (aVm), which reflects activity of actyl cholinesterase (AChE). This activity decreases in Acute Lymphoblastic Leukaemia (ALL). This decrease in aKm and aVm values shows bad prognosis. Similarly the anticancer drugs like Daunorubicin and Doxorubicin further decreases the aKm and aVm values which worsen the prognosis. The objective of this study was to determine and compare the extent of inhibition of Acetylcholine Esterase by Daunorubicin and Doxorubicin in ALL. Methods: Study of 100 patients including both male and female children who's age ranged from 4 to 8 years and were advised doxorubicin and daunorubicin separately were tested by Ellman's method using acetylcholine iodide as substrate and 5,5-dithiobis 2-nitrobenzine as a colour reagent regardless of dose regimen i.e. (once in 3 week, small dose per week or a continuous infusion for 72 to 96 hours. Results: In this study the Michaelis Mentin parameters Apparent Michaelis Constant (aKm) and Apparent Maximum Velocity (aVm) of the enzyme were estimated both in normal individuals and in the patients and also during treatment with daunorubicin and doxorubicin. The value of Michaelis Mentin parameters, aKm, aVm and percentage activity of the enzyme in normal individual are 23, 70, and 100 respectively. The values of aKm, aVm and percentage activity of the enzyme were also estimated in the patients before and after treatment. The values of aKm and aVm in patients of acute lymphoblastic leukaemia and percentage activity of enzyme is decreased. After the treatment with daunorubicin and doxorubicin the values and activity is further decreased. Conclusion: We conclude that the drugs under study both decrease the enzyme activity but daunorubicin inhibits the enzyme more than doxorubicin. (author)

  2. Assessment of acetylcholinesterase and butyrylcholinesterase activities in blood plasma of agriculture workers

    V Dhananjayan

    2012-01-01

    Full Text Available Background: Cholinesterase determination indicates whether the person has been under pesticide exposure is not. It is recommended that the worker′s cholinesterase level should be assessed for workers at a pesticide applied region. Hence, cholinesterase activities in blood samples of agricultural workers exposed to vegetables and grape cultivation with age matched, unexposed workers, who never had any exposure to pesticides, were estimated. Methods: The detailed occupational history and lifestyle characters were obtained by questionnaire. Cholinesterase activity was determined by the method of Ellman as modified by Chambers and Chambers. Results: AChE was ranging from 1.65 to 3.54μmoles/min/ml in exposed subjects where as it was ranged from 2.22 to 3.51μmoles/min/ml in control subjects. BChE activity was ranging from 0.16 to 5.2μmoles/min/ml among exposed subjects, where as it was ranged from 2.19 to 5.06μmoles/min/ml in control subjects. The results showed statistically significant reduction in enzyme activities (AChE 14%; BChE 56% among exposed subjects. Conclusion: It was concluded that the reduction in cholinesterase activity may lead to varieties of effects. Hence it is compulsory to use protective gadgets during pesticide spray. Further a continuous biomonitoring study is recommended to assess pesticide exposure.

  3. Coimmobilization of acetylcholinesterase and choline oxidase on gold nanoparticles: stoichiometry, activity, and reaction efficiency.

    Keighron, Jacqueline D; Åkesson, Sebastian; Cans, Ann-Sofie

    2014-09-30

    Hybrid structures constructed from biomolecules and nanomaterials have been used in catalysis and bioanalytical applications. In the design of many chemically selective biosensors, enzymes conjugated to nanoparticles or carbon nanotubes have been used in functionalization of the sensor surface for enhancement of the biosensor functionality and sensitivity. The conditions for the enzyme:nanomaterial conjugation should be optimized to retain maximal enzyme activity, and biosensor effectiveness. This is important as the tertiary structure of the enzyme is often altered when immobilized and can significantly alter the enzyme catalytic activity. Here we show that characterization of a two-enzyme:gold nanoparticle (AuNP) conjugate stoichiometry and activity can be used to gauge the effectiveness of acetylcholine detection by acetylcholine esterase (AChE) and choline oxidase (ChO). This was done by using an analytical approach to quantify the number of enzymes bound per AuNP and monitor the retained enzyme activity after the enzyme:AuNP synthesis. We found that the amount of immobilized enzymes differs from what would be expected from bulk solution chemistry. This analysis was further used to determine the optimal ratio of AChE:ChO added at synthesis to achieve optimum sequential enzyme activity for the enzyme:AuNP conjugates, and reaction efficiencies of greater than 70%. We here show that the knowledge of the conjugate stoichiometry and retained enzyme activity can lead to more efficient detection of acetylcholine by controlling the AChE:ChO ratio bound to the gold nanoparticle material. This approach of optimizing enzyme gold nanoparticle conjugates should be of great importance in the architecture of enzyme nanoparticle based biosensors to retain optimal sensor sensitivity. PMID:25167196

  4. The Assembly of Proline-rich Membrane Anchor (PRiMA)-linked Acetylcholinesterase Enzyme: GLYCOSYLATION IS REQUIRED FOR ENZYMATIC ACTIVITY BUT NOT FOR OLIGOMERIZATION*

    Chen, Vicky P.; Choi, Roy C. Y.; Chan, Wallace K. B.; Leung, K. Wing; Guo, Ava J. Y.; Gallant K. L. Chan; Luk, Wilson K. W.; Tsim, Karl W. K.

    2011-01-01

    Acetylcholinesterase (AChE) anchors onto cell membranes by a transmembrane protein PRiMA (proline-rich membrane anchor) as a tetrameric form in vertebrate brain. The assembly of AChE tetramer with PRiMA requires the C-terminal “t-peptide” in AChE catalytic subunit (AChET). Although mature AChE is well known N-glycosylated, the role of glycosylation in forming the physiologically active PRiMA-linked AChE tetramer has not been studied. Here, several lines of evidence indicate that the N-linked ...

  5. Sesquiterpenes produced by endophytic fungus Phomopsis cassiae with antifungal and acetylcholinesterase inhibition activities; Sesquiterpenos produzidos pelo fungo endofitico Phomopsis cassiae com atividade antifungica e inibidora de acetilcolinesterase

    Zanardi, Lisineia M.; Bolzani, Vanderlan da S.; Cavalheiro, Alberto J.; Silva, Dulce H. Siqueira; Trevisan, Henrique C.; Araujo, Angela R. [UNESP, Araraquara, SP (Brazil). Inst. de Quimica; Silva, Geraldo H. [Universidade Federal de Sergipe (UFS), Aracaju, SE (Brazil). Centro de Ciencias Exatas e Tecnologia; Teles, Helder L. [Universidade Federal do Mato Grosso (UFMT), Rondonopolis, MT (Brazil). Dept. de Ciencias Biologicas; Young, Maria Claudia M., E-mail: araujoar@iq.unesp.br [Instituto de Botanica, Sao Paulo, SP (Brazil). Seccao de Fisiologia e Bioquimica de Plantas

    2012-07-01

    Two new diastereoisomeric cadinanes sesquiterpenes 3,9-dihydroxycalamenene (1-2), along with the known 3-hydroxycalamen-8-one (3) and aristelegone-A (4), were isolated from ethyl acetate extract of Phomopsis cassiae, an endophytic fungus in Cassia spectabilis. Their structures, including relative stereochemistry, were determined on the basis of detailed interpretation of 2D NMR spectra and comparison with related known compounds. Compounds 1-4 displayed antifungal activity against the phytopathogenic fungi Cladosporium cladosporioides and C. sphaerospermum, as well as inhibition of acetylcholinesterase. (author)

  6. Effect of Donepezil, Tacrine, Galantamine and Rivastigmine on Acetylcholinesterase Inhibition in Dugesia tigrina

    Cristiane Bezerra da Silva

    2016-01-01

    Full Text Available Dugesia tigrina is a non-parasitic platyhelminth, which has been recently utilized in pharmacological models, regarding the nervous system, as it presents a wide sensitivity to drugs. Our trials aimed to propose a model for an in vivo screening of substances with inhibitory activity of the enzyme acetylcholinesterase. Trials were performed with four drugs commercialized in Brazil: donepezil, tacrine, galantamine and rivastigmine, utilized in the control of Alzheimer’s disease, to inhibit the activity of acetylcholinesterase. We tested five concentrations of the drugs, with an exposure of 24 h, and the mortality and the inhibition of acetylcholinesterase planarian seizure-like activity (pSLA and planarian locomotor velocity (pLMV were measured. Galantamine showed high anticholinesterasic activity when compared to the other drugs, with a reduction of 0.05 μmol·min−1 and 63% of convulsant activity, presenting screw-like movement and hypokinesia, with pLMV of 65 crossed lines during 5 min. Our results showed for the first time the anticholinesterasic and convulsant effect, in addition to the decrease in locomotion induced by those drugs in a model of invertebrates. The experimental model proposed is simple and low cost and could be utilized in the screening of substances with anticholinesterasic action.

  7. ALTERATIONS IN THE ACETYLCHOLINESTERASE ACTIVITY IN THE BRAIN OF ALBINO MICE EXPOSED TO ACEPHATE

    M. SIVA PRASAD

    2013-01-01

    Full Text Available Acephate (AP, a widely available organophosphorus (OP insecticide, has low mammalian toxicity and isconsidered non-phytotoxic on many crop plants and therefore it is preferred in agricultural crops. In plants andinsects, AP is metabolized extensively to methamidophos (MP, a more potent OP insecticide. The limitedmammalian metabolism of AP to MP has been studied in laboratory rat models and suggests that initial formationof MP from AP may inhibit further formation. Hence in the present investigation we have studied the effect of anAP in cholinergic mechanisms in the different regions of brain. For the present study the male mice were exposedto 1/10th LD50 of AP via oral gavage (i.e. 40.5mg/kg body weight. Our results indicate a steady decline of AChEactivity in all the regions of the brain of Acephate exposed animals. As expected an increase in ACh activity wasnoticed in all the regions of the AP exposed animals. We suggest that cholinergic system is seriously affected bythe intoxication of Acephate and the effect was more effective in 30 days when compared to 10 days

  8. Recombinant human migration inhibitory factor has adjuvant activity.

    Weiser, W Y; Pozzi, L M; Titus, R G; David, J R

    1992-01-01

    Recombinant human migration inhibitory factor (MIF), isolated through functional expression cloning in COS-1 cells, up-regulates expression of genes encoding HLA-DR and interleukin 1 beta (IL-1 beta) and elaboration of IL-1 beta by human monocyte-derived macrophages. Administration of soluble bovine serum albumin or human immunodeficiency virus 120-kDa glycoprotein (HIV gp120) to mice in the presence of recombinant MIF together with incomplete Freund's adjuvant induced a strong T-cell prolife...

  9. Concentration-dependent interactions of the organophosphates chlorpyrifos oxon and methyl paraoxon with human recombinant acetylcholinesterase

    For many decades it has been thought that oxygen analogs (oxons) of organophosphorus insecticides phosphorylate the catalytic site of acetylcholinesterase by a mechanism that follows simple Michaelis-Menten kinetics. More recently, the interactions of at least some oxons have been shown to be far more complex and likely involve binding of oxons to a second site on acetylcholinesterase that modulates the inhibitory capacity of other oxon molecules at the catalytic site. The current study has investigated the interactions of chlorpyrifos oxon and methyl paraoxon with human recombinant acetylcholinesterase. Both chlorpyrifos oxon and methyl paraoxon were found to have k i's that change as a function of oxon concentration. Furthermore, 10 nM chlorpyrifos oxon resulted in a transient increase in acetylthiocholine hydrolysis, followed by inhibition. Moreover, in the presence of 100 nM chlorpyrifos oxon, acetylthiocholine was found to influence both the K d (binding affinity) and k 2 (phosphorylation constant) of this oxon. Collectively, these results demonstrate that the interactions of chlorpyrifos oxon and methyl paraoxon with acetylcholinesterase cannot be described by simple Michaelis-Menten kinetics but instead support the hypothesis that these oxons bind to a secondary site on acetylcholinesterase, leading to activation/inhibition of the catalytic site, depending on the nature of the substrate and inhibitor. Additionally, these data raise questions regarding the adequacy of estimating risk of low levels of insecticide exposure from direct extrapolation of insecticide dose-response curves since the capacity of individual oxon molecules at low oxon levels could be greater than individual oxon molecules in vivo associated with the dose-response curve

  10. Determination of antigenicity by radioimmunoassay and of trypsin inhibitory activities in heat or enzyme denatured ovomucoid

    The effects of heat treatment and enzymic digestion on the antigenic reactivity of ovomucoid were studied. This reactivity was mainly examined by a solid phase competitive radioimmunoassay. The trypsin inhibitory activity was also measured to elucidate its relationship to the antigenic reactivity. The antigenic reactivity and trypsin inhibitory activity diminished in parallel with increase of heating time. However, enzymic digestion caused a more rapid decrease in antigenic reactivity than in trypsin inhibitory activity. From these results, it is suggested that the structure of the antigenic determinants is destroyed in a similar manner to that of the trypsin inhibitory active site when ovomucoid is heated, while the former structure is destroyed more easily than the latter by enzymic digestion

  11. Acetylcholinesterase: diffusional encounter rate constants for dumbbell models of ligand.

    Antosiewicz, J; Gilson, M K; Lee, I H; McCammon, J A

    1995-01-01

    For some enzymes, virtually every substrate molecule that encounters the entrance to the active site proceeds to reaction, at low substrate concentrations. Such diffusion-limited enzymes display high apparent bimolecular rate constants ((kcat/KM)), which depend strongly upon solvent viscosity. Some experimental studies provide evidence that acetylcholinesterase falls into this category. Interestingly, the asymmetric charge distribution of acetylcholinesterase, apparent from the crystallograph...

  12. Contributions of Diverse Excitatory and Inhibitory Neurons to Recurrent Network Activity in Cerebral Cortex

    Neske, Garrett T.; Patrick, Saundra L.; Connors, Barry W.

    2015-01-01

    The recurrent synaptic architecture of neocortex allows for self-generated network activity. One form of such activity is the Up state, in which neurons transiently receive barrages of excitatory and inhibitory synaptic inputs that depolarize many neurons to spike threshold before returning to a relatively quiescent Down state. The extent to which different cell types participate in Up states is still unclear. Inhibitory interneurons have particularly diverse intrinsic properties and synaptic...

  13. Polysaccharide with antioxidant, α-amylase inhibitory and ACE inhibitory activities from Momordica charantia.

    Tan, Hwee-Feng; Gan, Chee-Yuen

    2016-04-01

    Functional polysaccharide was isolated from Momordica charantia, with a yield of 36% (w/w). M. charantia bioactive polysaccharide (MCBP) was an acidic and branched heteropolysaccharide with a molecular weight of 92 kDa. Fourier transform infrared spectroscopic analysis indicated that MCBP was a pectin-like polysaccharide with an esterification degree of 53% and it contains numerous monosaccharides, predominantly glucose, galactose, and galaturonic acid. The results also showed that MCBP exhibited free radical scavenging activity (31.9%), ferric reducing antioxidant power (0.95 mM), α-amylase inhibition (89.1%), and angiotensin-converting enzyme inhibition (94.1%). In the terms of functionality, MCBP showed a lower water-holding capacity but higher in oil-holding capacity, emulsifying activity and foaming capacity compared to citrus pectin. Scanning electron microscopy images demonstrated that MCBP formed gels with a porous structure, and flow analysis showed that the gel solution exhibited pseudoplastic shear-thinning behavior. These findings indicated that MCBP is a promising functional macromolecular carbohydrate for the food and nutraceutical industries. PMID:26778156

  14. Effect of C-547 (a novel acetylcholinesterase inhibitor) on AChE activity in striated and heart muscles

    Říčný, Jan; Nikolsky, E. E.; Vyskočil, František; Soukup, Tomáš

    Les Arcs : EWCBR, 2008. s. 77-77. [European winter conference on brain research /28./. 08.03.2008-15.03.2008, Les Arcs] R&D Projects: GA ČR(CZ) GA304/05/0327; GA AV ČR(CZ) IAA5011411 Grant ostatní: Myores(XE) 511978 Institutional research plan: CEZ:AV0Z50110509 Source of funding: R - rámcový projekt EK Keywords : spo2 * acetylcholinesterase inhibitors * 6-methyluracil derivatives * skeletal muscles Subject RIV: ED - Physiology

  15. Effect of C-547 (a novel acetylcholinesterase inhibitor) on AChE activity in striated and heart muscles

    Říčný, Jan; Nikolsky, E. E.; Petrov, K. A.; Vyskočil, František; Soukup, Tomáš

    Fyziologický ústav AV ČR, v. v. i.. Roč. 57, č. 2 (2008), 29P-29P ISSN 0862-8408. [Fyziologické dny /84./. 06.02.2008-08.02.2008, Martin] R&D Projects: GA ČR(CZ) GA304/05/0327; GA AV ČR(CZ) IAA5011411 Grant ostatní: Myores(XE) 511978 Institutional research plan: CEZ:AV0Z50110509 Source of funding: R - rámcový projekt EK Keywords : cpo1 * acetylcholinesterase inhibitors * 6-methyluracil derivatives * skeletal muscles Subject RIV: FH - Neurology

  16. Effect of C-547 (a novel acetylcholinesterase inhibitor) on AChE activity in striated and heart muscles

    Říčný, Jan; Nikolsky, E. E.; Petrov, K. A.; Vyskočil, František; Soukup, Tomáš

    Martin : Univerzita Komenského, 2008. s. 111-111. [Fyziologické dny /84./. 06.02.2008-08.02.2008, Martin] R&D Projects: GA ČR(CZ) GA304/05/0327; GA AV ČR(CZ) IAA5011411 Grant ostatní: Myores(XE) 511978 Institutional research plan: CEZ:AV0Z50110509 Source of funding: R - rámcový projekt EK Keywords : spo2 * skeletal muscles * acetylcholinesterase * heart Subject RIV: FH - Neurology

  17. Acetylcholinesterase: Enhanced Fluctuations and Alternative

    Bui, Jennifer M.; Tai, Kaihsu; Mccammon, J Andrew A.

    2004-05-21

    A 15 ns molecular dynamics simulation is reported for the complex of mouse acetylcholinesterase (mAChE) and the protein neurotoxin fasciculin-2. As compared to a 15 ns simulation of apo-mAChE, the structural fluctuations of the enzyme are substantially increased in magnitude for the enzyme in the complex. Fluctuations of part of the long omega loop (residues 69-96) are particularly enhanced. This loop forms one wall of the active site, and the enhanced fluctuations lead to additional routes of access to the active site.

  18. Insecticidal and Enzyme Inhibitory Activities of Sparassol and Its Analogues against Drosophila suzukii.

    Kim, Junheon; Jang, Miyeon; Lee, Kyoung-Tae; Yoon, Kyungjae Andrew; Park, Chung Gyoo

    2016-07-13

    Drosophila suzukii is an economically important pest in America and Europe as well as in Asia. Sparassol and methyl orsellinate are naturally produced by the cultivating mushrooms Sparassis cripta and Sparassis latifolia. Fumigant and contact toxicities of synthetic sparassol and its analogues, methyl orsellinate and methyl 2,4-dimethoxy-6-methylbenzoate (DMB), were investigated. Negligible fumigant activity was observed from the tested compounds. However, DMB showed the strongest contact toxicity, followed by sparassol and methyl orsellinate. The possible modes of action of the compounds were assessed for their acetylcholinesterase (AChE)- and glutathione S-transferase (GST)-inhibiting activities. AChE activity was weakly inhibited by methyl orsellinate and DMB, but GST was inhibited by sparassol, methyl orsellinate, and DMB. Thus, DMB could be a promising alternative to common insecticides as it can be easily synthesized from sparassol, which is the natural product of Sparassis species. Sparassis species could be an industrial resource of DMB. PMID:27327201

  19. Structure–activity relationships of 44 halogenated compounds for iodotyrosine deiodinase-inhibitory activity

    The aim of this study was to investigate the possible influence of halogenated compounds on thyroid hormone metabolism via inhibition of iodotyrosine deiodinase (IYD) activity. The structure-activity relationships of 44 halogenated compounds for IYD-inhibitory activity were examined in vitro using microsomes of HEK-293 T cells expressing recombinant human IYD. The compounds examined were 17 polychlorinated biphenyls (PCBs), 15 polybrominated diphenyl ethers (PBDEs), two agrichemicals, five antiparasitics, two pharmaceuticals and three food colorants. Among them, 25 halogenated phenolic compounds inhibited IYD activity at the concentration of 1 × 10−4 M or 6 × 10−4 M. Rose bengal was the most potent inhibitor, followed by erythrosine B, phloxine B, benzbromarone, 4′-hydroxy-2,2′,4-tribromodiphenyl ether, 4-hydroxy-2,3′,3,4′-tetrabromodiphenyl ether, 4-hydroxy-2′,3,4′,5,6′-pentachlorobiphenyl, 4′-hydroxy-2,2′,4,5′-tetrabromodiphenyl ether, triclosan, and 4-hydroxy-2,2′,3,4′,5-pentabromodiphenyl ether. However, among PCBs and PBDEs without a hydroxyl group, including their methoxylated metabolites, none inhibited IYD activity. These results suggest that halogenated compounds may disturb thyroid hormone homeostasis via inhibition of IYD, and that the structural requirements for IYD-inhibitory activity include halogen atom and hydroxyl group substitution on a phenyl ring

  20. ANTICARIES AND α-AMYLASE INHIBITORY ACTIVITY OF JASMINUM ARBORESCENS ROXB. (OLEACEAE LEAVES EXTRACT

    Bhagath K

    2013-12-01

    Full Text Available The aim of the present study was to determine anti caries and α-amylase inhibitory activity of leaf extract of Jasminum arborescens Roxb. (Oleaceae. Anti caries activity was determined by Agar well diffusion assay against seven clinical isolates of Streptococcus mutans (Sm-01 to Sm-07 recovered from dental caries subjects. Enzyme inhibitory activity was tested against α-amylase by spectrophometric method using starch as substrate. The extract exhibited dose dependent inhibition against cariogenic isolates. Among seven isolates, isolate Sm-04 and Sm-06 were inhibited to higher and least extent respectively. The extract was found to cause inhibition of α-amylase activity in a dose dependent manner and its IC50 value was found to be 17.45 mg/ml. The inhibitory activity could be attributed to the presence of secondary metabolites. The plant may be a potential source for development of agents which are active against dental caries pathogens and for diabetes mellitus.

  1. Aphicidal Activity of Illicium verum Fruit Extracts and Their Effects on the Acetylcholinesterase and Glutathione S-transferases Activities in Myzus persicae (Hemiptera: Aphididae).

    Zhou, Ben-Guo; Wang, Sa; Dou, Ting-Ting; Liu, Su; Li, Mao-Ye; Hua, Ri-Mao; Li, Shi-Guang; Lin, Hua-Feng

    2016-01-01

    This study aims to explore the aphicidal activity and underlying mechanism of Illicium verum Hook. f. that is used as both food and medicine. The contact toxicity of the extracts from I. verum fruit with methyl alcohol (MA), ethyl acetate (EA), and petroleum ether (PE) against Myzus persicae (Sulzer), and the activities of acetylcholinesterase (AChE) and glutathione S-transferases (GSTs) of M. persicae after contact treatment were tested. The results showed that MA, EA, and PE extracts of 1.000 mg/l caused, respectively, M. persicae mortalities of 68.93%, 89.95% and 74.46%, and the LC50 of MA, EA, and PE extracts were 0.31, 0.14 and 0.27 mg/l at 72 h after treatment, respectively; the activities of AChE and GSTs in M. persicae were obviously inhibited by the three extracts, as compared with the control, with strong dose and time-dependent effects, the inhibition rates on the whole reached more than 50.00% at the concentration of 1.000 mg/l at 72 h after treatment. The inhibition of the extracts on AChE and GSTs activities (EA extract > PE extract > MA extract) were correlated with theirs contact toxic effects, so it is inferred that the decline of the metabolic enzymes activities may be one of important reasons of M. persicae death. The study results suggested that I. verum extracts have potential as a eco-friendly biopesticide in integrated pest management against M. persicae. PMID:26826651

  2. Acetylcholinesterase activity and catecholamine content in thymic and splenic nerve fibres of white rats long after chronic exposure to physical factors and application of interleukin-1β

    Acetylcholinesterase (AChE) activity and catecholamine (CA) content in nerve fibres of the thymus and spleen of white rats were studied 6 months after prolonged combined exposure to ionizing radiation and heat and after application of interleukin-1β (IL-1β). Combined action of the physical factors induced a certain decrease in AChE activity and increase in CA content in both organs. Application of the cytokine to animals exposed to radiation and heat elicited a more pronounced decrease in AChE in these lymphoid organs and increase, especially in the spleen, in CA. The results suggest about enhanced responsiveness of the autonomic nervous system to IL-1β animals which had been long before exposed to prolonged combined action of radiation and heat

  3. Effects of harmine, an acetylcholinesterase inhibitor, on spatial learning and memory of APP/PS1 transgenic mice and scopolamine-induced memory impairment mice.

    He, Dandan; Wu, Hui; Wei, Yue; Liu, Wei; Huang, Fei; Shi, Hailian; Zhang, Beibei; Wu, Xiaojun; Wang, Changhong

    2015-12-01

    Harmine, a β-carboline alkaloid present in Peganum harmala with a wide spectrum of pharmacological activities, has been shown to exert strong inhibition against acetylcholinesterase in vitro. However, whether it can rescue the impaired cognition has not been elucidated yet. In current study, we examined its effects on scopolamine-induced memory impairment mice and APP/PS1 transgenic mice, one of the models for Alzheimer's disease, using Morris Water Maze test. In addition, whether harmine could penetrate blood brain barrier, interact with and inhibit acetylcholinesterase, and activate downstream signaling network was also investigated. Our results showed that harmine (20mg/kg) administered by oral gavage for 2 weeks could effectively enhance the spatial cognition of C57BL/6 mice impaired by intraperitoneal injection of scopolamine (1mg/kg). Meanwhile, long-term consumption of harmine (20mg/kg) for 10 weeks also slightly benefited the impaired memory of APP/PS1 mice. Furthermore, harmine could pass through blood brain barrier, penetrate into the brain parenchyma shortly after oral administration, and modulate the expression of Egr-1, c-Jun and c-Fos. Molecular docking assay disclosed that harmine molecule could directly dock into the catalytic active site of acetylcholinesterase, which was partially confirmed by its in vivo inhibitory activity on acetylcholinesterase. Taken together, all these results suggested that harmine could ameliorate impaired memory by enhancement of cholinergic neurotransmission via inhibiting the activity of acetylcholinesterase, which may contribute to its clinical use in the therapy of neurological diseases characterized with acetylcholinesterase deficiency. PMID:26526348

  4. Use of acetylcholinesterase inhibitors in Alzheimer's disease.

    Moghul, S; Wilkinson, D

    2001-09-01

    Alzheimer's disease is a growing problem in an aging Western world, estimated to have cost the US economy USD 1.75 trillion. Until recently, the management of Alzheimer's disease largely comprised support for the family, nursing care and the use of unlicensed medication to control behavioral disturbances. The three new acetylcholinesterase inhibitors licensed to treat Alzheimer's disease (donepezil, rivastigmine and galantamine) have provided clinicians with a major impetus to their desire to diagnose and treat this lethal disease. Their effects on cognition are proven. More recent work on the effects of acetylcholinesterase inhibitors on behavioral symptoms, activities of daily living and caregiver burden have also been encouraging. Emerging work indicates their likely efficacy in other dementias (e.g., vascular dementia, dementia with Lewy bodies). This review summarizes the evidence concerning the impact of acetylcholinesterase inhibitors in dementia both currently and over the next 5 years. PMID:19811047

  5. Comparison of ACE inhibitory activity in skimmed goat and cow milk hydrolyzed by alcalase, flavourzyme, neutral protease and proteinase K

    Bao Chunju

    2016-06-01

    Full Text Available Angiotensin I converting enzyme (ACE inhibitory peptides derived from milk proteins have obvious effect of lowering blood pressure, safe and non-toxic side effects. This study compared four commercial proteases, namely alcalase, flavourzyme, neutral protease and proteinase K for their ACE inhibitory activity in skimmed goat and cow milk and identified the best one with higher ACE inhibitory activity. The degree of hydrolysis (DH of alcalase and proteinase K were much higher than flavourzyme, neutral protease for both skimmed goat and cow milk. Alcalase was the best enzyme to produce ACE inhibitory peptides from goat milk, with the ACE inhibitory activity 95.31%, while proteinase K was the optimal protease for hydrolyzing cow milk, with 81.28% ACE inhibitory activity. Furthermore, no correlation was obtained between the ACE inhibitory activity and DH for both goat and cow milk.

  6. Wild Argentinian Amaryllidaceae, a New Renewable Source of the Acetylcholinesterase Inhibitor Galanthamine and Other Alkaloids

    Gabriela E. Feresin

    2012-11-01

    Full Text Available The Amaryllidaceae family is well known for its pharmacologically active alkaloids. An important approach to treat Alzheimer’s disease involves the inhibition of the enzyme acetylcholinesterase (AChE. Galanthamine, an Amaryllidaceae alkaloid, is an effective, selective, reversible, and competitive AchE inhibitor. This work was aimed at studying the alkaloid composition of four wild Argentinian Amarillydaceae species for the first time, as well as analyzing their inhibitory activity on acetylcholinesterase. Alkaloid content was characterized by means of GC-MS analysis. Chloroform basic extracts from Habranthus jamesonii, Phycella herbertiana, Rhodophiala mendocina and Zephyranthes filifolia collected in the Argentinian Andean region all contained galanthamine, and showed a strong AChE inhibitory activity (IC50 between 1.2 and 2 µg/mL. To our knowledge, no previous reports on alkaloid profiles and AChEIs activity of wild Argentinian Amarillydaceae species have been publisihed. The demand for renewable sources of industrial products like galanthamine and the need to protect plant biodiversity creates an opportunity for Argentinian farmers to produce such crops.

  7. Inhibitory activity of Bifidobacterium adolescent combined with cisplatin on melanoma in mice and its mechanism

    2008-01-01

    The aim of this study is to explore inhibitory activity of Bifidobacterium adolescent combined with cisplatin on the growth of melanoma(B16)in mice and the underlying mechanism.C57 mice were inoculated with B16 cancer cells to construct mouse model of melanoma and treated with bifidobacterium adolescent combined with cisplatin.Ratios of inhibitory activity on the growth of melanoma(B 16)were calculated.Pathology changes of the tumor were observed by HE staining.B 16 cell cycles were examined on a flow cytometer.Lymphocyte proliferation was measured with MTT assay and the T-cell subset was measured by double marked fluorescence.When bifidobacterium of 1010 cfu/L was injected,the ratio of inhibitory activity on the growth of melanoma(B16)reached 54%,which was similar to that of cisplatin group.The ratio of inhibitory activity reached 74.45% when the mice were treated by bifidobacterium combined with cisplatin,HE staining shows that bifidobacterium inhibited B16 cell proliferation and enhanced the cisplati(n)s killing activity on B16 cells.The results of flow cytometry demonstrated that B16 cell proliferation was arrested at G1 stage after treatment with bifidobacterium.The B16 cell proliferation was arrested at S stage after treatment with cisplatin.The CD4+ percentage increased and the difference was significant compared with the normal group after treatment with bifidobacterium,indicating that T-cell immune activity was enhanced.Treatment with bifidobacterium combined with cisplatin can enhance the inhibitory activity on the growth of melanoma(B16)of cisplatin.The mechanism of the inhibitory activity on B 16 cell proliferation is correlated with the enhanced immune activity in mice.

  8. Use and disuse and the control of acetylcholinesterase activity in fast and slow twitch muscle of rat

    Dettbarn, W. D.; Groswald, D.; Gupta, R. C.; Misulis, K. E.

    1985-01-01

    The role of acetylcholinesterase (AChE) in neuromuscular transmission is relatively well established, little is known, however, of the mechanisms that regulate its synthesis and control its specific distribution in fast and slow muscle. Innervation plays an important role in the regulation of AChE and elimination of the influence of the nerve by surgical denervation results in a loss of AChE. The influences of the nerve and how they are mediated was investigated. It is suggested that muscle usage and other factors such as materials carried by axonal transport may participate in the regulation of this enzyme. The mechanisms that regulate AChE and its molecular forms in two functionally different forms are studied.

  9. C- and O-glycosyl flavonoids in Sanguinello and Tarocco blood orange (Citrus sinensis (L.) Osbeck) juice: Identification and influence on antioxidant properties and acetylcholinesterase activity.

    Barreca, Davide; Gattuso, Giuseppe; Laganà, Giuseppina; Leuzzi, Ugo; Bellocco, Ersilia

    2016-04-01

    Sanguinello and Tarocco are the blood orange (Citrus sinensis (L.) Osbeck) cultivars most diffused worldwide. Reversed phase liquid chromatography coupled with MS-MS analysis showed that these two varieties have a similar chromatographic pattern, characterised by the presence of C- and O-glycosyl flavonoids. Of the two, Sanguinello was found to be far richer in flavonoids than Tarocco. In the juices, twelve individual components were identified for the first time, namely, four C-glycosyl flavones (lucenin-2, vicenin-2, stellarin-2, lucenin-2 4'-methyl ether and scoparin), three flavonol derivatives (quercetin-3-O-(2-rhamnosyl)-rutinoside, quercetin-3-O-hexoside, quercetin 3-hydroxy-3-methylglutaryl-glycoside), an O-triglycosyl flavanone (narirutin 4'-O-glucoside) and a flavone O-glycosides (chrysoeriol 7-O-neoesperidoside). Moreover, the influence of the identified C- and O-glycosyl flavonoids on the antioxidant and acetylcholinesterase activity of these juices has been evaluated. PMID:26593535

  10. Purification and Determination of Inhibitory Activity of Recombinant Soyacystatin Against Papain and Fish Protease

    AKPINAR, Özlem

    2004-01-01

    Recombinant (r-) soyacystatin was characterized for its inhibitory activity against papain and compared to egg white cystatin. r-Soyacystatin expressed in E. coli was purified with phenyl-Sepharose and DEAE 4.33 fold as a recombinant protein. Egg white cystatin was purified by using affinity chromatography on cm-papain-Sepharose. Inhibitory activity of r-soyacystatin was similar to that of egg white cystatin. The amount required to inhibit 50% activity of papain used in the assay, 2 pg, was 0...

  11. Inhibitory activities of microalgal extracts against Epstein-Barr Virus (EBV antigen expression in lymphoblastoid cells

    Koh Yih Yih

    2014-01-01

    Full Text Available The inhibitory activities of microalgal extracts against the expression of three EBV antigens, latent membrane protein (LMP1, Epstein-Barr nuclear antigen (EBNA1 and Z Epstein-Barr reactivation activator (ZEBRA were assessed by immunocytochemistry. The observation that the methanol extracts and their fractions from Ankistrodesmus convolutus, Synechococcus elongatus and Spirulina platensis exhibited inhibitory activity against EBV proteins in three Burkitt’s lymphoma cell lines at concentrations as low as 20 μg/ml suggests that microalgae could be a potential source of antiviral compounds against EBV.

  12. Antioxidant and acetylcholinesterase inhibition properties of Amorpha fruticosa L. and Phytolacca americana L.

    Dimitrina Zh Zheleva-Dimitrova

    2013-01-01

    Full Text Available Background: Amorpha fruticosa L. and Phytolacca americana L. are native plants for North America, but invasive for Central Europe and the Mediterranean areas. Previous investigation reported DPPH radical scavenging activity of A. fruticosa seeds from Mississippi river basin and P. americana berries from Iran. The aim of the present study was to investigate methanol extracts from leaves and fruits of these invasive species growing in Bulgaria for radical scavenging and acetylcholinesterase inhibitory potential. Materials and Methods: Antioxidant activity was investigated using DPPH and ABTS free radicals; FRAP assay and inhibition of lipid peroxidation in linoleic acid system by FTC. Modified Ellman′s colorimetric method was carried out to quantify acetylcholinesterase inhibition potential. In addition, the quantities of total polyphenols, flavonoids, and hydroxycinnamic derivatives were determinated using Folin-Chiocalteu reagent, AlCl 3 , and Na 2 MoO 4 , respectively. Results: The highest concentrations of total polyphenols and flavonoids were found in A. fruticosa leaves (786.70±1.78 mg/g dry extract and 32.19±0.29 mg/g dry extract, respectively. A. fruticosa fruit was found to be the most enriched in total hydroxycinnamic derivatives (153.55±1.11 mg/g dry extract and demonstrated the highest antioxidant activity: DPPH, IC 50 9.83 μg/mL; ABTS, IC 50 2.90 μg/mL; FRAP , 642.95±3.95 μg TE/mg de, and acetylcholinesterase inhibitory activity, 48.86±0.55% (2 mg/mL. Conclusions: Phytolacca americana leaves and Amorpha fruticosa could be useful in therapy of free radical pathologies and neurodegenerative disorders.

  13. Inhibitory Activity of (+-Usnic Acid against Non-Small Cell Lung Cancer Cell Motility.

    Yi Yang

    Full Text Available Lichens are symbiotic organisms that produce various unique chemicals that can be used for pharmaceutical purposes. With the aim of screening new anti-cancer agents that inhibit cancer cell motility, we tested the inhibitory activity of seven lichen species collected from the Romanian Carpathian Mountains against migration and invasion of human lung cancer cells and further investigated the molecular mechanisms underlying their anti-metastatic activity. Among them, Alectoria samentosa, Flavocetraria nivalis, Alectoria ochroleuca, and Usnea florida showed significant inhibitory activity against motility of human lung cancer cells. HPLC results showed that usnic acid is the main compound in these lichens, and (+-usnic acid showed similar inhibitory activity that crude extract have. Mechanistically, β-catenin-mediated TOPFLASH activity and KITENIN-mediated AP-1 activity were decreased by (+-usnic acid treatment in a dose-dependent manner. The quantitative real-time PCR data showed that (+-usnic acid decreased the mRNA level of CD44, Cyclin D1 and c-myc, which are the downstream target genes of both β-catenin/LEF and c-jun/AP-1. Also, Rac1 and RhoA activities were decreased by treatment with (+-usnic acid. Interestingly, higher inhibitory activity for cell invasion was observed when cells were treated with (+-usnic acid and cetuximab. These results implied that (+-usnic acid might have potential activity in inhibition of cancer cell metastasis, and (+-usnic acid could be used for anti-cancer therapy with a distinct mechanisms of action.

  14. Xanthine oxidase inhibitory activities and crystal structures of methoxyflavones from Kaempferia parviflora rhizome.

    Nakao, Kikuyo; Murata, Kazuya; Deguchi, Takahiro; Itoh, Kimihisa; Fujita, Takanori; Higashino, Masayuki; Yoshioka, Yuri; Matsumura, Shin-Ichi; Tanaka, Rika; Shinada, Tetsuro; Ohfune, Yasufumi; Matsuda, Hideaki

    2011-01-01

    Kaempferia parviflora (KP), a Zingiberaceae plant, is used as a folk medicine in Thailand for the treatment of various symptoms, including general pains, colic gastrointestinal disorders, and male impotence. In this study, the inhibitory activities of KP against xanthine oxidase (XOD) were investigated. The extract of KP rhizomes showed more potent inhibitory activity (38% at 500 µg/ml) than those of the other Zingiberaceae plants tested. Ten methoxyflavones were isolated from the KP extract as the major chemical components and their chemical structures were elucidated by X-ray crystallography. The structurally confirmed methoxyflavones were subjected to the XOD inhibitory test. Among them, 3,5,7,4',5'-pentamethoxyflavone and 3',4',5,7-tetramethoxyflavone showed inhibitory activities (IC(50) of 0.9 and >4 mM, respectively) and their modes of inhibition are clarified as competitive/non-competitive mixed type. To the best of our knowledge, this is the first report to present the inhibitory activities of KP, 3,5,7,4',5'-pentamethoxyflavone and 3',4',5,7-tetramethoxyflavone against XOD. PMID:21720029

  15. Effect of Jatropha curcas Peptide Fractions on the Angiotensin I-Converting Enzyme Inhibitory Activity

    Maira R. Segura-Campos

    2013-01-01

    Full Text Available Hypertension is one of the most common worldwide diseases in humans. Angiotensin I-converting enzyme (ACE plays an important role in regulating blood pressure and hypertension. An evaluation was done on the effect of Alcalase hydrolysis of defatted Jatropha curcas kernel meal on ACE inhibitory activity in the resulting hydrolysate and its purified fractions. Alcalase exhibited broad specificity and produced a protein hydrolysate with a 21.35% degree of hydrolysis and 34.87% ACE inhibition. Ultrafiltration of the hydrolysate produced peptide fractions with increased biological activity (24.46–61.41%. Hydrophobic residues contributed substantially to the peptides’ inhibitory potency. The 5–10 and <1 kDa fractions were selected for further fractionation by gel filtration chromatography. ACE inhibitory activity (% ranged from 22.66 to 45.96% with the 5–10 kDa ultrafiltered fraction and from 36.91 to 55.83% with the <1 kDa ultrafiltered fraction. The highest ACE inhibitory activity was observed in F2 ( μg/mL from the 5–10 kDa fraction and F1 ( μg/mL from the <1 kDa fraction. ACE inhibitory fractions from Jatropha kernel have potential applications in alternative hypertension therapies, adding a new application for the Jatropha plant protein fraction and improving the financial viability and sustainability of a Jatropha-based biodiesel industry.

  16. Inhibitory potential of some Romanian medicinal plants against enzymes linked to neurodegenerative diseases and their antioxidant activity

    Gabriela Paun; Elena Neagu; Camelia Albu; Gabriel Lucian Radu

    2015-01-01

    Context: Eryngium planum, Geum urbanum and Cnicus benedictus plants are an endemic botanical from the Romanian used in folk medicine. Objective: The extracts from three Romanian medicinal plants were investigated for their possible neuroprotective potential. Materials and Methods: Within this study, in vitro neuroprotective activity of the extracts of E. planum, G. urbanum, and C. benedictus plants were investigated via inhibition of acetylcholinesterase (AChE) and tyrosinase (TYR). Total con...

  17. Nutritional Composition, α-Glucosidase Inhibitory and Antioxidant Activities of Ophiopogon japonicus Tubers

    Yancui Wang

    2015-01-01

    Full Text Available Ophiopogon japonicus tubers have been widely used as food and traditional Chinese medicine in China. However, their nutritional composition has not been fully reported yet. This study aimed to analyze the nutritional composition of O. japonicus tubers. The α-glucosidase inhibitory and antioxidant activities of the extracts obtained from O. japonicus tubers were also evaluated by in vitro assays. The results indicated that O. japonicus tubers are rich in carbohydrates, proteins, minerals, and amino acids. Among four extracts, the n-butanol fraction (nBF and chloroform/methanol extract (CME of O. japonicus tubers had high amounts of total phenolic and flavonoid contents and exhibited good α-glucosidase inhibitory and antioxidant activities. The α-glucosidase inhibition of nBF was higher than acarbose. Overall, O. japonicus tubers are full of nutritional compounds and have good α-glucosidase inhibitory and antioxidant activities.

  18. Behavioral state-specific inhibitory postsynaptic potentials impinge on cat lumbar motoneurons during active sleep.

    Morales, F R; Boxer, P; Chase, M H

    1987-11-01

    High-gain intracellular records were obtained from lumbar motoneurons in intact, undrugged cats during naturally occurring states of wakefulness, quiet sleep, and active sleep. Spontaneous, discrete, inhibitory postsynaptic potentials (IPSPs) were found to impinge on lumbar motoneurons during all states of sleep and wakefulness. IPSPs which occurred during wakefulness and quiet sleep were of relatively low amplitude and had a low frequency of occurrence. During the state of active sleep there occurred a great increase in inhibitory input. This was the result of the appearance of large-amplitude IPSPs and of an increase in the frequency of low-amplitude IPSPs which were indistinguishable from those recorded during wakefulness and quiet sleep. In addition to a difference in amplitude, the time course of the large IPSPs recorded during active sleep further differentiated them from the smaller IPSPs recorded during wakefulness, quiet sleep, and active sleep; i.e., their rise-time and half-width were of longer duration and their rate-of-rise was significantly faster. We suggest that the large, active sleep-specific IPSPs reflect the activity of a group of inhibitory interneurons which are inactive during wakefulness and quiet sleep and which discharge during active sleep. These as yet unidentified interneurons would then serve as the last link in the brain stem-spinal cord inhibitory system which is responsible for producing muscle atonia during the state of active sleep. PMID:3666087

  19. Biomarkers of oxidative stress and acetylcholinesterase activity in the blood of grass snake (Natrix natrix L. during prehibernation and posthibernation periods

    Jelena Gavric

    2015-06-01

    Full Text Available This work examined the enzymatic (superoxide dismutase-CuZn SOD, catalase-CAT, glutathione peroxidase-GSHPx, glutathione reductase-GR, and the biotransformation phase II enzyme glutathione-S-transferase-GST and nonenzymatic (total glutathione-GSH and lipid peroxides-TBARS concentrations biomarkers of oxidative stress and acetylcholinesterase (AChE activity in the blood of the grass snake (Natrix natrix L. during prehibernation and posthibernation. The animals were collected in October (prehibernation and April (posthibernation at the nature reserve Obedska Bara (OB and industrial region Pancevacki Rit (PR in Serbia. In posthibernation, decreased CAT activity and TBARS concentration in specimens from PR, and decreased GR and AChE activities, and TBARS concentration in specimens from OB were observed, whereas GR and GST activities and GSH concentration were significantly elevated in the specimens from PR. In prehibernation, CAT activity and GSH concentration were increased, while GSH-Px, GR, GST and AChE activities and TBARS concentration were decreased in the specimens from PR when compared to animals from OB. During the posthibernation, the activity of CuZn SOD was decreased, while GST and AChE activities were increased in the specimens from PR when compared to the specimens from OB. These differences represented an adaptive mechanism to oxidative stress induced by tissue reoxygenation during arousal from hibernation and could be modulated by environmental pollution.

  20. Inhibitory Activities of Alkyl Syringates and Related Compounds on Aflatoxin Production

    Tomohiro Furukawa

    2016-06-01

    Full Text Available Inhibitors of aflatoxin production of aflatoxigenic fungi are useful for preventing aflatoxin contamination in crops. As methyl syringate weakly inhibits aflatoxin production, aflatoxin production inhibitory activities of additional alkyl syringates with alkyl chains from ethyl to octyl were examined. Inhibitory activity toward aflatoxin production of Aspergillus flavus became stronger as the length of the alkyl chains on the esters became longer. Pentyl, hexyl, heptyl, and octyl syringates showed strong activity at 0.05 mM. Heptyl and octyl parabens, and octyl gallate also inhibited aflatoxin production as strongly as octyl syringate. Alkyl parabens and alkyl gallates inhibit the complex II activity of the mitochondrial respiration chain; thus, whether alkyl syringates inhibit complex II activity was examined. Inhibitory activities of alkyl syringates toward complex II also became stronger as the length of the alkyl chains increased. The complex II inhibitory activity of octyl syringate was comparable to that of octyl paraben and octyl gallate. These results suggest that alkyl syringates, alkyl parabens, and alkyl gallates, including commonly used food additives, are useful for aflatoxin control.

  1. Inhibitory Activities of Alkyl Syringates and Related Compounds on Aflatoxin Production.

    Furukawa, Tomohiro; Iimura, Kurin; Kimura, Taichi; Yamamoto, Toshiyoshi; Sakuda, Shohei

    2016-01-01

    Inhibitors of aflatoxin production of aflatoxigenic fungi are useful for preventing aflatoxin contamination in crops. As methyl syringate weakly inhibits aflatoxin production, aflatoxin production inhibitory activities of additional alkyl syringates with alkyl chains from ethyl to octyl were examined. Inhibitory activity toward aflatoxin production of Aspergillus flavus became stronger as the length of the alkyl chains on the esters became longer. Pentyl, hexyl, heptyl, and octyl syringates showed strong activity at 0.05 mM. Heptyl and octyl parabens, and octyl gallate also inhibited aflatoxin production as strongly as octyl syringate. Alkyl parabens and alkyl gallates inhibit the complex II activity of the mitochondrial respiration chain; thus, whether alkyl syringates inhibit complex II activity was examined. Inhibitory activities of alkyl syringates toward complex II also became stronger as the length of the alkyl chains increased. The complex II inhibitory activity of octyl syringate was comparable to that of octyl paraben and octyl gallate. These results suggest that alkyl syringates, alkyl parabens, and alkyl gallates, including commonly used food additives, are useful for aflatoxin control. PMID:27338472

  2. Stress-related changes of benzodiazepine binding inhibitory activity (B.B.I.A.) in humans.

    Marazziti, D; Michelini, S; Giannaccini, G; Martini, C; Castrogiovanni, P; Cassano, G B; Lucacchini, A

    1990-01-01

    The presence of benzodiazepine binding inhibitory activity (B.B.I.A.) in sera from 44 psychiatric patients and from 14 healthy volunteers, prompted us to investigate whether or not this activity underwent changes in stressful situations. We measured the inhibitory units (IU) of deproteinized sera of 12 subjects, immediately before and 2 weeks after sitting for a difficult university exam. Our results showed significantly higher IU values (i.e., higher B.B.I.A. concentrations) in the samples taken just before the exam. This preliminary finding clearly suggests the involvement of B.B.I.A. in anxiety mechanisms. PMID:2362542

  3. alpha-Glycosidase inhibitory activity of hexagalloylglucose from the galls of Quercus infectoria.

    Hwang, J K; Kong, T W; Baek, N I; Pyun, Y R

    2000-04-01

    Hexagalloylglucose (3-O-digalloyl-1,2,4,6-tetra-O-galloyl-beta-D- glucose), which was isolated from the methanol extract of the galls of Quercus infectoria, significantly inhibited alpha-glycosidases such as sucrase, maltase and isomaltase. Its inhibitory activity was comparable to acarbose being used as a hypoglycemic agent, while the inhibitory activity on alpha-amylase was approximately 10 times lower than that of acarbose. The results indicate that, when compared to acarbose, hexagalloylglucose might reduce the side effects by reducing inhibition of alpha-amylase. PMID:10821056

  4. Synthesis of Benzophenone Hydrazone Analogs and their DPPH Radical Scavenging and Urease Inhibitory Activates

    Benzophenone hydrazone analogs 1-25 were synthesized and evaluated for antioxidant (DPPH radical scavenging), and urease inhibitory activities. Out of twenty-five analogs, compounds 8, 23, and 1 showed potent free radical scavenging activities with IC50 values 19.45 ± 1.25, 21.72 ± 1.49, and 26.0 ± 0.52 μM, respectively, while compound 8 (IC50 = 36.36 ± 0.94 μ M), and 15 (IC50 = 55.5 ± 0.69 μ M), showed good to moderate urease inhibitory potential. (author)

  5. Ascorbyl palmitate-loaded chitosan nanoparticles: characteristic and polyphenol oxidase inhibitory activity.

    Kim, Mi Kyung; Lee, Ji-Soo; Kim, Kwang Yup; Lee, Hyeon Gyu

    2013-03-01

    The aim of this study was to produce ascorbyl palmitate (AP)-loaded nanoparticles in order to inhibit polyphenol oxidase (PPO) in bananas. AP-loaded chitosan nanoparticles were prepared using acetic acid and citric acid (denoted as CS/AA and CS/CA nanoparticles, respectively). As the initial AP concentration increases, the particle size significantly decreases, and the zeta potential, entrapment and loading efficiency significantly increases. The PPO inhibitory activity of AP was effectively improved when AP was nano-encapsulated by chitosan compared to no encapsulation. These results suggest that chitosan nano-encapsulation can be used to enhance the PPO inhibitory activity of AP. PMID:23247266

  6. Extracellular melanogenesis inhibitory activity and the structure-activity relationships of ugonins from Helminthostachys zeylanica roots.

    Yamauchi, Kosei; Mitsunaga, Tohru; Itakura, Yuki; Batubara, Irmanida

    2015-07-01

    Ugonin J, K, and L, which are luteolin derivatives, were isolated from Helminthostachys zeylanica roots by a series of chromatographic separations of a 50% ethanol/water extract. They were identified using nuclear magnetic resonance (NMR), ultraviolet (UV) spectra, and ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC-TOF-MS). In this study, the intra and extracellular melanogenic activity of the ugonins were determined using B16 melanoma cells. The results showed that ugonin J at 12.5, 25, and 50μM reduced extracellular melanin contents to 75, 16, and 14%, respectively, compared to the control. This indicates that ugonin J showed a stronger activity than arbutin, used as the positive control. Moreover, ugonin K showed a more potent inhibition with 19, 8, and 9% extracellular melanin reduction at the same concentrations, than that shown by ugonin J. In contrast, ugonin L did not inhibit intra- or extracellular melanogenic activity. Furthermore, in order to investigate the structure-activity relationships of the ugonins, the intra- and extracellular melanogenic activity of luteolin, methylluteolin, quercetin, eriodictyol, apigenin, and chrysin were determined. Consequently, it was suggested that the catechol and flavone skeleton of ugonin K is essential for the extracellular melanogenic inhibitory activity, and the low polarity substituent groups on the A ring of ugonin K may increase the activity. PMID:25979512

  7. Ultrasonic extraction of polysaccharides from Laminaria japonica and their antioxidative and glycosidase inhibitory activities

    Wan, Peng; Yang, Xiaoman; Cai, Bingna; Chen, Hua; Sun, Huili; Chen, Deke; Pan, Jianyu

    2015-08-01

    In the present study, ultrasonic extraction technique (UET) is used to improve the yield of polysaccharides from Laminaria japonica (LJPs). And their antioxidative as well as glycosidase inhibitory activities are investigated. Box-Behnken design (BBD) combined with response surface methodology (RSM) is applied to optimize ultrasonic extraction for polysaccharides. The optimized conditions are obtained as extraction time at 54 min, ultrasonic power at 1050 W, extraction temperature at 80°C and ratio of material to solvent at 1:50 (g mL-1). Under these optimal ultrasonic extraction conditions, an actual experimental yield (5.75% ± 0.3%) is close to the predicted result (5.67%) with no significant difference ( P > 0.05). Vitro antioxidative and glycosidase inhibitory activities tests indicate that the crude polysaccharides (LJP) and two major ethanol precipitated fractions (LJP1 and LJP2) are in a concentration-dependent manner. LJP2 (30%-60% ethanol precipitated polysaccharides) possesses the strongest α-glucosidase inhibitory activity and moderate scavenging activity against hydroxyl radicals (66.09% ± 2.19%, 3.0 mg mL-1). Also, the inhibitory activity against α-glucosidase (59.08% ± 3.79%, 5.0 mg mL-1) is close to that of acarbose (63.99% ± 3.27%, 5.0 mg mL-1). LJP1 (30% ethanol precipitated polysaccharides) exhibits the strongest scavenging activity against hydroxyl radicals (99.80% ± 0.00%, 3.0 mg mL-1) and moderate α-glucosidase inhibitory activity (47.76% ± 1.92%, 5.0 mg mL-1). LJP shows the most remarkable DPPH scavenging activity (66.20% ± 0.11%, 5.0 mg mL-1) but weakest α-glucosidase inhibitory activity (37.77% ± 1.30%, 5.0 mg mL-1). However, all these LJPs exert weak inhibitory effects against α-amylase. These results show that UET is an effective method for extracting bioactive polysaccharides from seaweed materials. LJP1 and LJP2 can be developed as a potential ingredient in hypoglycemic agents or functional food for the management of

  8. Inhibitory effects of cefotaxime on the activity of mushroom tyrosinase.

    Hu, Yong-Hua; Zhuang, Jiang-Xing; Yu, Feng; Cui, Yi; Yu, Wen-Wen; Yan, Chong-Ling; Chen, Qing-Xi

    2016-04-01

    Tyrosinase (EC 1.14.18.1) catalyzes both the hydroxylation of tyrosine into o-diphenols and the oxidation of o-diphenols into o-quinones that form brown or black pigments. In the present paper, cefotaxime, a cephalosporin antibacterial drug, was tested as an inhibitor of tyrosinase. The results show that cefotaxime inhibits both the monophenolase and diphenolase activities of tyrosinase. For the monophenolase activity, cefotaxime increased the lag time and decreased the steady-state activity with an IC50 of 3.2 mM. For the diphenolase activity, the inhibition by cefotaxime is reversible and mix-I type with an IC50 of 0.14 mM. The inhibition constants (KI and KIS) were determined to be 0.14 and 0.36 mM, respectively. The molecular mechanism of inhibition of tyrosinase by cefotaxime was determined by fluorescence quenching and molecular docking. The results demonstrated that cefotaxime was a static quencher of tyrosinase and that cefotaxime could dock favorably in the active site of tyrosinase. This research may offer a lead for designing and synthesizing novel and effective tyrosinase inhibitors in the future. PMID:26342770

  9. Honey shows potent inhibitory activity against the bovine testes hyaluronidase.

    Kolayli, Sevgi; Sahin, Huseyin; Can, Zehra; Yildiz, Oktay; Sahin, Kübra

    2016-08-01

    The purpose of this study was to investigate the anti-hyaluronidase activities of honeys from different botanical origins honeys in order to determine their anti-inflammatory properties. The total phenolic contents, total flavonoids and total tannin levels of six types of honey, chestnut, oak, heather, pine, buckwheat and mixed blossom, were determined. Concentration-related inhibition values were tested turbidimetrically on bovine testis hyaluronidase (BTHase) as IC50 (mg/mL). All honeys exhibited various concentration-dependent degrees of inhibition against BTHase. Inhibition values varied significantly depending on honeys' levels of phenolic contents, flavonoid and tannin. The honeys with the highest anti-hyaluronidase activity were oak, chestnut and heather. In conclusion, polyphenol-rich honeys have high anti-hyaluronidase activity, and these honeys have high protective and complementary potential against hyaluronidase-induced anti-inflammatory failures. PMID:26076195

  10. Detection of Carbofuran with Immobilized Acetylcholinesterase Based on Carbon Nano tubes-Chitosan Modified Electrode

    A sensitive and stable enzyme biosensor based on efficient immobilization of acetylcholinesterase (AChE) to MWNTs-modified glassy carbon electrode (GCE) with chitosan (CS) by layer-by-layer (LBL) technique for rapid determination of carbofuran has been devised. According to the inhibitory effect of carbamate pesticide on the enzymatic activity of AChE, we use carbofuran as a model pesticide. The inhibitory effect of carbofuran on the biosensor was proportional to concentration of carbofuran in the range from 10-10  g/L to 10-3 g/L with a detection limit of 10-12 g/L. This biosensor is a promising new method for pesticide analysis

  11. Competition between activating and inhibitory processes in photobiology

    Friedmann, Harry; Lubart, Rachel

    1996-01-01

    We discuss light-induced stimulation and inhibition of biological activity by means of three types of competing processes. In the visible region, these competing processes are the formation by photosensitization of reactive oxygen species (ROS) which stimulate the redox activity of the respiratory chain (RC) on the one hand, and intramolecular electronic- vibrational energy transfer from an endogenous photosensitizer to an enzyme of the RC, thereby bringing this enzyme into an inactive configuration and paralyzing the RC, on the other hand. Moreover, there is competition between stimulation of the redox activity of the RC by the ROS and a slower process where the enzymes of the RC react with the ROS, again paralyzing the RC. This paralysis of the RC plays a dominant role in photodynamic therapy, where exogenous photosensitizers together with a sufficiently large visible light-energy dose lead to overproduction of ROS. Finally, in the far-red region, there is competition between reactivation of the ATPase ion pumps in the cell membrane and inhibition of the enzymes in the RC as a result of vibrational overtone excitation. Photobioactivation is shown to lead to enhanced transient Ca2+ concentration increase (calcium oscillations) in the cytosol, thereby triggering further biological activity such as afflux of intercellular messengers which open gated ion channels in neighboring cells, producing calcium waves. Addition of ROS scavengers or quenchers such as SOD in the presence of catalase neutralizes photobiomodulation induced by visible light.

  12. Screening of some Yemeni medicinal plants for inhibitory activity against peptidases.

    Alasbahi, R; Melzig, M F

    2008-01-01

    Extracts of different polarities (dichloromethane, methanol, and aqueous extracts) from 5 Yemeni medicinal plants (Aspilia helianthoides, leaves; Ceropegia rupicola, whole plant; Kniphofia sumarae, whole plant; Pavetta longiflora, leaves; and Plectranthus cf barbatus, leaves) were screened for their inhibitory effects against angiotensin converting enzyme (ACE), neutral endopeptidase (NEP), and aminopeptidase N (APN) activities. Four extracts (methanol extracts of Ceropegia rupicola, Kniphofia sumarae, and Plectranthus cf barbatus, and the aqueous extract of Pavetta longiflora) were found able to inhibit the enzymatic activity of NEP. Significant reduction in the activity of NEP (p Ceropegia rupicola with IC50 of 111 microg/ml. Only the methanolic extract of Aspilia helianthoides was found to exhibit inhibitory effect against the ACE activity with IC50 = 133 microg/ml. None of the tested plant extracts was found active against the aminopeptidase N activity. PMID:18271311

  13. Nickel in Soil Modifies Sensitivity to Diazinon Measured by the Activity of Acetylcholinesterase, Catalase, and Glutathione S-Transferase in Earthworm Eisenia fetida

    Agnieszka Zawisza-Raszka

    2013-01-01

    Full Text Available Nickel in typical soils is present in a very low concentration, but in the contaminated soils it occurs in locally elevated concentrations. The aim of this study was to examine the effect of nickel in the concentrations of 300 (very high, close to LOEC for reproduction and 900 (extremely high, close to LOEC for mortality mg/kg dry soil on the life history and acetylcholinesterase, catalase, and glutathione S-transferase activities in earthworm Eisenia fetida and to establish how nickel modifies the sensitivity to organophosphorous pesticide—diazinon. Cocoons production and juveniles’ number were significantly lower only in groups exposed to Ni in the concentration of 900 mg/kg dry soil for two months. Diazinon administration diminished the AChE activity in the GI tract and in the body wall. The interaction between diazinon and nickel was observed, and, in consequence, the AChE activity after the pesticide treatment was similar to controls in worms preexposed to nickel. Both pesticide administration and exposure to nickel caused an increase in the GST activity in examined organs and CAT activity in body wall. Both biometric and development data and simple enzymatic analysis, especially the AChE and GST, show a Ni pretreatment effect on the subsequent susceptibility to pesticide.

  14. Intraperitoneal Exposure to Nano/Microparticles of Fullerene (C60) Increases Acetylcholinesterase Activity and Lipid Peroxidation in Adult Zebrafish (Danio rerio) Brain

    Dal Forno, Gonzalo Ogliari; Kist, Luiza Wilges; de Azevedo, Mariana Barbieri; Fritsch, Rachel Seemann; Pereira, Talita Carneiro Brandão; Britto, Roberta Socoowski; Guterres, Sílvia Stanisçuaski; Külkamp-Guerreiro, Irene Clemes; Bonan, Carla Denise; Monserrat, José María; Bogo, Maurício Reis

    2013-01-01

    Even though technologies involving nano/microparticles have great potential, it is crucial to determine possible toxicity of these technological products before extensive use. Fullerenes C60 are nanomaterials with unique physicochemical and biological properties that are important for the development of many technological applications. The aim of this study was to evaluate the consequences of nonphotoexcited fullerene C60 exposure in brain acetylcholinesterase expression and activity, antioxidant responses, and oxidative damage using adult zebrafish as an animal model. None of the doses tested (7.5, 15, and 30 mg/kg) altered AChE activity, antioxidant responses, and oxidative damage when zebrafish were exposed to nonphotoexcited C60 nano/microparticles during 6 and 12 hours. However, adult zebrafish exposed to the 30 mg/kg dose for 24 hours have shown enhanced AChE activity and augmented lipid peroxidation (TBARS assays) in brain. In addition, the up-regulation of brain AChE activity was neither related to the transcriptional control (RT-qPCR analysis) nor to the direct action of nonphotoexcited C60 nano/microparticles on the protein (in vitro results) but probably involved a posttranscriptional or posttranslational modulation of this enzymatic activity. Taken together these findings provided further evidence of toxic effects on brain after C60 exposure. PMID:23865059

  15. Bioactive diterpenoids from Trigonostemon chinensis: Structures, NO inhibitory activities, and interactions with iNOS.

    Xu, Jing; Peng, Maoqin; Sun, Xiaocong; Liu, Xingyu; Tong, Ling; Su, Guochen; Ohizumi, Yasushi; Lee, Dongho; Guo, Yuanqiang

    2016-10-01

    A phytochemical investigation to obtain new NO inhibitors led to the isolation of two new (1 and 2) and four known (3-6) diterpenoids from Trigonostemon chinensis. Their structures were elucidated on the basis of extensive 1D and 2D NMR spectroscopic data analyses, and the absolute configurations of new compounds were established by experimental and calculated ECD spectra. The inhibitory activities on lipopolysaccharide-induced NO production in murine microglial BV-2 cells of these diterpenoids were evaluated, and all of the compounds showed inhibitory effects. The interactions of bioactive compounds with iNOS protein were also studied by molecular docking. PMID:27570243

  16. ACE inhibitory activity of pangasius catfish (Pangasius sutchi) skin and bone gelatin hydrolysate

    Mahmoodani, Fatemeh; Ghassem, Masomeh; Babji, Abdul Salam; Yusop, Salma Mohamad; Khosrokhavar, Roya

    2012-01-01

    Skin and bone gelatins of pangasius catfish (Pangasius sutchi) were hydrolyzed with alcalase to isolate Angiotensin Converting Enzyme (ACE) inhibitory peptides. Samples with the highest degree of hydrolysis (DH) were separated into different fractions with molecular weight cut-off (MWCO) sizes of 10, 3 and 1 kDa, respectively and assayed for ACE inhibitory activity. Skin and bone gelatins had highest DH of 64.87 and 68.48 % after 2 and 1 h incubation, respectively. Results from this study ind...

  17. Antioxidant Activities and Tyrosinase Inhibitory Effects of Different Extracts from Pleurotus ostreatus Fruiting Bodies

    Alam, Nuhu; Yoon, Ki Nam; Lee, Kyung Rim; Shin, Pyung Gyun; Cheong, Jong Chun; Yoo, Young Bok; Shim, Ja Mi; Lee, Min Woong; Lee, U Youn; Lee, Tae Soo

    2010-01-01

    We evaluated the antioxidant activity and tyrosinase inhibitory effects of Pleurotus ostreatus fruiting bodies extracted with acetone, methanol, and hot water. The antioxidant activities were tested against β-carotene-linoleic acid, reducing power, 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity, and ferrous chelating ability. Furthermore, phenolic acid and flavonoid contents were also analyzed. The methanol extract showed the strongest β-carotene-linoleic acid inhibition as co...

  18. Tyrosinase Inhibitory Effects and Antioxidative Activities of Saponins from Xanthoceras Sorbifolia Nutshell

    Zhang, Hongmei; Zhou, Quancheng

    2013-01-01

    Certain saponins are bioactive compounds with anticancer, antivirus and antioxidant activities. This paper discussed inhibitory effects of saponins from Xanthoceras Sorbifolia on tyrosinase, through the research of the rate of tyrosinase catalyzed L-DOPA oxidation. The inhibition rate of tyrosinase activity presented non-linear changes with the saponins concentration. The rate reached 52.0% when the saponins concentration was 0.96 mg/ml. Antioxidant activities of saponins from Xanthoceras Sor...

  19. Angiotensin I-Converting Enzyme (ACE Inhibitory Activity and ACE Inhibitory Peptides of Salmon (Salmo salar Protein Hydrolysates Obtained by Human and Porcine Gastrointestinal Enzymes

    Małgorzata Darewicz

    2014-08-01

    Full Text Available The objectives of the present study were two-fold: first, to detect whether salmon protein fractions possess angiotensin I-converting enzyme (ACE inhibitory properties and whether salmon proteins can release ACE inhibitory peptides during a sequential in vitro hydrolysis (with commercial porcine enzymes and ex vivo digestion (with human gastrointestinal enzymes. Secondly, to evaluate the ACE inhibitory activity of generated hydrolysates. A two-step ex vivo and in vitro model digestion was performed to simulate the human digestion process. Salmon proteins were degraded more efficiently by porcine enzymes than by human gastrointestinal juices and sarcoplasmic proteins were digested/hydrolyzed more easily than myofibrillar proteins. The ex vivo digested myofibrillar and sarcoplasmic duodenal samples showed IC50 values (concentration required to decrease the ACE activity by 50% of 1.06 and 2.16 mg/mL, respectively. The in vitro hydrolyzed myofibrillar and sarcoplasmic samples showed IC50 values of 0.91 and 1.04 mg/mL, respectively. Based on the results of in silico studies, it was possible to identify 9 peptides of the ex vivo hydrolysates and 7 peptides of the in vitro hydrolysates of salmon proteins of 11 selected peptides. In both types of salmon hydrolysates, ACE-inhibitory peptides IW, IY, TVY and VW were identified. In the in vitro salmon protein hydrolysates an ACE-inhibitory peptides VPW and VY were also detected, while ACE-inhibitory peptides ALPHA, IVY and IWHHT were identified in the hydrolysates generated with ex vivo digestion. In our studies, we documented ACE inhibitory in vitro effects of salmon protein hydrolysates obtained by human and as well as porcine gastrointestinal enzymes.

  20. Activity and expression of acetylcholinesterase in PC12 cells exposed to intermittent 1.8 GHz 217-GSM mobile phone signal.

    Valbonesi, Paola; Franzellitti, Silvia; Bersani, Ferdinando; Contin, Andrea; Fabbri, Elena

    2016-01-01

    Purpose Due to its role in learning, memory and in many neurodegenerative diseases, acetylcholinesterase (AChE) represents an interesting endpoint to assess possible targets of exposure to radiofrequency electromagnetic fields (RF-EMF) generated by mobile phones. We investigated possible alterations of enzymatic activity, gene and protein expression of AChE in neuronal-like cells exposed to a 1.8 GHz Global System for Mobile Communication (GSM) modulated signal (217-GSM). Materials and methods Rat PC12 cells were exposed for 24 h to 1.8 GHz 217-GSM signal. Specific adsorption rate (SAR) was 2 W/kg. AChE enzyme activity was assessed spectrophotometrically by Ellman's method, mRNA expression level was evaluated by real time polymerase chain reaction, and protein expression was assessed by Western blotting. Results AChE enzymatic activity increased of 1.4-fold in PC12 cells exposed to 217-GSM signal for 24 h, whilst AChE transcriptional or translational pathways were not affected. Conclusion Our results provide the first evidence of effects on AChE activity after in vitro exposure of mammalian cells to the RF-EMF generated by GSM mobile phones, at the SAR value 2 W/kg. The obtained evidence promotes further investigations on AChE as a possible target of RF-EMF and confirm the ability of 1.8 GHz 217-GSM signal to induce biological effects in different mammalian cells. PMID:26630175

  1. Chemical Evidence for Potent Xanthine Oxidase Inhibitory Activity of Ethyl Acetate Extract of Citrus aurantium L. Dried Immature Fruits

    Kun Liu

    2016-03-01

    Full Text Available Xanthine oxidase is a key enzyme which can catalyze hypoxanthine and xanthine to uric acid causing hyperuricemia in humans. Xanthine oxidase inhibitory activities of 24 organic extracts of four species belonging to Citrus genus of the family Rutaceae were assayed in vitro. Since the ethyl acetate extract of C. aurantium dried immature fruits showed the highest xanthine oxidase inhibitory activity, chemical evidence for the potent inhibitory activity was clarified on the basis of structure identification of the active constituents. Five flavanones and two polymethoxyflavones were isolated and evaluated for inhibitory activity against xanthine oxidase in vitro. Of the compounds, hesperetin showed more potent inhibitory activity with an IC50 value of 16.48 μM. For the first time, this study provides a rational basis for the use of C. aurantium dried immature fruits against hyperuricemia.

  2. Chemical Evidence for Potent Xanthine Oxidase Inhibitory Activity of Ethyl Acetate Extract of Citrus aurantium L. Dried Immature Fruits.

    Liu, Kun; Wang, Wei; Guo, Bing-Hua; Gao, Hua; Liu, Yang; Liu, Xiao-Hong; Yao, Hui-Li; Cheng, Kun

    2016-01-01

    Xanthine oxidase is a key enzyme which can catalyze hypoxanthine and xanthine to uric acid causing hyperuricemia in humans. Xanthine oxidase inhibitory activities of 24 organic extracts of four species belonging to Citrus genus of the family Rutaceae were assayed in vitro. Since the ethyl acetate extract of C. aurantium dried immature fruits showed the highest xanthine oxidase inhibitory activity, chemical evidence for the potent inhibitory activity was clarified on the basis of structure identification of the active constituents. Five flavanones and two polymethoxyflavones were isolated and evaluated for inhibitory activity against xanthine oxidase in vitro. Of the compounds, hesperetin showed more potent inhibitory activity with an IC50 value of 16.48 μM. For the first time, this study provides a rational basis for the use of C. aurantium dried immature fruits against hyperuricemia. PMID:26950105

  3. In vivo hypotensive effect and in vitro inhibitory activity of some Cyperaceae species

    Monica Lacerda Lopes Martins

    2013-12-01

    Full Text Available In 1820, French naturalist August Saint Hillaire, during a visit in Espírito Santo (ES, a state in southeastern Brazil, reported a popular use of Cyperaceae species as antidote to snake bites. The plant may even have a hypotensive effect, though it was never properly researched. The in vitro inhibitory of the angiotensin converting enzyme (ACE activity of eigth ethanolic extracts of Cyperaceae was evaluated by colorimetric assay. Total phenolic and flavonoids were determined using colorimetric assay. The hypotensive effect of the active specie (Rhychonospora exaltata, ERE and the in vivo ACE assay was measured in vivo using male Wistar Kyoto (ERE, 0.01-100mg/kg, with acetylcholine (ACh as positive control (5 µg/kg, i.v.. The evaluation of ACE in vivo inhibitory effect was performed comparing the mean arterial pressure before and after ERE (10 mg/kg in animals which received injection of angiotensin I (ANG I; 0,03, 03 and 300 µg/kg, i.v.. Captopril (30 mg/kg was used as positive control. Bulbostylis capillaris (86.89 ± 15.20% and ERE (74.89 ± 11.95%, ERE were considered active in the in vitro ACE inhibition assay, at 100 µg/mL concentration. ACh lead to a hypotensive effect before and after ERE's curve (-40±5% and -41±3%. ERE showed a dose-dependent hypotensive effect and a in vivo ACE inhibitory effect. Cyperaceae species showed an inhibitory activity of ACE, in vitro, as well as high content of total phenolic and flavonoids. ERE exhibited an inhibitory effect on both in vitro and in vivo ACE. The selection of species used in popular medicine as antidotes, along with the in vitro assay of ACE inhibition, might be a biomonitoring method for the screening of new medicinal plants with hypotensive properties.

  4. Secondary Metabolites Produced by an Endophytic Fungus Pestalotiopsis sydowiana and Their 20S Proteasome Inhibitory Activities.

    Xia, Xuekui; Kim, Soonok; Liu, Changheng; Shim, Sang Hee

    2016-01-01

    Fungal endophytes have attracted attention due to their functional diversity. Secondary metabolites produced by Pestalotiopsis sydowiana from a halophyte, Phragmites communis Trinus, were investigated. Eleven compounds, including four penicillide derivatives (1-4) and seven α-pyrone analogues (5-10) were isolated from cultures of P. sydowiana. The compounds were identified based on spectroscopic data. The inhibitory activities against the 20S proteasome were evaluated. Compounds 1-3, 5, and 9-10 showed modest proteasome inhibition activities, while compound 8 showed strong activity with an IC50 of 1.2 ± 0.3 μM. This is the first study on the secondary metabolites produced by P. sydowiana and their proteasome inhibitory activities. The endophytic fungus P. sydowiana might be a good resource for proteasome inhibitors. PMID:27447600

  5. Phenolic constituents from the heartwood of Artocapus altilis and their tyrosinase inhibitory activity.

    Nguyen, Mai Ha Khoa; Nguyen, Hai Xuan; Nguyen, Mai Thanh Thi; Nguyen, Nhan Trung

    2012-02-01

    From the MeOH extract of the heartwood of Artocapus altilis, thirteen phenolic compounds have been isolated, namely curcumin (1), desmethoxycurcumin (2), retrodihydrochalcone (3), apigenin (4), tangeretin (5), nobiletin (6), O-methyldehydrodieugenol (7), dehydrodieugenol (8), beta-hydroxypropiovanillone (9), p-coumaric acid (10), p-hydroxybenzaldehyde (11), vanillin (12), and vanillic acid (13). This is the first report on the presence of these compounds in the heartwood of A. altilis. Compounds 1, 2, and 10 showed more potent tyrosinase inhibitory activities, with IC50 values ranging from 2.3 to 42.0 microM, than the positive control kojic acid (IC50, 44.6 microM). The most active compound, p-coumaric acid (10) (IC50, 2.3 microM), was 22 times more active in tyrosinase inhibitory activity than kojic acid. PMID:22474950

  6. Hyaluronidase and collagenase inhibitory activities of the herbal formulation Triphala guggulu

    Venil N Sumantran; Asavari A Kulkarni; Abhay Harsulkar; Asmita Wele; Soumya J Koppikar; Rucha Chandwaskar; Vishakha Gaire; Madhuri Dalvi; Ulhas V Wagh

    2007-06-01

    Myrrh (guggulu) oleoresin from the Commiphora mukul tree is an important component of antiarthritic drugs in Ayurvedic medicine. Clinical data suggest that elevated levels of hyaluronidase and collagenase type 2 enzymes contribute significantly to cartilage degradation. Triphala guggulu (TG) is a guggulu-based formulation used for the treatment of arthritis. We assessed the chondroprotective potential of TG by examining its effects on the activities of pure hyaluronidase and collagenase type 2 enzymes. Triphala shodith guggulu (TSG), an intermediate in the production of TG, was also examined. A spectrophotometric method was used to assay Hyaluronidase activity, and to detect potential Hyaluronidase inhibitors. Aqueous and hydro-alcoholic extracts of TSG showed weak but dose-dependent inhibition of hyaluronidase activity. In contrast, the TG formulation was 50 times more potent than the TSG extract with respect to hyaluronidase inhibitory activity. A validated X-ray film-based assay was used to measure the gelatinase activity of pure collagenase type 2. Hydro-alcoholic extracts of the TG formulation were 4 times more potent than TSG with respect to collagenase inhibitory activity. Components of Triphala were also evaluated for their inhibitory activities on hyaluronidase and collagenase. This is the first report to show that the T2 component of Triphala (T. chebula) is a highly potent hyaluronidase and collagenase inhibitor. Thus, the TG formulation inhibits two major enzymes that can degrade cartilage matrix. Our study provides the first in vitro preclinical evidence of the chondroprotective properties of TG.

  7. Hypocholesterolemic Effect and In Vitro Pancreatic Lipase Inhibitory Activity of an Opuntia ficus-indica Extract

    Eduardo Padilla-Camberos; Jose Miguel Flores-Fernandez; Ofelia Fernandez-Flores; Yanet Gutierrez-Mercado; Joel Carmona-de la Luz; Fabiola Sandoval-Salas; Carlos Mendez-Carreto; Kirk Allen

    2015-01-01

    Cholesterol control is fundamental for prevention of cardiovascular disorders. In this work, the hypocholesterolemic activity of an aqueous Opuntia ficus-indica extract (AOE) was tested in triton-induced mice. The inhibitory activity on pancreatic lipase enzyme was evaluated in vitro by the same extract. Furthermore, polyphenol content of the extract was evaluated. Hypercholesterolemia was induced in three groups of mice by intraperitoneal administration of Triton WR-1339. After induction of ...

  8. α-GLUCOSIDASE AND α -AMYLASE INHIBITORY ACTIVITIES OF RAPHANUS SATIVUS LINN.

    R. Vadivelan et al

    2012-01-01

    Herbal medicine has been used for many years by different cultures around the world for the treatment of diabetes. There has been an enormous interest in the development of alternative medicines for type 2 diabetes, specifically screening for phytochemicals with the ability to delay or prevent glucose absorption. The goal of the present study is to evaluate the invitro antidiabetic activity of Raphanus sativus ethanolic extract and fractions by α-glucosidase and α -amylase inhibitory activity...

  9. INHIBITORY ACTIVITY OF FLAVONOIDS ON THE LENS ALDOSE REDUCTASE OF HEALTHY AND DIABETIC RATS

    M.T. Goodarzi; Zal, F; M. Malakooti; M. R. Safari S. Sadeghian

    2006-01-01

    Aldose reductase is a critical enzyme in the polyol pathway that plays an important role in diabetes mellitus. Inhibition of the activity of this enzyme can prevent cataract in diabetic patients’lenses. In this study the inhibitory effect of two flavonoids, quercetin and naringin, in the activity of aldose reductase in streptozotocin-induced diabetic and healthy rats were investigated. Thirty male rats were divided in six groups. The first, second and third group were healthy rats that receiv...

  10. Antioxidant, Iron Chelating and Tyrosinase Inhibitory Activities of Extracts from Talinum triangulare Leach Stem

    Ana Paula Oliveira Amorim; Márcia Cristina Campos de Oliveira; Thiago de Azevedo Amorim; Aurea Echevarria

    2013-01-01

    The aim of this work is to evaluate the antioxidant activity against the radical species DPPH, the reducing capacity against Fe II ions, and the inhibitory activity on the tyrosinase enzyme of the T. triangulare. Hydromethanolic crude extract provided two fractions after the liquid/liquid partition with chloroform. The Folin-Ciocalteu method determined the total phenolic content of the crude extract (CE) and the hydromethanolic fraction (Fraction 1), resulting in a concentration of 0.5853 g/1...

  11. Biological evaluation of synthetic α,β-unsaturated carbonyl based cyclohexanone derivatives as neuroprotective novel inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation.

    Zha, Gao-Feng; Zhang, Cheng-Pan; Qin, Hua-Li; Jantan, Ibrahim; Sher, Muhammad; Amjad, Muhammad Wahab; Hussain, Muhammad Ajaz; Hussain, Zahid; Bukhari, Syed Nasir Abbas

    2016-05-15

    A series of new α,β-unsaturated carbonyl-based cyclohexanone derivatives was synthesized by simple condensation method and all compounds were characterized by using various spectroscopic techniques. New compounds were evaluated for their effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These compounds were also screened for in vitro cytotoxicity and for inhibitory activity for self-induced Aβ1-42 aggregation. The effect of these compounds against amyloid β-induced cytotoxicity was also investigated. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against AChE and self-induced Aβ1-42 aggregation. The compound 3o exhibited best AChE (IC50=0.037μM) inhibitory potential. Furthermore, compound 3o disassembled the Aβ fibrils produced by self-induced Aβ aggregation by 76.6%. Compounds containing N-methyl-4-piperidone linker, showed high acetylcholinesterase and self-induced Aβ aggregation inhibitory activities as compared to reference drug donepezil. The pre-treatment of cells with synthetic compounds protected them against Aβ-induced cell death by up to 92%. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment and our study suggest the cyclohexanone derivatives as promising new inhibitors for AChE and BuChE, potentially useful to treat neurodegenerative diseases. PMID:27083471

  12. Flavanone glycosides as acetylcholinesterase inhibitors: Computational and experimental evidence

    Remya, C.; K V Dileep; I Tintu; Variyar, E. J.; Sadasivan, C.

    2014-01-01

    Acetylcholinesterase hydrolyzes the neurotransmitter called acetylcholine and is crucially involved in the regulation of neurotransmission. One of the observable facts in the neurodegenerative disorders like Alzheimer′s disease is the decrease in the level of acetylcholine. Available drugs that are used for the treatment of Alzheimer′s disease are primarily acetylcholinesterase inhibitors with multiple activities. They maintain the level of acetylcholine in the brain by inhibiting the acetylc...

  13. Highly Sensitive and Selective Immuno-capture/Electrochemical Assay of Acetylcholinesterase Activity in Red Blood Cells: A Biomarker of Exposure to Organophosphorus Pesticides and Nerve Agents

    Chen, Aiqiong; Du, Dan; Lin, Yuehe

    2012-02-09

    Acetylcholinesterase (AChE) enzyme activity in red blood cells (RBCs) is a useful biomarker for biomonitoring of exposures to organophosphorus (OP) pesticides and chemical nerve agents. In this paper, we reported a new method for AChE activity assay based on selective immuno-capture of AChE from biological samples followed by enzyme activity assay of captured AChE using a disposable electrochemical sensor. The electrochemical sensor is based on multiwalled carbon nanotubes-gold nanocomposites (MWCNTs-Au) modified screen printed carbon electrode (SPCE). Upon the completion of immunoreaction, the target AChE (including active and inhibited) is captured onto the electrode surface and followed by an electrochemical detection of enzymatic activity in the presence of acetylthiocholine. A linear response is obtained over standard AChE concentration range from 0.1 to 10 nM. To demonstrate the capability of this new biomonitoring method, AChE solutions dosed with different concentration of paraoxon were used to validate the new AChE assay method. AChE inhibition in OP dosed solutions was proportional to its concentration from 0.2 to 50 nM. The new AChE activity assay method for biomonitoring of OP exposure was further validated with in-vitro paraoxon-dosed RBC samples. The established electrochemical sensing platform for AChE activity assay not only avoids the problem of overlapping substrate specificity with esterases by using selective antibody, but also eliminates potential interference from other electroactive species in biological samples. It offers a new approach for sensitive, selective, and rapid AChE activity assay for biomonitoring of exposures to OPs.

  14. Antioxidant/lipoxygenase inhibitory activities and chemical compositions of selected essential oils.

    Wei, Alfreda; Shibamoto, Takayuki

    2010-06-23

    Twenty-five essential oils were tested for antioxidant activities using a conjugated diene assay, the aldehyde/carboxylic acid assay, the DPPH free radical scavenging assay, and the malonaldehyde/gas chromatography (MA/GC) assay. They were also tested for lipoxygenase inhibitory activities using the lipoxygenase inhibitor-screening assay. Thyme oil exhibited the greatest antioxidant effect in all assays (80-100%) except in the DPPH assay (60%). Clove leaf oil showed activities comparable to those of thyme oil (53-100%). Cinnamon leaf oil showed strong activities in the aldehyde/carboxylic acid assay (100%) and DPPH assay (84%), but only moderate activities in the conjugated diene assay (24%) and MA/GC assay (48%). Basil oil exhibited a strong effect in the DPPH assay (86%) and moderate activities in the MA/GC assay (35%). Bergamot oil exhibited 100% antioxidant activity in the aldehyde/carboxylic acid assay. Eucalyptus and chamomile oils showed appreciable activities only in the conjugated diene assay. Bitter orange oil exhibited moderate antioxidant activity (53%) only in the MA/GC assay. Aloe vera oil exhibited the greatest lipoxygenase inhibitory activity (96%), followed by thyme oil (86%) and bergamot oil (85%) at a concentration of 0.5 microg/mL. Chamomile oil showed slight lipoxygenase inhibitory activity at 0.5 microg/mL but strong lipoxygenase inducing activity at 5 microg/mL (-123%). Thyme and clove leaf oils contained high levels of thymol (23%) and eugenol (77%), respectively, as a principal of the antioxidant activity. The results obtained in the present study suggest that some essential oils possess strong medicinal activities, which can be utilized for treatment of certain diseases. PMID:20499917

  15. Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

    Čolović, Mirjana B; Krstić, Danijela Z; Lazarević-Pašti, Tamara D; Bondžić, Aleksandra M; Vasić, Vesna M

    2013-01-01

    Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation, induced by various inhibitors, leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the enzyme as their primary target, are appl...

  16. Isolation and analysis of polysaccharide showing high hyaluronidase inhibitory activity in Nostochopsis lobatus MAC0804NAN.

    Yamaguchi, Yuji; Koketsu, Mamoru

    2016-03-01

    An active substance with high hyaluronidase inhibitory effect was isolated from the edible cyanobacterium Nostochopsis lobatus MAC0804NAN strain and characterized. The active component in the hot water extract was purified by anion exchange and gel filtration chromatography and was found to be a polysaccharide. The IC(50) against hyaluronidase of the purified polysaccharide was 7.18 μg/ml whose inhibitory activity is 14.5 times stronger than that of disodium cromoglycate (DSCG), an anti-allergy medication. The carbohydrate composition which was analyzed by GC-MS and NMR was found to be composed mainly of glucose, glucuronic acid, fucose, 2-O-methylfucose, mannose, galactose and xylose. PMID:26296532

  17. Indomethacin Analogues that Enhance Doxorubicin Cytotoxicity in Multidrug Resistant Cells without Cox Inhibitory Activity.

    Arisawa, Mitsuhiro; Kasaya, Yayoi; Obata, Tohru; Sasaki, Takuma; Ito, Mika; Abe, Hiroshi; Ito, Yoshihiro; Yamano, Akihito; Shuto, Satoshi

    2011-05-12

    Conformationally restricted indomethacin analogues were designed and prepared from the corresponding 2-substituted indoles, which were synthesized by a one-pot isomerization/enamide-ene metathesis as the key reaction. Conformational analysis by calculations, NMR studies, and X-ray crystallography suggested that these analogues were conformationally restricted in the s-cis or the s-trans form due to the 2-substituent as expected. Their biological activities on cyclooxygenase-1 (COX-1) inhibition, cyclooxygenase-2 (COX-2) inhibition, and modulation of MRP-1-mediated multidrug resistance (MDR) are described. Some of these indomethacin analogues enhanced doxorubicin cytotoxicity, although they do not have any COX inhibitory activity, which suggests that the MDR-modulating effect of an NSAID can be unassociated with its COX-inhibitory activity. This may be an entry into the combination chemotherapy of doxorubicin with a MDR modulator. PMID:24900317

  18. Anti-obesity effect of Dioscorea nipponica Makino with lipase-inhibitory activity in rodents.

    Kwon, Chong-Suk; Sohn, Ho Yong; Kim, Sung Hee; Kim, Ji Hyun; Son, Kun Ho; Lee, Jeong Soon; Lim, Jin Kyu; Kim, Jong-Sang

    2003-07-01

    In the process of screening for pancreatic lipase inhibitors, which could be used as an anti-obesity measure, the methanol extract of Dioscorea nipponica Makino powder (DP) appeared to have potent inhibitory activity against porcine pancreatic lipase with an IC50 value of 5-10 microg/ml, where the enzyme activity was assayed by using 4-methylumbelliferyl oleate as a substrate. Further purification of active components present in the herb generated dioscin that belongs to the saponin family. Dioscin and its aglycone, diosgenin, both suppressed the time-dependent increase of blood triacylglycerol level when orally injected with corn oil to mice, suggesting their inhibitory potential against fat absorption. Sprague-Dawley rats fed on a high-fat diet containing 5% Dioscorea nipponica Makino and 40% beef tallow gained significantly less body weight and adipose tissue than control animals fed on a high-fat diet alone during an 8-week experimental period (P<0.05). PMID:12913286

  19. α-GLUCOSIDASE AND α -AMYLASE INHIBITORY ACTIVITIES OF RAPHANUS SATIVUS LINN.

    R. Vadivelan et al

    2012-09-01

    Full Text Available Herbal medicine has been used for many years by different cultures around the world for the treatment of diabetes. There has been an enormous interest in the development of alternative medicines for type 2 diabetes, specifically screening for phytochemicals with the ability to delay or prevent glucose absorption. The goal of the present study is to evaluate the invitro antidiabetic activity of Raphanus sativus ethanolic extract and fractions by α-glucosidase and α -amylase inhibitory activity. Raphanus sativus ethanolic extract and fractions showed dose dependent inhibition of α-glucosidase and α -amylase enzyme and exhibited lower inhibitory activity than acarbose. The study revealed the antidiabetic potential and could be helpful to develop medicinal preparations and nutraceuticals and function foods for diabetes.

  20. Efeito do extrato da casca de Syzygium cumini sobre a atividade da acetilcolinesterase em ratos normais e diabéticos Syzygium cumini bark extract effect on acetylcholinesterase activity in normal and diabetic rats

    Cinthia Melazzo Mazzanti

    2004-06-01

    Full Text Available Este estudo verificou a eficiência do extrato etanólico da casca de Syzygium cumini sobre o sistema colinérgico de ratos normais e diabéticos induzidos com aloxano. Os animais foram divididos em grupo controle (C, tratado com Syzygium cumini (TS, diabético (D e diabético tratado com Syzygium cumini (DS. A atividade da acetilcolinesterase (AChE foi analisada nas seguintes estruturas cerebrais: cerebelo, córtex, estriado e hipocampo. O extrato etanólico da casca de Syzygium cumini na dose de 1g.kg-1 foi administrado diariamente por um período de trinta dias. Foi verificado após este período que o extrato inibiu a atividade da AChE no cerebelo e córtex cerebral dos ratos do grupo DS (PThe present study verified the efficiency of the bark ethanol extract of Syzygium cumini on the cholinergic system of normal and alloxan induced diabetic rats. Thirty-nine female rats were divided in control (C, treated with Syzygium cumini (TS, diabetic (D and diabetic treated with Syzygium cumini (DS. The activity of acetylcholinesterase (AChE was analyzed in the following cerebral structures: cerebellum, cortex, striatum and hippocampus. The extract of the bark of Syzygium cumini in the dose of 1g.kg-1 was administered orally daily for a period of thirty days. After this period the extract inhibited the activity of the AChE in the cerebellum and cerebral cortex of the rats in the DS group (P<0.05 as, compared to TS. In the striatum there was a significant increase in the activity of the AChE in rats of the TS group (P<0.01 when compared to the C group, and in the hippocampus there was no significant variation. These results indicate that the bark extract of "Jambolão"has an inhibitory effect on AChE in the cerebellum and cerebral cortex and an stimulatory effect on striatum, indicating a possible alteration in the functionality of the cholinergic system in such cerebral structures.

  1. In Vitro Antioxidant and Enzymes Inhibitory activity of Chloroform Fraction of Hydroalcoholic extract obtained from Argemone mexicana

    Nayak P

    2013-03-01

    Full Text Available In the present investigation antioxidant and alphaamylase inhibitory activity of chloroform fraction of Argemone mexicana were evaluated. The antioxidant activity of chloroform fraction of A. mexicana was evaluated by DPPH, Super oxide radical Scavenging activity, ABTS radical cation scavenging activity and Nitric oxide radical scavenging activity. Alpha-amylase inhibitory activity of chloroform fraction was evaluated by DNS method respectively. The observed resultant antioxidant activity of chloroform fraction in all studied models was moderate as compared with reference standard Ascorbic acid. The chloroform fraction exhibited appreciable α-amylase inhibitory activity with an IC50 value 48.92μg/ml respectively, when compared with acarbose (IC50 value 83.33μg/ml.In conclusion, from the results of present study it is confirmed that antioxidant and alpha-amylase inhibitory activity of chloroform fraction of A. mexicana may contribute in its earlier observed antidiabetic potential.

  2. Anti-Oxidative and Cholinesterase Inhibitory Effects of Leaf Extracts and Their Isolated Compounds from Two Closely Related Croton Species

    Johannes van Staden; Bhekumthetho Ncube; Mutalib A. Aderogba; Ndhlala, Ashwell R.

    2013-01-01

    A comparative evaluation of the antioxidant and acetylcholinesterase inhibitory activity of the leaf extracts of Croton gratissimus and Croton zambesicus (subgratissimus) and compounds isolated from the extracts was carried out to determine their potential and suitability or otherwise as a substitute for each other in the management of oxidative and neurodegenerative conditions. Different antioxidant assays (DPPH, FRAP, β-carotene-linoleic and the lipid peroxidation models) and the microplate...

  3. Evaluation of 5α-reductase inhibitory activity of certain herbs useful as antiandrogens.

    Nahata, A; Dixit, V K

    2014-08-01

    This study demonstrates 5α-reductase inhibitory activity of certain herbs useful in the management of androgenic disorders. Ganoderma lucidum (Curtis) P. Karst (GL), Urtica dioica Linn. (UD), Caesalpinia bonducella Fleming. (CB), Tribulus terrestris Linn. (TT), Pedalium murex Linn. (PM), Sphaeranthus indicus Linn. (SI), Cuscuta reflexa Roxb. (CR), Citrullus colocynthis Schrad. (CC), Benincasa hispida Cogn. (BH), Phyllanthus niruri Linn. (PN) and Echinops echinatus Linn. (EE) were included in the study. Petroleum ether, ethanol and aqueous extracts of these herbs were tested for their 5α-reductase inhibitory activity against the standard 5α-reductase inhibitor, finasteride. A biochemical method to determine the activity of 5α-reductase was used to evaluate the inhibition of different extracts to the enzyme. The optical density (OD) value of each sample was measured continuously with ultraviolet spectrophotometer for the reason that the substrate NADPH has a specific absorbance at 340 nm. As the enzyme 5α-reductase uses NADPH as a substrate, so in the presence of 5α-reductase inhibitor, the NADPH concentration will increase with the function of time. This method thus implicates the activity of 5α-reductase. The method proved to be extremely useful to screen the herbs for their 5α-reductase inhibitory potential. GL, UD, BH, SI and CR came out to be promising candidates for further exploring their antiandrogenic properties. PMID:23710567

  4. Antioxidant, Iron Chelating and Tyrosinase Inhibitory Activities of Extracts from Talinum triangulare Leach Stem

    Oliveira Amorim, Ana Paula; Campos de Oliveira, Márcia Cristina; de Azevedo Amorim, Thiago; Echevarria, Aurea

    2013-01-01

    The aim of this work is to evaluate the antioxidant activity against the radical species DPPH, the reducing capacity against Fe II ions, and the inhibitory activity on the tyrosinase enzyme of the T. triangulare. Hydromethanolic crude extract provided two fractions after the liquid/liquid partition with chloroform. The Folin-Ciocalteu method determined the total phenolic content of the crude extract (CE) and the hydromethanolic fraction (Fraction 1), resulting in a concentration of 0.5853 g/100 g for Fraction 1, and 0.1400 g/100 g for the CE. Taking into account the results of the DPPH, the free radical scavenging capacity was confirmed. The formation of complexes with Fe II ions was evaluated by UV/visible spectrometry; results showed that CE has complexing power similar to the positive control (Gingko biloba extract).The inhibitory capacity of samples against the tyrosinase enzyme was determined by the oxidation of L-DOPA, providing IC50 values of 13.3 μg·mL−1 (CE) and 6.6 μg·mL−1 (Fraction 1). The values indicate that Fraction 1 was more active and showed a higher inhibitory power on the tyrosinase enzyme than the ascorbic acid, used as positive control. The hydromethanolic extract of T. triangulare proved to have powerful antioxidant activity and to inhibit the tyrosinase enzyme; its potential is increased after the partition with chloroform. PMID:26784338

  5. Antioxidant, Iron Chelating and Tyrosinase Inhibitory Activities of Extracts from Talinum triangulare Leach Stem

    Ana Paula Oliveira Amorim

    2013-07-01

    Full Text Available The aim of this work is to evaluate the antioxidant activity against the radical species DPPH, the reducing capacity against Fe II ions, and the inhibitory activity on the tyrosinase enzyme of the T. triangulare. Hydromethanolic crude extract provided two fractions after the liquid/liquid partition with chloroform. The Folin-Ciocalteu method determined the total phenolic content of the crude extract (CE and the hydromethanolic fraction (Fraction 1, resulting in a concentration of 0.5853 g/100 g for Fraction 1, and 0.1400 g/100 g for the CE. Taking into account the results of the DPPH, the free radical scavenging capacity was confirmed. The formation of complexes with Fe II ions was evaluated by UV/visible spectrometry; results showed that CE has complexing power similar to the positive control (Gingko biloba extract.The inhibitory capacity of samples against the tyrosinase enzyme was determined by the oxidation of L-DOPA, providing IC50 values of 13.3 μg·mL−1 (CE and 6.6 μg·mL−1 (Fraction 1. The values indicate that Fraction 1 was more active and showed a higher inhibitory power on the tyrosinase enzyme than the ascorbic acid, used as positive control. The hydromethanolic extract of T. triangulare proved to have powerful antioxidant activity and to inhibit the tyrosinase enzyme; its potential is increased after the partition with chloroform.

  6. Antioxidant, Iron Chelating and Tyrosinase Inhibitory Activities of Extracts from Talinum triangulare Leach Stem.

    Oliveira Amorim, Ana Paula; Campos de Oliveira, Márcia Cristina; de Azevedo Amorim, Thiago; Echevarria, Aurea

    2013-01-01

    The aim of this work is to evaluate the antioxidant activity against the radical species DPPH, the reducing capacity against Fe II ions, and the inhibitory activity on the tyrosinase enzyme of the T. triangulare. Hydromethanolic crude extract provided two fractions after the liquid/liquid partition with chloroform. The Folin-Ciocalteu method determined the total phenolic content of the crude extract (CE) and the hydromethanolic fraction (Fraction 1), resulting in a concentration of 0.5853 g/100 g for Fraction 1, and 0.1400 g/100 g for the CE. Taking into account the results of the DPPH, the free radical scavenging capacity was confirmed. The formation of complexes with Fe II ions was evaluated by UV/visible spectrometry; results showed that CE has complexing power similar to the positive control (Gingko biloba extract).The inhibitory capacity of samples against the tyrosinase enzyme was determined by the oxidation of L-DOPA, providing IC50 values of 13.3 μg·mL(-1) (CE) and 6.6 μg·mL(-1) (Fraction 1). The values indicate that Fraction 1 was more active and showed a higher inhibitory power on the tyrosinase enzyme than the ascorbic acid, used as positive control. The hydromethanolic extract of T. triangulare proved to have powerful antioxidant activity and to inhibit the tyrosinase enzyme; its potential is increased after the partition with chloroform. PMID:26784338

  7. Acetylcholinesterase: From 3D Structure to Function

    Dvir, Hay; Silman, Israel; Harel, Michal; Rosenberry, Terrone L.; Sussman, Joel L.

    2010-01-01

    By rapid hydrolysis of the neurotransmitter, acetylcholine, acetylcholinesterase terminates neurotransmission at cholinergic synapses. Acetylcholinesterase is a very fast enzyme, functioning at a rate approaching that of a diffusion-controlled reaction. The powerful toxicity of organophosphate poisons is attributed primarily to their potent inhibition of acetylcholinesterase. Acetylcholinesterase inhibitors are utilized in the treatment of various neurological disorders, and are the principal...

  8. Melanogenesis Inhibitory Activity of Two Generic Drugs: Cinnarizine and Trazodone in Mouse B16 Melanoma Cells

    Te-Sheng Chang

    2011-12-01

    Full Text Available More than 200 generic drugs were screened to identify the inhibitory activity on melanogenesis in mouse B16 melanoma cells. Cinnarizine and trazodone were identified as melanogenesis inhibitors. The inhibitory effects of the two drugs on cell survival, melanogenesis, and tyrosinase activity were investigated. The results showed that both cinnarizine and trazodone inhibited melanogenesis in B16 cells by a dose-dependent manner at the non-cytotoxic concentrations. Based on the results of the present study, seeking new melanogenesis inhibitors from generic drugs is an alternative approach to developing new depigmenting agents in cosmeceuticals. Moreover, cinnarizine and trazodone were proven to be good candidates as skin-whitening agents for treatment of skin hyperpigmentation.

  9. Phaeophytins from Thyrsacanthus ramosissimus Moric. with inhibitory activity on human DNA topoisomerase II-{alpha}

    Cabral, Analucia Guedes Silveira; Tenorio-Souza, Fabio Henrique; Moura, Marcelo Dantas; Mota, Sabrina Gondim Ribeiro; Silva Lins, Antonio Claudio da; Dias, Celidarque da Silva; Barbosa-Filho, Jose Maria [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Dept. de Ciencias Frmaceuticas; Giulietti, Ana Maria [Universidade Estadual de Feira de Santana, Feira de Santana, BA (Brazil). Dept. de Ciencias Biologicas; Silva, Tania Maria Sarmento da [Universidade Federal Rural de Pernambuco, Recife, PE (Brazil). Dept. de Ciencias Moleculares; Santos, Creusioni Figueredo dos, E-mail: jbarbosa@ltf.ufpb.br [Universidade Federal da Paraiba (UFPB), Joao Pessoa, PB (Brazil). Dept. de Biologia Molecular

    2012-07-01

    Our study reports the extraction and isolation of a new phaeophytin derivative 15{sup 1}-hydroxy-(15{sup 1}-S)-porphyrinolactone, designated anamariaine (1) herein, isolated from the chloroform fraction of aerial parts of Thyrsacanthus ramosissimus Moric. along with the known 15{sup 1}-ethoxy-(15{sup 1}-S)-porphyrinolactone (2). These compounds were identified by usual spectroscopic methods. Both compounds were subjected to in vitro (inhibitory activity) tests by means of supercoiled DNA relaxation techniques and were shown to display inhibitory activity against human DNA topoisomerase II-{alpha} at 50 {mu}M. Interconversion of these two pigments under the mild conditions of the isolation techniques should be highly unlikely but cannot be entirely ruled out. (author)

  10. Extraction optimization of polyphenols, antioxidant and xanthine oxidase inhibitory activities from Prunus salicina Lindl.

    Yibin LI

    2016-01-01

    Full Text Available Abstract Optimization of polyphenols extraction from plum (Prunus salicina Lindl. was evaluated using response surface methodology. The Box-Behnken experimental results showed the optimal conditions involved an extraction temperature of 59 °C, a sonication time of 47 min, and an ethanol concentration of 61% respectively. The maximum extraction yield of total polyphenols was 44.74 mg gallic acid equivalents per gram of dried plum at optimal conditions. Polyphenol extracts exhibited stronger antioxidant activities than Vc by evaluating of 1,1-diphenyl-2-picrylhydrazyl (DPPH and hydroxyl radical scavenging activity. Furthermore, polyphenol extracts (IC50 = 179 g/mL showed obvious inhibitory effects on xanthine oxidase. These findings suggest that polyphenol extracts from P. salicina can be potentially used as natural antioxidant and xanthine oxidase inhibitory agents.

  11. Bioactive Compounds, Antioxidant, Xanthine Oxidase Inhibitory, Tyrosinase Inhibitory and Anti-Inflammatory Activities of Selected Agro-Industrial By-products

    Ehsan Karimi; Ehsan Oskoueian; Rudi Hendra; Norhani Abdullah

    2011-01-01

    Evaluation of abundantly available agro-industrial by-products for their bioactive compounds and biological activities is beneficial in particular for the food and pharmaceutical industries. In this study, rapeseed meal, cottonseed meal and soybean meal were investigated for the presence of bioactive compounds and antioxidant, anti-inflammatory, xanthine oxidase and tyrosinase inhibitory activities. Methanolic extracts of rapeseed meal showed significantly (P < 0.01) higher phenolics and f...

  12. A fluorescence assay for measuring acetylcholinesterase activity in rat blood and a human neuroblastoma cell line (SH-SY5Y).

    Santillo, Michael F; Liu, Yitong

    2015-01-01

    Acetylcholinesterase (AChE) is an enzyme responsible for metabolism of the neurotransmitter acetylcholine, and inhibition of AChE can have therapeutic applications (e.g., drugs for Alzheimer's disease) or neurotoxic consequences (e.g., pesticides). A common absorbance-based AChE activity assay that uses 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) can have limited sensitivity and be prone to interference. Therefore, an alternative assay was developed, in which AChE activity was determined by measuring fluorescence of resorufin produced from coupled enzyme reactions involving acetylcholine and Amplex Red (10-acetyl-3,7-dihydroxyphenoxazine). The Amplex Red assay was used for two separate applications. First, AChE activity was measured in rat whole blood, which is a biomarker for exposure to AChE inhibitor pesticides. Activity was quantified from a 10(5)-fold dilution of whole blood, and there was a linear correlation between Amplex Red and DTNB assays. For the second application, Amplex Red assay was used to measure AChE inhibition potency in a human neuroblastoma cell line (SH-SY5Y), which is important for assessing pharmacological and toxicological potential of AChE inhibitors including drugs, phytochemicals, and pesticides. Five known reversible inhibitors were evaluated (IC50, 7-225 nM), along with irreversible inhibitors chlorpyrifos-oxon (ki=1.01 nM(-1)h(-1)) and paraoxon (ki=0.16 nM(-1)h(-1)). Lastly, in addition to inhibition, AChE reactivation was measured in SH-SY5Y cells incubated with pralidoxime chloride (2-PAM). The Amplex Red assay is a sensitive, specific, and reliable fluorescence method for measuring AChE activity in both rat whole blood and cultured SH-SY5Y cells. PMID:26165232

  13. Effect of Jatropha curcas Peptide Fractions on the Angiotensin I-Converting Enzyme Inhibitory Activity

    Segura-Campos, Maira R.; Fanny Peralta-González; Arturo Castellanos-Ruelas; Chel-Guerrero, Luis A.; David A. Betancur-Ancona

    2013-01-01

    Hypertension is one of the most common worldwide diseases in humans. Angiotensin I-converting enzyme (ACE) plays an important role in regulating blood pressure and hypertension. An evaluation was done on the effect of Alcalase hydrolysis of defatted Jatropha curcas kernel meal on ACE inhibitory activity in the resulting hydrolysate and its purified fractions. Alcalase exhibited broad specificity and produced a protein hydrolysate with a 21.35% degree of hydrolysis and 34.87% ACE inhibition. U...

  14. Impaired inhibitory control in anorexia nervosa elicited by physical activity stimuli

    Kullmann, Stephanie; Giel, Katrin E.; Hu, Xiaochen; Stephan C Bischoff; Teufel, Martin; Thiel, Ansgar; Zipfel, Stephan; Preissl, Hubert

    2013-01-01

    Besides food restriction, hyperactivity is considered a key behavioral trait of anorexia nervosa (AN), playing a major role in the pathogenesis and progression of the disorder. However, the underlying neurophysiology remains poorly understood. We used functional magnetic resonance imaging during two affective go/no-go tasks to probe inhibitory control in response to stimuli depicting physical activity vs inactivity and food vs non-food in AN patients compared with 26 healthy athlete and non-a...

  15. IN VITRO SOLUBLE EPOXIDE HYDROLASE ENZYME INHIBITORY ACTIVITY OF SOME NOVEL CHALCONE DERIVATIVES

    Kuppusamy Asokkumar; Lokeswari Prathyusha Tangella; Muthusamy Umamaheshwari; Thirumalaisamy Shivashanmugam; Varadharajan Subhadradevi; Puliyath Jagannath; Arumugam Madeswaran

    2012-01-01

    Objective Soluble epoxide hydrolase (sEH) belongs to the α/β -hydrolase superfamily, a subclass of α/β proteins. Chalcones are chemical compounds that show hopeful obliging efficacy in controlling numerous diseases. The main objective of the study is to evaluate the sEH inhibitory activity of some synthesized chalcone derivatives and identification of its mode of inhibition. Methods Four different chalcone derivatives (PC-1 to PC-4) were selected for synthesis by Claisen-Schmidt method. The i...

  16. Mushroom tyrosinase inhibitory activity and major fatty acid constituents of Amazonian native flora oils

    Raquel da Silva Teixeira; Paula Rafaela Rocha; Hudson Caetano Polonini; Marcos Antônio Fernandes Brandão; Maria das Graças Afonso Miranda Chaves; Nádia Rezende Barbosa Raposo

    2012-01-01

    In order to treat hyperpigmentation-related problems, there has been a global trend in developing cosmetics claiming to have skin-whitening properties, which act by inhibiting melanin biosynthesis. The objective of this work was to evaluate the in vitro mushroom tyrosinase inhibitory activity of five Amazonian native flora oils, and so to verify the possibility of their incorporation into cosmetic products. In addition, the fatty acid composition of the essential oils was determined by gas ch...

  17. Virtual Screening Analysis and In-vitro Xanthine Oxidase Inhibitory Activity of Some Commercially Available Flavonoids

    Umamaheswari, Muthuswamy; Madeswaran, Arumugam; Asokkumar, Kuppusamy

    2013-01-01

    Allopurinol, the xanthine oxidase inhibitor, is the only drug available for the treatment of gout. We examined the xanthine oxidase inhibitory activity of some commercially available flavonoids such asepigallocatechin, acacatechin, myricetin, naringenin, daidzein and glycitein by virtual screening and in-vitro studies. The interacting residues within the complex model and their contact types were identified. The virtual screening analysis were carried out using AutoDock 4.2 and in-vitro xanth...

  18. In Silico Docking studies of Aldose Reductase Inhibitory activity of selected Flavonoids

    Muthuswamy Umamaheswari; C. S. Aji; Kuppusamy Asokkumar; Thirumalaisamy Sivashanmugam; Varadharajan Subhadradevi; Puliyath Jagannath; Arumugam Madeswaran

    2012-01-01

    New drugs for the inhibition of the enzyme aldose reductase are in development and they have to be screened before being considered for preclinical and clinical evaluation. The current study deals with the evaluation of the cyclooxygenase inhibitory activity of flavonoids using in silico docking studies. In this perspective, flavonoids like Farobin-A, Gericudranin- B, Glaziovianin-A, Rutin, and Xanthotoxin were selected. Epalrestat, a known aldose reductase inhibitor was used as the standard....

  19. Evaluation of the antiinflammatory and phospholipase-inhibitory activity of calpactin II/lipocortin I.

    Northup, J K; Valentine-Braun, K A; Johnson, L K; Severson, D L; Hollenberg, M D

    1988-01-01

    We have examined the ability of a highly purified 38-kD phospholipase-inhibitory protein (p38) isolated from human placental membranes that is also a preferred substrate for the epidermal growth factor-urogastrone (EGF-URO) receptor/kinase, to block the release of arachidonate from zymosan-stimulated murine peritoneal macrophages in vitro and to exhibit antiinflammatory activity in a carrageenin rat paw edema test in vivo. The ability of glucocorticoids to increase the amounts of this protein...

  20. Nutritional Composition, α-Glucosidase Inhibitory and Antioxidant Activities of Ophiopogon japonicus Tubers

    Yancui Wang; Feng Liu; Zongsuo Liang

    2015-01-01

    Ophiopogon japonicus tubers have been widely used as food and traditional Chinese medicine in China. However, their nutritional composition has not been fully reported yet. This study aimed to analyze the nutritional composition of O. japonicus tubers. The α-glucosidase inhibitory and antioxidant activities of the extracts obtained from O. japonicus tubers were also evaluated by in vitro assays. The results indicated that O. japonicus tubers are rich in carbohydrates, proteins, minerals, and ...

  1. Antioxidant and α-Glucosidase Inhibitory Activities of Isolated Compounds from Ipomoea aquatica

    Umar Lawal; Khozirah Shaari; Intan Safinar Ismail; Alfi Khatib; Faridah Abas

    2016-01-01

    Ipomoea aquatica Forsk is a green leafy vegetable that is a rich source of amino acids and vitamins. Antioxidant and α-glucosidase inhibitory activities of the hexane (IAHE) and methanol (IAME) fractions of the vegetable portion of I. aquatica were investigated. The IAME fraction exhibited a strong scavenging effect of the 2,2-diphenyl-2-picryl hydrazyl (DPPH) free radicals, and this fraction contained the highest phenolic contents. Phytochemical investigation of the IAME fraction yielded thr...

  2. Bioactive Compounds, Antioxidant, Xanthine Oxidase Inhibitory, Tyrosinase Inhibitory and Anti-Inflammatory Activities of Selected Agro-Industrial By-products

    Ehsan Karimi

    2011-11-01

    Full Text Available Evaluation of abundantly available agro-industrial by-products for their bioactive compounds and biological activities is beneficial in particular for the food and pharmaceutical industries. In this study, rapeseed meal, cottonseed meal and soybean meal were investigated for the presence of bioactive compounds and antioxidant, anti-inflammatory, xanthine oxidase and tyrosinase inhibitory activities. Methanolic extracts of rapeseed meal showed significantly (P < 0.01 higher phenolics and flavonoids contents; and significantly (P < 0.01 higher DPPH and nitric oxide free radical scavenging activities when compared to that of cottonseed meal and soybean meal extracts. Ferric thiocyanate and thiobarbituric acid tests results showed rapeseed meal with the highest antioxidant activity (P < 0.01 followed by BHT, cotton seed meal and soybean meal. Rapeseed meal extract in xanthine oxidase and tyrosinase inhibitory assays showed the lowest  IC50 values  followed by cottonseed and soybean meals. Anti-inflammatory assay using IFN-γ/LPS stimulated RAW 264.7 cells indicated rapeseed meal is a potent source of anti-inflammatory agent. Correlation analysis showed that phenolics and flavonoids were highly correlated to both antioxidant and anti-inflammatory activities. Rapeseed meal was found to be promising as a natural source of bioactive compounds with high antioxidant, anti-inflammatory, xanthine oxidase and tyrosinase inhibitory activities in contrast to cotton and soybean meals.

  3. A human acetylcholinesterase gene identified by homology to the Ace region of Drosophila.

    Soreq, H.; Zevin-Sonkin, D; Avni, A.; Hall, L. M.; Spierer, P

    1985-01-01

    The Ace locus of the Drosophila genome controls biosynthesis of the neurotransmitter-hydrolyzing enzyme acetylcholinesterase (acetylcholine acetylhydrolase, EC 3.1.1.7). We injected the mRNA species hybridizing with DNA fragments from this region into Xenopus oocytes, in which acetylcholinesterase mRNA is translated into active acetylcholinesterase. A 2.0-kilobase (kb) fragment of DNA from this region selectively hybridizes with Drosophila mRNA capable of inducing the biosynthesis of acetylch...

  4. Immobilization of Acetylcholinesterase on Screen-Printed Electrodes. Application to the Determination of Arsenic(III)

    M. Julia Arcos-Martínez; Olga Domínguez-Renedo; Silvia Sanllorente-Méndez

    2010-01-01

    Enzymatic amperometric procedures for measuring arsenic, based on the inhibitive action of this metal on acetylcholinesterase enzyme activity, have been developed. Screen-printed carbon electrodes (SPCEs) were used with acetylcholinesterase covalently bonded directly to its surface. The amperometric response of acetylcholinesterase was affected by the presence of arsenic ions, which caused a decrease in the current intensity. The experimental optimum working conditions of pH, substrate concen...

  5. Toxoplasma gondii infection regulates the balance of activating and inhibitory receptors on decidual natural killer cells.

    Xiaoyan Xu

    Full Text Available Inhibitory receptors and activating receptor expressed on decidual natural killer (dNK cells are generally believed to be important in abnormal pregnancy outcomes and induced adverse pregnancy. However, if Toxoplasma gondii (T. gondii infection induced abnormal pregnancy was related to dNK cells changes is not clear. In this study, we used human dNK cells co-cultured with human extravillous cytotrophoblast (EVT cells following YFP-Toxoplasma gondii (YFP-T. gondii infection in vitro and established animal pregnant infection model. Levels of inhibitory receptors KIR2DL4 and ILT-2, their ligand HLA-G, and activating receptor NKG2D in human decidua, and NKG2A and its ligand Qa-1 and NKG2D in mice uterine were analyzed by real-time PCR and flow cytometry with levels of NKG2D significantly higher than those of KIR2DL4 and ILT-2 in vitro and in invo. The level of NKG2D was positively correlated with cytotoxic activity of dNK cells in vitro. Numbers of abnormal pregnancies were significantly greater in the infected group than in the control group. This result demonstrated that the increased NKG2D expression and imbalance between inhibitory receptors of dNK cells and HLA-G may contribute to abnormal pregnancy outcomes observed upon maternal infection with T. gondii.

  6. Inhibitory effects of ofloxacin and cefepime on enzyme activity of 6-phosphogluconate dehydrogenase from chicken liver.

    Erat, Mustafa; Sakiroğlu, Halis

    2007-01-01

    In this study, effects of some antibiotics, namely, ofloxacin, cefepime, cefazolin, and ampicillin on the in vitro enzyme activity of 6-phosphogluconate dehydrogenase have been investigated. For this purpose, 6-phosphogluconate dehydrogenase was purified from chicken liver 535-fold with a yield of 18% by using ammonium sulphate precipitation, 2',5'-ADP Sepharose 4B affinity chromatography, and Sephadex G-200 gel filtration chromatography. In order to check the purity of the enzyme, SDS polyacylamide gel electrophoresis (SDS-PAGE) was performed. This analysis revealed a highly pure enzyme band on the gel. Among the antibiotics, ofloxacin and cefepime exhibited inhibitory effects, but cefazolin and ampicillin showed neither important inhibitory nor activatory effects on the enzyme activity. The measured I(50) values by plotting activity percent vs. inhibitor concentration, [I(50)] were 0.1713 mM for ofloxacin and 6.0028 mM for cefepime. Inhibition constants, K(i), for ofloxacin and cefepime were also calculated as 0.2740 +/- 0.1080 mM and 12.869 +/- 16.6540 mM by means of Lineweaver-Burk graphs, and inhibition types of the antibiotics were found out to be non-competitive and competitive, respectively. It has been understood from the calculated inhibitory parameters that the purified chicken enzyme has been quite inhibited by these two antimicrobials. PMID:17305608

  7. Phospholipase A2 activation enhances inhibitory synaptic transmission in rat substantia gelatinosa neurons.

    Liu, Tao; Fujita, Tsugumi; Nakatsuka, Terumasa; Kumamoto, Eiichi

    2008-03-01

    Phospholipase A(2) (PLA(2)) activation enhances glutamatergic excitatory synaptic transmission in substantia gelatinosa (SG) neurons, which play a pivotal role in regulating nociceptive transmission in the spinal cord. By using melittin as a tool to activate PLA(2), we examined the effect of PLA(2) activation on spontaneous inhibitory postsynaptic currents (sIPSCs) recorded at 0 mV in SG neurons of adult rat spinal cord slices by use of the whole cell patch-clamp technique. Melittin enhanced the frequency and amplitude of GABAergic and glycinergic sIPSCs. The enhancement of GABAergic but not glycinergic transmission was largely depressed by Na(+) channel blocker tetrodotoxin or glutamate-receptor antagonists (6-cyano-7-nitroquinoxaline-2,3-dione and/or dl-2-amino-5-phosphonovaleric acid) and also in a Ca(2+)-free Krebs solution. The effects of melittin on glycinergic sIPSC frequency and amplitude were dose-dependent with an effective concentration of approximately 0.7 microM for half-maximal effect and were depressed by PLA(2) inhibitor 4-bromophenacyl bromide or aristolochic acid. The melittin-induced enhancement of glycinergic transmission was depressed by lipoxygenase inhibitor nordihydroguaiaretic acid but not cyclooxygenase inhibitor indomethacin. These results indicate that the activation of PLA(2) in the SG enhances GABAergic and glycinergic inhibitory transmission in SG neurons. The former action is mediated by glutamate-receptor activation and neuronal activity increase, possibly the facilitatory effect of PLA(2) activation on excitatory transmission, whereas the latter action is due to PLA(2) and subsequent lipoxygenase activation and is independent of extracellular Ca(2+). It is suggested that PLA(2) activation in the SG could enhance not only excitatory but also inhibitory transmission, resulting in the modulation of nociception. PMID:18216222

  8. Altered Levels of Acetylcholinesterase in Alzheimer Plasma

    García Ayllón, María Salud; Riba Llena, Iolanda; Serra Basante, Carol; Alom, Jordi; Boopathy, Rathnam; Sáez-Valero, Javier

    2010-01-01

    Background Many studies have been conducted in an extensive effort to identify alterations in blood cholinesterase levels as a consequence of disease, including the analysis of acetylcholinesterase (AChE) in plasma. Conventional assays using selective cholinesterase inhibitors have not been particularly successful as excess amounts of butyrylcholinesterase (BuChE) pose a major problem. Principal Findings Here we have estimated the levels of AChE activity in human plasma by first imm...

  9. Effect of an antioxidant combination on the distribution of acetylcholinesterase and adenosine triphosphatase activities in the cerebellum of in lindane-intoxicated mice

    Devendra Kumar Bhatt

    2013-04-01

    Full Text Available Objective: The present investigation ascertains a protective potential of a combination of antioxidants against lindane-induced toxicity in cerebellum of mice. Methods: For the study, animals are divided into four groups. First group is control and it is given only vehicle. Second group is treated with lindane and analysed if there are any lesions in the brain. Third group is purely antioxidants treated group; four antioxidants, i.e. resveratrol, ascorbic acid, alpha lipoic acid and vitamin E, are subcutaneously administered in a suitable combination to the animals of this group. Fourth group is treated with both lindane and antioxidants. Acetylcholinesterase (AChE and adenosine triphosphatase (ATPase activities are used as histochemical markers for manifestation of lindane-induced acute toxicity. Biochemical levels of glutathione (GSH and thiobarbituric acid reactive substances (TBARS were also evaluated for different groups to confirm the toxicity of lindane in cerebellum. Results: Treatment with lindane caused decrease in AChE and ATPase activities, and GSH levels in cerebellum whereas a significant increase was recorded in TBARS. Antioxidants treatment increased the enzymatic activities. A significant rise in GSH level was recorded in the antioxidant treatment group as compared to group I and group II whereas TBARS levels were significantly reduced. GSH and TBARS levels altered significantly in group IV as compared to control group and lindane-treated group. In group III, AChE and ATPase activities increased in layers and nuclei of cerebellum as compared to control group. Conclusions: Since the use of antioxidants prevents the inhibition of AChE and ATPase, functions which are altered due to lindane-toxicity may be protected. [J Exp Integr Med 2013; 3(2.000: 103-112

  10. The herbicide glyphosate is a weak inhibitor of acetylcholinesterase in rats.

    Larsen, Karen E; Lifschitz, Adrián L; Lanusse, Carlos E; Virkel, Guillermo L

    2016-07-01

    The current work evaluated the inhibitory potency of the herbicide glyphosate (GLP) on acetylcholinesterase (AChE) activity in male and female rat tissues. The AChE activity in brain was higher (p<0.05) than those observed in kidney (females: 2.2-fold; males: 1.9-fold), liver (females: 6-fold; males: 6.9-fold) and plasma (females: 14.7-fold; males: 25.3-fold). Enzyme activities were higher in presence of 10mM GLP compared to those measured at an equimolar concentration of the potent AChE inhibitor dichlorvos (DDVP). Moreover, IC50s for GLP resulted between 6×10(4)- and 6.8×10(5)-fold higher than those observed for DDVP. In conclusion, GLP is a weak inhibitor of AChE in rats. PMID:27258137

  11. The availability of attentional resources modulates the inhibitory strength related to weakly activated priming.

    Wang, Yongchun; Wang, Yonghui; Liu, Peng; Dai, Dongyang; Di, Meilin; Chen, Qiang

    2016-08-01

    The current study investigated the role of attention in inhibitory processes (the inhibitory processes described in the current study refer only to those associated with masked or flanked priming) using a mixed paradigm involving the negative compatibility effect (NCE) and object-based attention. Accumulating evidence suggests that attention can be spread more easily within the same object, which increases the availability of attentional resources, than across different objects. Accordingly, we manipulated distractor location (with primes presented in the same object versus presented in different objects) together with prime/target compatibility (compatible versus incompatible) and prime-distractor stimulus onset asynchrony (SOA, 23 ms vs 70 ms). The aim was to investigate whether inhibitory processes related to weakly activated priming, which have been previously assumed to be automatic, depend on the availability of attentional resources. The results of Experiment 1 showed a significant NCE for the 70-ms SOA when the prime and distractor were presented in the same object (greater attentional resource availability); however, reversed NCEs were obtained for all other conditions. Experiment 2 was designed to disentangle whether the results of Experiment 1 were affected by the prime position, and the results indicated that the prime position did not modulate the NCE in Experiment 1. Together, these results are consistent with the claim that the availability of attentional resources modulates the inhibitory strength related to weakly activated priming. Specifically, if attentional resources are assigned to the distractor when it is presented in the same object as the prime, the strength of the inhibition elicited by the distractor may increase and reverse the activation elicited by the prime, which could lead to a significant NCE. PMID:27198916

  12. Inhibitory activity of garlic (Allium sativum extract on multidrug-resistant Streptococcus mutans

    Fani M

    2007-01-01

    Full Text Available Garlic ( Allium sativum extract has been known to have inhibitory activity on various pathogenic bacteria, viruses and fungi. The objective of present investigation was to study in vitro inhibitory activity of garlic extract on multidrug-resistant (MDR strains of Streptococcus mutans isolated from human carious teeth. Filter sterilized aqueous extract of garlic was prepared and used in the present study. For isolation of S. mutans , extracted human carious teeth were cultured in Todd-Hewit broth and Mitis-Salivarius-Bacitracin agar. S. mutans was characterized by colony morphology, biochemical tests and other conventional bacteriological procedures. Disk sensitivity tests and broth dilution methods were used to determine antibiotic sensitivity profile and inhibitory activity of garlic extract on S. mutans isolated from carious teeth. Of 105 carious teeth tested, 92 (87.6% isolates of S. mutans were recovered, among which 28 (30.4% were MDR since they were resistant to four or more antibiotics. The highest rate of resistance was observed for tetracycline (30.4% and least resistance (0% to teichoplanin and vancomycin while 22.8% and 23.9% of the isolates were resistant to penicillin and amoxicillin, respectively. Chlorhexidine minimum inhibitory concentration (MIC for MDR and non-MDR S. mutans varied from 2 to 16 µg ml−1 and from 0.25 to 1 µg ml−1 , respectively ( P < 0.05. All isolates, MDR and non-MDR of S. mutans were sensitive to garlic extract with the MIC ranging from 4 to 32 mg ml−1 . Considering in vitro data obtained in the present study, mouthwashes or toothpaste containing optimum concentration of garlic extract could be used for prevention of dental caries.

  13. [Inhibitory activity of vaginal Lactobacillus bacteria on yeasts causing vulvovaginal candidiasis].

    Strus, Magdalena; Brzychczy-Włoch, Monika; Kucharska, Agnieszka; Gosiewski, Tomasz; Heczko, Piotr B

    2005-01-01

    Growing frequency of therapeutical failures of vulvovaginal candidiasis, resulting from resistance of certain species of Candida to imidazole agents, raises interest in the use of probiotics from Lactobacillus genera as prophylaxis. Unfortunately, little is known about inhibitory mechanisms of Lactobacillus on Candida. The aim of this study was to compare the activity of selected Lactobacillus species, representing the physiological vaginal flora, against Candida as well as investigation whether their inhibitory activity against Candida is related strictly to hydrogen peroxide and lactic acid production. 125 strains from vaginal smears of healthy women were classified by making use of phenotypic and genotypic methods. The majority of strains belonged to L. acidophilus: L. acidophilus sensu stricto, L. crispatus, L. gasseri and L. johnsonii as well as L. fermentum and L. plantarum species. Culture supernatants of selected 25 strains representing the isolated species were examined for their inhibitory activity against the growth of Candida albicans and C. glabrata. The results showed that the strongest and the fastest activity against C. albicans was demonstrated by L. delbrueckii strains, producing the largest quantities of hydrogen peroxide. On the other hand, extended activity, demonstrable after 24 hours, was shown by non-H2O2 producing L. plantarum supernatants. Growth of C. glabrata was not inhibited by any of the examined strains of Lactobacillus. Comparison of activity of live active cultures of Lactobacillus strains and their mixtures with this of pure H2O2 and lactic acid has shown that pure chemical compounds were less active than the cultures. This suggests that mixtures of Lactobacillus strains are in cooperation with each other using many different metabolites. PMID:16130291

  14. Inhibitory noise

    Alain Destexhe

    2010-03-01

    Full Text Available Cortical neurons in vivo may operate in high-conductance states, in which the major part of the neuron's input conductance is due to synaptic activity, sometimes several-fold larger than the resting conductance. We examine here the contribution of inhibition in such high-conductance states. At the level of the absolute conductance values, several studies have shown that cortical neurons in vivo are characterized by strong inhibitory conductances. However, conductances are balanced and spiking activity is mostly determined by fluctuations, but not much is known about excitatory and inhibitory contributions to these fluctuations. Models and dynamic-clamp experiments show that, during high-conductance states, spikes are mainly determined by fluctuations of inhibition, or by inhibitory noise. This stands in contrast to low-conductance states, in which excitatory conductances determine spiking activity. To determine these contributions from experimental data, maximum likelihood methods can be designed and applied to intracellular recordings in vivo. Such methods indicate that action potentials are indeed mostly correlated with inhibitory fluctuations in awake animals. These results argue for a determinant role for inhibitory fluctuations in evoking spikes, and do not support feed-forward modes of processing, for which opposite patterns are predicted.

  15. Synthesis of Some New Thiazole Derivatives and Their Biological Activity Evaluation

    Leyla Yurttaş

    2015-01-01

    Full Text Available New 2-(4-arylpiperazine-1-yl-N-[4-(2-(4-substituted phenylthiazol-4-ylphenyl]acetamide derivatives were synthesized and evaluated for their antimicrobial and anticholinesterase activities. Acetylcholinesterase inhibitory activities of the compounds were found weak contrary to expectations. It is unlikely that antifungal activity of the compounds was found significant, especially against Candida parapsilosis.

  16. In vitro α-glucosidase inhibitory activity of phenolic constituents from aerial parts of Polygonum hyrcanicum

    Moradi-Afrapoli Fahimeh

    2012-09-01

    Full Text Available Abstract Background and the purpose of the study The early stage of diabetes mellitus type 2 is associated with postprandial hyperglycemia. Hyperglycemia is believed to increase the production of free radicals and reactive oxygen species, leading to oxidative tissue damage. In an effort of identifying herbal drugs which may become useful in the prevention or mitigation of diabetes, biochemical activities of Polygonum hyrcanicum and its constituents were studied. Methods Hexane, ethylacetate and methanol extracts of P. hyrcanicum were tested for α-glucosidase inhibitory, antioxidant and radical scavenging properties. Active constituents were isolated and identified from the methanolic extract in an activity guided approach. Results A methanolic extract from flowering aerial parts of the plant showed notable α-glucosidase inhibitory activity (IC50 = 15 μg/ml. Thirteen phenolic compounds involving a cinnamoylphenethyl amide, two flavans, and ten flavonols and flavonol 3-O-glycosides were subsequently isolated from the extract. All constituents showed inhibitory activities while compounds 3, 8 and 11 (IC50 = 0.3, 1.0, and 0.6 μM, respectively were the most potent ones. The methanol extract also showed antioxidant activities in DPPH (IC50 = 76 μg/ml and FRAP assays (1.4 mmol ferrous ion equivalent/g extract. A total phenol content of 130 mg/g of the extract was determined by Folin-Ciocalteu reagent. Conclusion This study shows that P. hyrcanicum contains phenolic compounds with in vitro activity that can be useful in the context of preventing or mitigating cellular damages linked to diabetic conditions.

  17. In Vitro Alpha-Glucosidase Inhibitory Activity of Phenolic Constituents from Aerial Parts of Polygonum Hyrcanicum

    F Moradi-Afrapoli

    2012-09-01

    Full Text Available Background and the purpose of the study The early stage of diabetes mellitus type 2 is associated with postprandial hyperglycemia. Hyperglycemia is believed to increase the production of free radicals and reactive oxygen species, leading to oxidative tissue damage. In an effort of identifying herbal drugs which may become useful in the prevention or mitigation of diabetes, biochemical activities of Polygonum hyrcanicum and its constituents were studied. Methods:Hexane, ethylacetate and methanol extracts of P. hyrcanicum were tested for alpha-glucosidase inhibitory, antioxidant and radical scavenging properties. Active constituents were isolated and identified from the methanolic extract in an activity guided approach.Results:A methanolic extract from flowering aerial parts of the plant showed notable alpha-glucosidase inhibitory activity (IC50 = 15 mug/ml. Thirteen phenolic compounds involving a cinnamoylphenethyl amide, two flavans, and ten flavonols and flavonol 3-O-glycosides were subsequently isolated from the extract. All constituents showed inhibitory activities while compounds 3, 8 and 11 (IC50 = 0.3, 1.0, and 0.6 muM, respectively were the most potent ones. The methanol extract also showed antioxidant activities in DPPH (IC50 = 76 mug/ml and FRAP assays (1.4 mmol ferrous ion equivalent/g extract. A total phenol content of 130 mg/g of the extract was determined by Folin-Ciocalteu reagent. Conclusion:This study shows that P. hyrcanicum contains phenolic compounds with in vitro activity that can be useful in the context of preventing or mitigating cellular damages linked to diabetic conditions.

  18. 5-Lipoxygenase and cyclooxygenase-1 inhibitory active compounds from Atractylodes lancea.

    Resch, M; Steigel, A; Chen, Z L; Bauer, R

    1998-03-01

    Lipophilic extracts of Atractylodes lancea rhizomes exhibited potent inhibitory activities in 5-lipoxygenase [IC50 (5-LOX) = 2.9 micrograms/mL (n-hexane extract)] and cyclooxygenase-1 [IC50 (COX-1) = 30.5 micrograms/mL (n-hexane extract)] enzymatic assays. Bioactivity-guided fractionation of the n-hexane extract led to the isolation of a new compound atractylochromene (1), a potent inhibitor in both test systems [IC50 (5-LOX) = 0.6 microM, IC50 (COX-1) = 3.3 microM]. Also obtained was 2-[(2E)-3,7-dimethyl-2,6-octadienyl]-6-methyl-2,5-cyclohexadiene-1 ,4-dione (2), which showed a selective inhibitory activity against 5-LOX [IC50 (5-LOX) 0.2 microM, IC50 (COX-1) 64.3 microM]. The sesquiterpene atractylon (3) and the coumarin osthol (4) turned out to be moderate but selective 5-lipoxygenase inhibitors. Atractylenolides I (5), II (6), and III (7) showed no significant inhibitory effects for either enzyme. Structures were established by spectral data interpretation. PMID:9544564

  19. Evaluation of Selected Culinary-Medicinal Mushrooms for Antioxidant and ACE Inhibitory Activities

    Noorlidah Abdullah

    2012-01-01

    Full Text Available Considering the importance of diet in prevention of oxidative stress-related diseases including hypertension, this study was undertaken to evaluate the in vitro antioxidant and ACE inhibitory activities of selected culinary-medicinal mushrooms extracted by boiling in water for 30 min. Antioxidant capacity was measured using the following assays: DPPH free radical scavenging activity, β-carotene bleaching, inhibition of lipid peroxidation, reducing power ability, and cupric ion reducing antioxidant capacity (CUPRAC. Antioxidant potential of each mushroom species was calculated based on the average percentages relative to quercetin and summarized as Antioxidant Index (AI. Ganoderma lucidum (30.1%, Schizophyllum commune (27.6%, and Hericium erinaceus (17.7% showed relatively high AI. Total phenolics in these mushrooms varied between 6.19 to 63.51 mg GAE/g extract. In the ACE inhibitory assay, G. lucidum was shown to be the most potent species (IC50 = 50 μg/mL. Based on our findings, culinary-medicinal mushrooms can be considered as potential source of dietary antioxidant and ACE inhibitory agents.

  20. Chemical constituents of Swertia longifolia Boiss. with α-amylase inhibitory activity

    Soodabeh Saeidnia

    2016-01-01

    Full Text Available α-Amylase inhibitors play a critical role in the control of diabetes and many of medicinal plants have been found to act as α-amylase inhibitors. Swertia genus, belonging to the family Gentianaceae, comprises different species most of which have been used in traditional medicine of several cultures as antidiabetic, anti-pyretic, analgesic, liver and gastrointestinal tonic. Swertia longifolia Boiss. is the only species of Swertia growing in Iran. In the present investigation, phytochemical study of S. longifolia was performed and α-amylase inhibitory effects of the plant fractions and purified compounds were determined. Aerial parts of the plant were extracted with hexane, chloroform, methanol and water, respectively. The components of the hexane and chloroform fractions were isolated by different chromatographic methods and their structures were determined by 1 H NMR and 13 C NMR data. α-Amylase inhibitory activity was determined by a colorimetric assay using 3,5-dinitro salysilic acid. During phytochemical examination, α-amyrin, β-amyrin and β-sitosterol were purified from the hexane fraction,while ursolic acid, daucosterol and swertiamarin were isolated from chloroform fraction. The results of the biochemical assay revealed α-amylase inhibitory activity of hexane, chloroform, methanol and water fractions, of which the chloroform and methanol fractions were more potent (IC 50 16.8 and 18.1 mg/ml, respectively. Among examined compounds, daucosterol was found to be the most potent α-amylase inhibitor (57.5% in concentration 10 mg/ml. With regard to α-amylase inhibitory effects of the plant extracts, purified constituents, and antidiabetic application of the species of Swertia genus in traditional medicine of different countries, S. longifolia seems more appropriate species for further mechanistic antidiabetic evaluations.

  1. Xanthine oxidase inhibitory activity of the methanolic extracts of selected Jordanian medicinal plants

    Mohammad M Hudaib

    2011-01-01

    Full Text Available Background: The search for novel xanthine oxidase (XO inhibitors with a higher therapeutic activity and fewer side effects are desired not only to treat gout but also to combat various other diseases associated with the XO activity. At present, the potential of developing successful natural products for the management of XO-related diseases is still largely unexplored. In the present study, we have screened the methanolic extracts of various Jordanian medicinal plants for their XO inhibitory activities using an optimized protocol. Materials and Methods: The methanolic extracts of 23 medicinal plants, belonging to 12 families, were tested in vitro, at 200 μg/ml concentrations, for their XO inhibitory potential. The dose-dependent inhibition profiles of the most active plants were further evaluated by estimating the IC 50 values of their corresponding extracts. Results: Six plants were found most active (% inhibition more than 39%. These plants are Salvia spinosa L. (IC 50 = 53.7 μg/ml, Anthemis palestina Boiss. (168.0 μg/ml, Chrysanthemum coronarium L. (199.5 μg/ml, Achillea biebersteinii Afansiev (360.0 μg/ml, Rosmarinus officinalis L. (650.0 μg/ml, and Ginkgo biloba L. (595.8 μg/ml. Moreover, four more plants, namely Lavandula angustifolia Mill. (28.7% inhibition, Helianthemum ledifolium (L. Mill. (28.4%, Majorana syriaca (L. Kostel. (25.1%, and Mentha spicata L. (22.5% showed a XO inhibitory activity in the range of 22-30%. Conclusion: The study showed that many of the tested plant species are potential sources of natural XO inhibitors that can be developed, upon further investigation, into successful herbal drugs for treatment of gout and other XO-related disorders.

  2. Changes in Behavior and Brain Acetylcholinesterase Activity in Mosquito Fish, Gambusia affinis in Response to the Sub-Lethal Exposure to Chlorpyrifos

    R. Nageswara Rao

    2005-12-01

    Full Text Available Sub-lethal studies of chlorpyrifos, O,O-diethyl-O-(3,5,6-trichloro-2-pyridyl phosphorothioate on mosquito fish, Gambusia affinis were carried out in vivo, for 20 days to assess the locomotor behavior in relation to bioaccumulation and interaction with a targeted enzyme, acetylcholinesterase (AChE, EC: 3.1.1.7. Fish exposed to sub-lethal concentration of 60 Ag/L (1/5 of LC50 were under stress, and reduced their locomotor behavior like distance travelled per unit time (m/min and swimming speed (cm/sec with respect to the length of exposure. The alteration in locomotor behavior of fish may be due to an accumulation of acetylcholine (ACh, a neurotransmitter at synaptic junctions, due to the inhibition of AChE enzyme activity (40 to 55% in brain and also bioaccumulation of the toxicant in different parts of fish. The bioaccumulation values indicated that the accumulation of chlorpyrifos was maximum in viscera followed by head and body. The average bioconcentration values are 0.109, 0.009 and 0.004 Ag/g for viscera, head and body with depuration rates of 2.24, 1.69 and 0.39 ng/h respectively. It is evident from the results that the sub-lethal concentration [1/5 of LC50; equivalent to Lowest Observed Effect Concentration (LOEC] of chlorpyrifos can able to alter the locomotor behavior of G. affinis in relation to the length of exposure. The findings revealed that the locomotor activity of test organism could be considered as a suitable marker to evaluate the affect of toxicant even at LOEC levels.

  3. Carbon dots-assisted colorimetric and fluorometric dual-mode protocol for acetylcholinesterase activity and inhibitors screening based on the inner filter effect of silver nanoparticles.

    Zhao, Dan; Chen, Chuanxia; Sun, Jian; Yang, Xiurong

    2016-06-01

    In this work, we proposed an original and versatile dual-readout (colorimetric and fluorometric) protocol by means of silver nanoparticles (AgNPs) and fluorescent carbon dots (CDs), which was amenable to rapid, ultrasensitive assay of acetylcholinesterase (AChE) activity and its inhibitors. The sensing mechanism was based on the non-fluorescence state of CDs resulting from the inner filter effect (IFE) of AgNPs and the specific AChE-catalyzed hydrolysis of acetylthiocholine (ATCh) into thiocholine (TCh). Herein, the generated positively-charged and thiol-bearing TCh at trace concentration levels could trigger the aggregation of AgNPs through the well-known electrostatic and Ag-SH interactions, thereby turning the sensing solutions grey and recovering the IFE-quenched fluorescence simultaneously. Furthermore, the existence of IFE mechanism was conceivably confirmed by combining the zeta potentials, fluorescence spectra, UV-vis spectra, fluorescence lifetime and TEM measurements. As far as we know, the present study has reported the first dual-mode proposal for assessing AChE activity by using a CDs-based IFE sensing strategy, where the detection limit was as low as 0.021 mU mL(-1) and 0.016 mU mL(-1) by colorimetric and fluorometric measurements, respectively. On the other hand, the proposed assay was feasible to screen AChE inhibitors such as tacrine and carbaryl. Meanwhile, this rationally designed dual-mode sensing platform featured simplicity, rapidity, flexibility and diversity, which was demonstrated by the quantitative detection of spiked carbaryl in apple juice samples with satisfactory results. PMID:27099097

  4. Inhibitory activity of root canal irrigants against Candida albicans, Enterococcus faecalis and Staphylococcus aureus

    Tatiana Kelly da Silva Fidalgo; Roberta Barcelos; Maristela Barbosa Portela; Rosangela Maria de Araújo Soares; Rogério Gleiser; Fernando Costa e Silva-Filho

    2010-01-01

    The present study evaluated the antimicrobial activity of three root canal irrigants against Enterococcus faecalis, Candida albicans, and Staphylococcus aureus. These microorganisms were incubated in the presence of citric acid (6 and 10%), EDTA (17%), and NaOCl (0.5, 1.0, 2.5, and 5.25%). Agar diffusion tests were performed and redox indicator resazurin was used to evaluate the inhibitory effect of the irrigants on the metabolic activity of these microorganisms. The mean diameters of the inh...

  5. Acetylcholinesterase activity in the freshwater shrimp Caridina nilotica as a biomarker of Roundup(®) herbicide pollution of freshwater systems in South Africa.

    Mensah, P K; Muller, W J; Palmer, C G

    2012-01-01

    The use of Caridina nilotica whole-body acetylcholinesterase (AChE) activity as a potential biomarker of Roundup(®) pollution of aquatic ecosystems was investigated. Forty days post hatch (dph) shrimps were exposed to different concentrations of 0.0, 4.3, 6.7, 10.5, 16.4, 25.6 and 40.0 mg/L in a 96 h acute toxicity test; and 0.0, 2.2, 2.8, 3.4, 4.3 and 5.4 mg/L in a 21 d chronic toxicity test. Whole-body AChE activities were determined at the end of the exposure periods by spectrophotometric assay of sample extract; activities were then normalized against protein contents in the samples and expressed in nanomoles of substrate hydrolyzed. Results of both tests showed that AChE activity was concentration-dependent. Mean AChE activities and standard deviations (±SD) for 96 h acute toxicity were 3.6239 (± 0.4185), 3.4157 (± 1.1842), 2.537 (± 1.3989), 2.4253 (± 1.4202), 2.4127 (± 1.9097), 2.0017 (± 1.1080) and 2.316 (± 0.4001) nmol/min/mg protein; while activity levels for 21 d test were 3.6907(± 0.3401), 2.8473 (± 0.713), 2.9134 (± 0.9879), 2.6738 (± 0.7117), 2.3019 (± 0.4464) and 2.1478 (± 0.864) nmol/min/mg protein. Reference basal AChE activity for 40 dph C. nilotica based on the two control groups was estimated as 3.6907 (± 0.3401) nmol/min/mg proteins. The present work provides ecotoxicological basis for the possible use of AChE activity in C. nilotica as a biomarker for monitoring Roundup(®) pollution in freshwater systems. PMID:22699346

  6. Trivalent metal ions based on inorganic compounds with in vitro inhibitory activity of matrix metalloproteinase 13.

    Wen, Hanyu; Qin, Yuan; Zhong, Weilong; Li, Cong; Liu, Xiang; Shen, Yehua

    2016-10-01

    Collagenase-3 (MMP-13) inhibitors have attracted considerable attention in recent years and have been developed as a therapeutic target for a variety of diseases, including cancer. Matrix metalloproteinases (MMPs) can be inhibited by a multitude of compounds, including hydroxamic acids. Studies have shown that materials and compounds containing trivalent metal ions, particularly potassium hexacyanoferrate (III) (K3[Fe(CN)6]), exhibit cdMMP-13 inhibitory potential with a half maximal inhibitory concentration (IC50) of 1.3μM. The target protein was obtained by refolding the recombinant histidine-tagged cdMMP-13 using size exclusion chromatography (SEC). The secondary structures of the refolded cdMMP-13 with or without metal ions were further analyzed via circular dichroism and the results indicate that upon binding with metal ions, an altered structure with increased domain stability was obtained. Furthermore, isothermal titration calorimetry (ITC) experiments demonstrated that K3[Fe(CN)6]is able to bind to MMP-13 and endothelial cell tube formation tests provide further evidence for this interaction to exhibit anti-angiogenesis potential. To the best of our knowledge, no previous report of an inorganic compound featuring a MMP-13 inhibitory activity has ever been reported in the literature. Our results demonstrate that K3[Fe(CN)6] is useful as a new effective and specific inhibitor for cdMMP-13 which may be of great potential for future drug screening applications. PMID:27542739

  7. Associations of Physical Activity, Sports Participation and Active Commuting on Mathematic Performance and Inhibitory Control in Adolescents

    Domazet, Sidsel L; Tarp, Jakob; Huang, Tao;

    2016-01-01

    OBJECTIVES: To examine objectively measured physical activity level, organized sports participation and active commuting to school in relation to mathematic performance and inhibitory control in adolescents. METHODS: The design was cross-sectional. A convenient sample of 869 sixth and seventh grade...... students (12-14 years) was invited to participate in the study. A total of 568 students fulfilled the inclusion criteria and comprised the final sample for this study. Mathematic performance was assessed by a customized test and inhibitory control was assessed by a modified Eriksen flanker task. Physical...... level was stratified by bicycling status in order to bypass measurement error subject to the accelerometer. RESULTS: Non-cyclists in the 2nd quartile of counts per minute displayed a higher mathematic score, so did cyclists in the 2nd and 3rd quartile of moderate-to-vigorous physical activity relative...

  8. Antibacterial and EGFR-Tyrosine Kinase Inhibitory Activities of Polyhydroxylated Xanthones from Garcinia succifolia

    Susawat Duangsrisai

    2014-11-01

    Full Text Available Chemical investigation of the methanol extract of the wood of Garcinia succifolia Kurz (Clusiaceae led to the isolation of 1,5-dihydroxyxanthone (1, 1,7-dihydroxyxanthone (2, 1,3,7-trihydroxyxanthone (3, 1,5,6-trihydroxyxanthone (4, 1,6,7-trihydroxyxanthone (5, and 1,3,6,7-tetrahydroxyxanthone (6. All of the isolated xanthones were evaluated for their antibacterial activity against bacterial reference strains, two Gram-positive (Staphylococcus aureus ATTC 25923, Bacillus subtillis ATCC 6633 and two Gram-negative (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853, and environmental drug-resistant isolates (S. aureus B1, Enteroccoccus faecalis W1, and E. coli G1, as well as for their epidermal growth factor receptor (EGFR of tyrosine kinase inhibitory activity. Only 1,5,6-trihydroxy-(4, 1,6,7-trihydroxy-(5, and 1,3,6,7-tetrahydroxyxanthones (6 exhibited antibacterial activity against Gram-positive bacteria, however none was active against vancomycin-resistant E. faecalis. Additionally, 1,7-dihydroxyxanthone (2 showed synergism with oxacillin, but not with ampicillin. On the other hand, only 1,5-dihydroxyxanthone (1 and 1,7-dihydroxyxanthone (2 were found to exhibit the EGFR-tyrosine kinase inhibitory activity, with IC50 values of 90.34 and 223 nM, respectively.

  9. ACE-inhibitory activity of enzymatic protein hydrolysates from lupin and other legumes.

    Boschin, Giovanna; Scigliuolo, Graziana Maria; Resta, Donatella; Arnoldi, Anna

    2014-02-15

    The objective of this investigation was to compare the angiotensin converting enzyme (ACE)-inhibitory activity of the hydrolysates obtained by pepsin digestion of proteins of some legumes, such as chickpea, common bean, lentil, lupin, pea, and soybean, by using the same experimental procedure. The ACE-inhibitory activity was measured by using the tripeptide hippuryl-histidyl-leucine (HHL), as model peptide, and HPLC-DAD, as analytical method. The peptide mixtures of all legumes were active, with soybean and lupin the most efficient, with IC50 values of 224 and 226 μg/ml, respectively. Considering the promising results obtained with lupin, and aiming to identify the protein(s) that release(s) the peptides responsible for the activity, the peptides obtained from the pepsin digestion of some industrial lupin protein isolates and purified protein fractions were tested. The most active mixture, showing an IC50 value of 138 μg/ml, was obtained hydrolysing a mixture of lupin α+β conglutin. PMID:24128446

  10. A Subtype of Inhibitory Interneuron with Intrinsic Persistent Activity in Human and Monkey Neocortex

    Bo Wang

    2015-03-01

    Full Text Available A critical step in understanding the neural basis of human cognitive functions is to identify neuronal types in the neocortex. In this study, we performed whole-cell recording from human cortical slices and found a distinct subpopulation of neurons with intrinsic persistent activity that could be triggered by single action potentials (APs but terminated by bursts of APs. This persistent activity was associated with a depolarizing plateau potential induced by the activation of a persistent Na+ current. Single-cell RT-PCR revealed that these neurons were inhibitory interneurons. This type of neuron was found in different cortical regions, including temporal, frontal, occipital, and parietal cortices in human and also in frontal and temporal lobes of nonhuman primate but not in rat cortical tissues, suggesting that it could be unique to primates. The characteristic persistent activity in these inhibitory interneurons may contribute to the regulation of pyramidal cell activity and participate in cortical processing.

  11. Tyrosinase Inhibitory and Antioxidant Activities of Silk Cocoons and Mulberry Leaves

    Silk cocoons and mulberry leaves have been used in the field of medicines, cosmetics, and foods. The objective of this study is to determine the antioxidant activities of silk cocoons and mulberry leaves using 1,1-diphenyl-2-picryl-hydrazyl radical and thin-layer chromatography (TLC), and to determine tyrosinase inhibitory activities using dihydroxyphenylalanine. The water and ethanol extracts from silk cocoons (Nang Noi, U B1, and Lao) and mulberry leaves showed antioxidants and tyrosinase inhibitory activities. However, the extracts from all samples at 1,000 μg/reaction mixture inhibited tyrosinase in the range of 12.28-45.98%, which was much lower than the standard whitening agent kojic acid (IC50 0.45 μg/reaction mixture). The results from TLC showed that the ethanol extracts from the 3 species of cocoons contained flavonoids, but only the extract from Nang Noi contained carotenoid. In addition, the separation destroyed the fraction with high antioxidant activity. Therefore, the disadvantage of the extract separation is increased cost and decreased antioxidant activities

  12. Effect of the methanol leaves extract of Clinacanthus nutans on the activity of acetylcholinesterase in male mice

    Lau KW

    2014-01-01

    Conclusion: In conclusion, 14 d oral administration of C. nutans was able to modulate cholinergic neurotransmission by activating AChE activity in mice kidney, liver and heart. Compounds that responsible for the induction of AChE activity in mice liver, heart and kidney and its mechanism needs to be elucidated.

  13. Fumonisin concentration and ceramide synthase inhibitory activity of corn, masa, and tortilla chips.

    Voss, Kenneth A; Norred, William P; Meredith, Filmore I; Riley, Ronald T; Stephen Saunders, D

    2006-07-01

    Nixtamalization removes fumonisins from corn and reduces their amounts in masa and tortilla products. Fumonisin concentrations and potential toxicity could be underestimated, however, if unknown but biologically active fumonisins are present. Therefore, the relative amounts of fumonisins in extracts of fumonisin-contaminated corn and its masa and tortilla chip nixtamalization products were determined with an in vitro ceramide synthase inhibition bioassay using increased sphinganine (Sa) and sphinganine to sphingosine ratio (Sa/So) as endpoints. African green monkey kidney cells (Vero cells ATCC CCL-81) were grown in 1-ml wells and exposed to 4 microl of the concentrated extracts for 48 h. The corn extract inhibited ceramide synthase as Sa (mean = 132 pmol/well) and Sa/So (mean = 2.24) were high compared to vehicle controls (Sa = 9 pmol/well; Sa/So = 0.10). Inhibitory activity (mean Sa = 14-24 pmol/well; mean Sa/So = 0.17-0.28) of the masa and tortilla chip extracts were reduced > or = 80% compared to the corn extract. Results were corroborated in a second experiment in which Sa and Sa/So of the wells treated with masa or tortilla chip extracts were reduced > or = 89% compared to those treated with the corn extract. Masa and tortilla chip FB1 concentrations (4-7 ppm) were reduced about 80-90% compared to the corn (30 ppm) when the materials were analyzed by high-performance liquid chromatography (HPLC). Therefore, nixtamalization reduced both the measured amount of FB1 and the ceramide synthase inhibitory activity of masa and tortilla chips extracts. The results further suggest that the masa and tortilla chip extracts did not contain significant amounts of unknown fumonisins having ceramide synthase inhibitory activity. PMID:16760143

  14. Alpha-amylase inhibitory activity and phytochemical study of Zhumeria majdae Rech. f. and Wendelbo

    Behnaz Mirshafie

    2015-01-01

    Full Text Available Background: Zhumeria majdae (Lamiaceae is an endemic species growing in the South parts of Iran especially Hormozgan province. The plant is so-called Mohrekhosh locally and widely used for medicinal purposes including stomachache and dysmenorrhea. Objective: In order to separation and identification of the main flavonoid glycosides of the plant (aerial parts including leaves, stems, flowers, and fruits were used and evaluation of its alpha-amylase inhibitory (AAI activity, methanolic extract was prepared and fractionated to botanolic portion. Materials and Methods: Isolation of the main compounds of the butanol extract of the plant have been performed using different column chromatography methods such as high-performance liquid chromatography (C 18 column and Sephadex LH-20 as well. The isolated compounds were identified by Hydrogen-1 nuclear magnetic resonance and Carbon-13 nuclear magnetic resonance spectra and comparison with those reported in previous literature. Moreover, inhibitory activity of the butanolic extract of the plant against alpha-amylase enzyme was examined in different concentrations (15-30 mg/mL, where acarbose used as a positive control. Results: Three flavonoid glycosides: Linarin (1, hispidulin-7-O-(4-O-acetyl-rutinoside (2, hispidulin-7-O-rutinoside (3 were successfully identified in the extract. The activity of alpha amylase enzyme was dose-dependently suppressed by the butanol extract. The extract exhibited the highest inhibition at 30 mg/mL toward enzyme (77.9 ± 2.1%, while acarbose inhibited the enzyme at 20 mg/mL by 73.9 ± 1.9%. The inhibitory concentrations of 50% for the extract and acarbose were calculated at 24.5 ± 2.1 and 6.6 ± 3.1 mg/mL, respectively. Conclusion: Z. majdae contains glycosylated flavones and could be a good candidate for anti-diabetic evaluations in animal and clinical trials due to possessing AAI activity.

  15. Synthesis of Triazole Schiff’s Base Derivatives and Their Inhibitory Kinetics on Tyrosinase Activity

    Wang, Hui-Fang; Zheng, Jing; Cui, Yi; Fang, Xin-Yu; Zhang, Lin-Min; Chen, Qing-Xi

    2015-01-01

    In the present study, new Schiff’s base derivatives: (Z)-4-amino-5-(2-(3- fluorobenzylidene)hydrazinyl)-4H-1,2,4-triazole-3-thiol (Y1), (Z)-3-((2-(4-amino-5- mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y2), (Z)-2-((2-(4-amino-5- mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y3) and 3-((Z)-(2-(4- (((E)-3-hydroxybenzylidene)amino)-5-mercapto-4H-1,2,4-triazol-3-yl)hydrazono)methyl)phenol (Y4) were synthesized and their structures were characterized by LC-MS, IR and 1H NMR. The inhibitory effects of these compounds on tyrosinase activites were evaluated. Compounds Y1, Y2 and Y3 showed potent inhibitory effects with respective IC50 value of 12.5, 7.0 and 1.5 μM on the diphenolase activities. Moreover, the inhibition mechanisms were determined to be reversible and mixed types. Interactions of the compounds with tyrosinase were further analyzed by fluorescence quenching, copper interaction, and molecular simulation assays. The results together with the anti-tyrosinase activities data indicated that substitution on the second position of benzene ring showed superior ant-ityrosinase activities than that on third position, and that hydroxyl substitutes were better than fluorine substitutes. In addition, two benzene rings connecting to the triazole ring would produce larger steric hindrance, and affect the bonding between tyrosinase and inhibitors to decrease the inhibitory effects. The anti-tyrosinase effects of these compounds were in contrast to their antioxidant activities. In summary, this research will contribute to the development and design of antityrosinase agents. PMID:26422245

  16. Tyrosinase inhibitory effects and antioxidative activities of saponins from Xanthoceras Sorbifolia nutshell.

    Hongmei Zhang

    Full Text Available Certain saponins are bioactive compounds with anticancer, antivirus and antioxidant activities. This paper discussed inhibitory effects of saponins from Xanthoceras Sorbifolia on tyrosinase, through the research of the rate of tyrosinase catalyzed L-DOPA oxidation. The inhibition rate of tyrosinase activity presented non-linear changes with the saponins concentration. The rate reached 52.0% when the saponins concentration was 0.96 mg/ml. Antioxidant activities of saponins from Xanthoceras Sorbifolia were evaluated by using hydroxyl and superoxide radical scavenging assays. The hydroxyl radical scavenging effects of the saponins were 15.5-68.7%, respectively at the concentration of 0.18-2.52 mg/ml. The superoxide radical scavenging activity reduced from 96.6% to 7.05% with the time increasing at the concentration of 1.44 mg/ml. All the above antioxidant evaluation indicated that saponins from Xanthoceras Sorbifolia exhibited good antioxidant activity in a concentration- dependent manner.

  17. Angiotensin-converting enzyme inhibitory activity of milk fermented by wild and industrial Lactococcus lactis strains.

    Rodríguez-Figueroa, J C; Reyes-Díaz, R; González-Córdova, A F; Troncoso-Rojas, R; Vargas-Arispuro, I; Vallejo-Cordoba, B

    2010-11-01

    Angiotensin I-converting enzyme inhibitory (ACEI) activity was evaluated and compared in milk fermented by wild and commercial starter culture Lactococcus lactis strains after 48 h of incubation. The highest ACEI activities were found in WSE from milk inoculated with wild L. lactis strains isolated from artisanal dairy products and commercial starter cultures. On the other hand, the lowest ACEI activities were found in WSE from milk inoculated with wild strains isolated from vegetables. Moreover, the IC(50) values (concentration that inhibits 50% activity) of WSE from artisanal dairy products were the lowest, indicating that these fractions were the most effective in inhibiting 50% of ACE activity. In fact, a strain isolated from artisanal cheese presented the lowest IC(50) (13 μg/mL). Thus, it appears that wild L. lactis strains isolated from artisanal dairy products and commercial starter cultures showed good potential for the production of fermented dairy products with ACEI properties. PMID:20965317

  18. In Vitro Screening of Medicinal Plants Used in Mexico as Antidiabetics with Glucosidase and Lipase Inhibitory Activities

    Guillermo Ramírez; Miguel Zavala; Julia Pérez; Alejandro Zamilpa

    2012-01-01

    This work shows the inhibitory effect on glucosidase and lipase enzymes of 23 medicinal plants described as traditional treatments for diabetes in several Mexican sources. Hydroalcoholic extracts of selected plants were evaluated at 1 mg/mL for glucosidase and 0.25 mg/mL for lipase inhibitory activities, respectively. Camellia sinensis, acarbose, and orlistat were used as positive controls. Dose-response curves were done with the most active species. Sixty percent of all tested extracts inhib...

  19. Nanocapsular Dispersion of Cinnamaldehyde for Enhanced Inhibitory Activity against Aflatoxin Production by Aspergillus flavus

    Hongbo Li

    2015-04-01

    Full Text Available Cinnamaldehyde (CA is marginally soluble in water, making it challenging to evenly disperse it in foods, and resulting in lowered anti-A. flavus efficacy. In the present study, nano-dispersed CA (nano-CA was prepared to increase its aqueous solubility. Free and nano-dispersed CA were compared in terms of their inhibitory activity against fungal growth and aflatoxin production of A. flavus both in Sabouraud Dextrose (SD culture and in peanut butter. Our results indicated that free CA inhibited the mycelia growth and aflatoxin production of A. flavus with a minimal inhibitory concentration (MIC value of 1.0 mM, but promoted the aflatoxin production at some concentrations lower than the MIC. Nano-CA had a lower MIC value of 0.8 mM against A. flavus, and also showed improved activity against aflatoxin production without the promotion at lower dose. The solidity of peanut butter had an adverse impact on the antifungal activity of free CA, whereas nano-dispersed CA showed more than 2-fold improved activity against the growth of A. flavus. Free CA still promoted AFB1 production at the concentration of 0.25 mM, whereas nano-CA showed more efficient inhibition of AFB1 production in the butter.

  20. Repressors report fewer intrusions following a laboratory stressor: the role of reduced stressor-relevant concept activation and inhibitory functioning.

    Overwijk, Sippie; Wessel, Ineke; de Jong, Peter J

    2009-03-01

    This study investigated whether a repressive coping style is associated with fewer intrusions following an experimentally controlled stressor. Furthermore, we examined whether lower activation of stressor-relevant concepts in long-term memory and better inhibitory functioning may contribute to this association. Extreme-scoring participants on a trait anxiety and a social desirability scale were selected to form repressor (n=35), low anxious (n=15), high anxious (n=30), and defensive (n=21) groups. In line with predictions, repressors reported fewer intrusions following a failure manipulation compared to non-repressors. Furthermore, pre-stressor inhibitory functioning was negatively associated with color-naming interference of stressor-related words. This suggests that overall, higher inhibitory control is related to lower activation of failure-related concepts. However, there was no evidence that concept activation and inhibitory control were responsible for repressors' lower number of self-reported intrusions. PMID:18937086

  1. Synthesis and CDK2 kinase inhibitory activity of 7/7′-azaindirubin derivatives

    2010-01-01

    A series of novel 7'-azaindirubin(1a-g) and 7-azaindirubin(2a,2c,2e and 2f) derivatives were designed and synthesized.Their structures were characterized by ~1H NMR and MS spectroscopy as well as by elemental analysis.Their inhibitory properties against CDK2/cylinA were evaluated in vitro.In contrast to indirubin,some of the described azaindirubins emerged as potent inhibitors of CDK2/cylinA and compound 2b had more potent activity.Biological tests also showed that nitrogen atom at 7-position of azaindir...

  2. Inhibitory effect of mycoplasma-released arginase. Activity in mixed-lymphocyte and tumour cell cultures

    Claesson, M H; Tscherning, T; Nissen, Mogens Holst; Lind, K

    1990-01-01

    inhibition can be reversed by addition of excess arginine to the culture medium. Antisera raised against non-fermenting, but not against fermenting, mycoplasma species block the inhibitory effect of MAE. SDS-PAGE separation of MAE disclosed a broad band at 60 kDa which contained arginase activity when...... assayed in MLC and cell proliferation culture. SDS-PAGE followed by western blotting and reaction with antisera raised against non-fermenting mycoplasma species demonstrated a band at 43 kDa common for these micro-organisms....

  3. Xanthones from the Botanical Dietary Supplement Mangosteen (Garcinia mangostana) with Aromatase Inhibitory Activity

    Balunas, Marcy J.; Su, Bin; Brueggemeier, Robert W.; Kinghorn, A. Douglas

    2008-01-01

    Twelve xanthone constituents of the botanical dietary supplement, mangosteen (the pericarp of Garcinia mangostina) were screened using a non-cellular, enzyme-based microsomal aromatase inhibition assay. Of these compounds, garcinone D (3), garcinone E (5)α-mangostin (8), and γ-mangostin (9) exhibited dose-dependent inhibitory activity. In a follow-up cell-based assay using SK-BR-3 breast cancer cells that express high levels of aromatase, the most potent of these four xanthones was γ-mangosti...

  4. In silico approach for alpha-amylase inhibitory activity of diosmetin and galangin

    Arumugam Madeswaran; Kuppusamy Asokkumar; Muthuswamy Umamaheswari; Thirumalaisamy Sivashanmugam; Varadharajan Subhadradevi

    2014-01-01

    Objective: The objective of the current study is to evaluate the α-amylase inhibitory activity of diosmetin and galangin using in silico docking studies.Methods: In this perspective, diosmetin and galangin were prepared for the docking evaluation. Acarbose, a known α-amylase inhibitor was used as the standard. In silico docking studies were carried out using recent version of AutoDock 4.2, which has the basic principle of Lamarckian genetic algorithm.Results: The results showed that the selec...

  5. Preliminary pharmacological studies on Eugenia uniflora leaves: xanthine oxidase inhibitory activity.

    Schmeda-Hirschmann, G; Theoduloz, C; Franco, L; Ferro, E; de Arias, A R

    1987-11-01

    Eugenia uniflora is widely used in Paraguayan folk medicine. A hydroalcoholic extract of the leaves showed some central nervous system activity in hippocratic screening when given intraperitoneally, but little to no acute or subacute toxicity in doses up to 4200 mg/kg orally in BALB c mice. The LD50 of the extract was 220 mg/kg i.p. in mice. A decoction or infusion of the leaves is recommended for treating gout by native herbalists. The known flavonoids quercitrin, quercetin, myricitrin and myricetin were found to be responsible for the xanthine oxidase inhibitory action of the plant extract. PMID:3437769

  6. Lactobacillus crispatus dominant vaginal microbiome is associated with inhibitory activity of female genital tract secretions against Escherichia coli.

    Jeny P Ghartey

    Full Text Available OBJECTIVE: Female genital tract secretions inhibit E. coli ex vivo and the activity may prevent colonization and provide a biomarker of a healthy microbiome. We hypothesized that high E. coli inhibitory activity would be associated with a Lactobacillus crispatus and/or jensenii dominant microbiome and differ from that of women with low inhibitory activity. STUDY DESIGN: Vaginal swab cell pellets from 20 samples previously obtained in a cross-sectional study of near-term pregnant and non-pregnant healthy women were selected based on having high (>90% inhibition or low (<20% inhibition anti-E. coli activity. The V6 region of the 16S ribosomal RNA gene was amplified and sequenced using the Illumina HiSeq 2000 platform. Filtered culture supernatants from Lactobacillus crispatus, Lactobacillus iners, and Gardnerella vaginalis were also assayed for E. coli inhibitory activity. RESULTS: Sixteen samples (10 with high and 6 with low activity yielded evaluable microbiome data. There was no difference in the predominant microbiome species in pregnant compared to non-pregnant women (n = 8 each. However, there were significant differences between women with high compared to low E. coli inhibitory activity. High activity was associated with a predominance of L. crispatus (p<0.007 and culture supernatants from L. crispatus exhibited greater E. coli inhibitory activity compared to supernatants obtained from L. iners or G. vaginalis. Notably, the E. coli inhibitory activity varied among different strains of L. crispatus. CONCLUSION: Microbiome communities with abundant L. crispatus likely contribute to the E. coli inhibitory activity of vaginal secretions and efforts to promote this environment may prevent E. coli colonization and related sequelae including preterm birth.

  7. Oxidative stress and damage to erythrocytes in patients with chronic obstructive pulmonary disease--changes in ATPase and acetylcholinesterase activity.

    Bukowska, Bożena; Sicińska, Paulina; Pająk, Aneta; Koceva-Chyla, Aneta; Pietras, Tadeusz; Pszczółkowska, Anna; Górski, Paweł; Koter-Michalak, Maria

    2015-12-01

    The study indicates, for the first time, the changes in both ATPase and AChE activities in the membrane of red blood cells of patients diagnosed with COPD. Chronic obstructive pulmonary disease (COPD) is one of the most common and severe lung disorders. We examined the impact of COPD on redox balance and properties of the membrane of red blood cells. The study involved 30 patients with COPD and 18 healthy subjects. An increase in lipid peroxidation products and a decrease in the content of -SH groups in the membrane of red blood cells in patients with COPD were observed. Moreover, an increase in the activity of glutathione peroxidase and a decrease in superoxide dismutase, but not in catalase activity, were found as well. Significant changes in activities of erythrocyte membrane enzymes in COPD patients were also evident demonstrated by a considerably lowered ATPase activity and elevated AChE activity. Changes in the structure and function of red blood cells observed in COPD patients, together with changes in the activity of the key membrane enzymes (ATPases and AChE), can result from the imbalance of redox status of these cells due to extensive oxidative stress induced by COPD disease. PMID:26369587

  8. Inhibitory activity of Iranian plant extracts on growth and biofilm formation by Pseudomonas aeruginosa

    Mansouri, S.

    2013-01-01

    Full Text Available Aims: Pseudomonas aeruginosa is a drug resistance opportunistic bacterium. Biofilm formation is key factor for survivalof P. aeruginosa in various environments. Polysaccharides may be involved in biofilm formation. The purpose of thisstudy was to evaluate antimicrobial and anti-biofilm activities of seven plant extracts with known alpha-glucosidaseinhibitory activities on different strains of P. aeruginosa.Methodology and results: Plants were extracted with methanol by the maceration method. Antimicrobial activities weredetermined by agar dilution and by growth yield as measured by OD560nm of the Luria Bertani broth (LB culture with orwithout extracts. In agar dilution method, extracts of Quercus infectoria inhibited the growth of all, while Myrtuscommunis extract inhibited the growth of 3 out of 8 bacterial strains with minimum inhibitory concentration (MIC of 1000μg/mL. All extracts significantly (p≤0.003 reduced growth rate of the bacteria in comparison with the control withoutextracts in LB broth at sub-MIC concentrations (500 μg/mL. All plant extracts significantly (p≤0.003 reduced biofilmformation compared to the controls. Glycyrrhiza glabra and Q. infectoria had the highest anti-biofilm activities. Nocorrelation between the alpha-glucosidase inhibitory activity with growth or the intensity of biofilm formation was found.Conclusion, significance and impact of study: Extracts of Q. infectoria and M. communis had the most antimicrobial,while Q. infectoria and G. glabra had the highest anti-biofilm activities. All plant extracts had anti-biofilm activities withmarginal effect on growth, suggesting that the mechanisms of these activities are unrelated to static or cidal effects.Further work to understand the relation between antimicrobial and biofilm formation is needed for development of newmeans to fight the infectious caused by this bacterium in future.

  9. Expression and inhibitory activity analysis of a 25-kD Bowman-Birk protease inhibitor in rice

    2006-01-01

    Rice Bowman-Birk inhibitors (RBBI), with one (8 kD) or two homologous domains (16 kD), were found to be effective trypsin inhibitors in vitro. In this study, we demonstrate that the 25-kD protein corresponding to the three-domain RBBI indeed exists in rice in planta, and that the RBBIs are regulated by development and wounding. We also found by inhibitory activity assay that the 3:13 disulfide bond, but not the 4:5 disulfide bond, suppresses the trypsin-inhibitory activity, and the D3 domain of RBBI3-1 has no inhibitory activity against trypsin, chymotrypsin, paparin or subtilisin. Mutation analyses showed that conversion from Lys to Leu or Tyr in the N-terminal P1 site in D1 domain did not create chymotrypsin-inhibitory activity, suggesting that the structure of the reactive loop in D1 domain hinder the new inhibitory specificity at P1 site, and the chymotrypsin-inhibitory activity might need the participation of other structures, e.g. 3:13 disulfide bond.

  10. Hypocholesterolemic Effect and In Vitro Pancreatic Lipase Inhibitory Activity of an Opuntia ficus-indica Extract.

    Padilla-Camberos, Eduardo; Flores-Fernandez, Jose Miguel; Fernandez-Flores, Ofelia; Gutierrez-Mercado, Yanet; Carmona-de la Luz, Joel; Sandoval-Salas, Fabiola; Mendez-Carreto, Carlos; Allen, Kirk

    2015-01-01

    Cholesterol control is fundamental for prevention of cardiovascular disorders. In this work, the hypocholesterolemic activity of an aqueous Opuntia ficus-indica extract (AOE) was tested in triton-induced mice. The inhibitory activity on pancreatic lipase enzyme was evaluated in vitro by the same extract. Furthermore, polyphenol content of the extract was evaluated. Hypercholesterolemia was induced in three groups of mice by intraperitoneal administration of Triton WR-1339. After induction of hypercholesterolemia, the groups were treated with an AOE (500 mg/kg) and saline solution and the positive control group with orlistat, respectively. Cholesterol levels were measured 24 h later in peripheral blood. The levels of blood cholesterol after administration of AOE significantly decreased compared to negative control. The inhibitory activity of AOE on pancreatic lipase enzyme was evaluated at concentrations from 60 to 1000 μg/mL. The AOE inhibited the pancreatic lipase with an IC50 = 588.5 μg/mL. The AOE had a high content of polyphenolic compounds. These results show that AOE is able to prevent hypercholesterolemia by pancreatic lipase inhibition, in part due to its polyphenolic compounds. PMID:26078966

  11. Hypocholesterolemic Effect and In Vitro Pancreatic Lipase Inhibitory Activity of an Opuntia ficus-indica Extract

    Eduardo Padilla-Camberos

    2015-01-01

    Full Text Available Cholesterol control is fundamental for prevention of cardiovascular disorders. In this work, the hypocholesterolemic activity of an aqueous Opuntia ficus-indica extract (AOE was tested in triton-induced mice. The inhibitory activity on pancreatic lipase enzyme was evaluated in vitro by the same extract. Furthermore, polyphenol content of the extract was evaluated. Hypercholesterolemia was induced in three groups of mice by intraperitoneal administration of Triton WR-1339. After induction of hypercholesterolemia, the groups were treated with an AOE (500 mg/kg and saline solution and the positive control group with orlistat, respectively. Cholesterol levels were measured 24 h later in peripheral blood. The levels of blood cholesterol after administration of AOE significantly decreased compared to negative control. The inhibitory activity of AOE on pancreatic lipase enzyme was evaluated at concentrations from 60 to 1000 μg/mL. The AOE inhibited the pancreatic lipase with an IC50 = 588.5 μg/mL. The AOE had a high content of polyphenolic compounds. These results show that AOE is able to prevent hypercholesterolemia by pancreatic lipase inhibition, in part due to its polyphenolic compounds.

  12. Effects of nanosuspension and inclusion complex techniques on the in vitro protease inhibitory activity of naproxen

    Dharmalingam, Senthil Rajan; Chidambaram, Kumarappan; Srinivasan, Ramamurthy; Nadaraju, Shamala, E-mail: dsenthilrajan@yahoo.co.in [School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur (Malaysia)

    2014-01-15

    This study investigated the effects of nanosuspension and inclusion complex techniques on in vitro trypsin inhibitory activity of naproxen—a member of the propionic acid derivatives, which are a group of antipyretic, analgesic, and non-steroidal anti-inflammatory drugs. Nanosuspension and inclusion complex techniques were used to increase the solubility and anti-inflammatory efficacy of naproxen. The evaporative precipitation into aqueous solution (EPAS) technique and the kneading methods were used to prepare the nanosuspension and inclusion complex of naproxen, respectively. We also used an in vitro protease inhibitory assay to investigate the anti-inflammatory effect of modified naproxen formulations. Physiochemical properties of modified naproxen formulations were analyzed using UV, IR spectra, and solubility studies. Beta-cyclodextrin inclusion complex of naproxen was found to have a lower percentage of antitryptic activity than a pure nanosuspension of naproxen did. In conclusion, nanosuspension of naproxen has a greater anti-inflammatory effect than the other two tested formulations. This is because the nanosuspension formulation reduces the particle size of naproxen. Based on these results, the antitryptic activity of naproxen nanosuspension was noteworthy; therefore, this formulation can be used for the management of inflammatory disorders. (author)

  13. Spectroscopic studies on the inhibitory effects of ionic liquids on lipase activity

    Fan, Yunchang; Dong, Xing; Li, Xiaojing; Zhong, Yingying; Kong, Jichuan; Hua, Shaofeng; Miao, Juan; Li, Yan

    2016-04-01

    The effects of ionic liquids (ILs) on the lipase activity were studied by UV-Vis spectroscopy and the IL-lipase interaction mechanism at the molecular level was investigated by fluorescence technique. Experimental results indicated that the lipase activity was inhibited by ILs and the degree of inhibition highly depended on the chemical structures of ILs. The inhibitory ability of the Cl-- and Br--based ILs increased with increasing the alkyl chain length in the IL cation. Thermodynamic parameters, enthalpy change (ΔH) and entropy change (ΔS) were obtained by analyzing the fluorescence behavior of lipase with the addition of ILs. Both ΔH and ΔS were positive suggesting hydrophobicity was the major driven force for the Cl-- and Br--based ILs. For the BF4--, CF3SO3--, ClO4-- and N(CN)2--based ILs, hydrogen bonding was the main driven force. For a more comprehensive understanding of the effects of ILs on lipase activity, the roles of hydrophobicity and hydrogen bonding must be considered simultaneously. A regression-based equation was developed to describe the relationship of the inhibitory ability of ILs and their hydrophobicity and hydrogen bonding ability.

  14. The Dynamics of Ligand Barrier Crossing Inside the Acetylcholinesterase Gorge

    Bui, Jennifer M.(University of California, San Diego); Henchman, Richard H.(University of California, San Diego); Mccammon, Andy (University of California, San Diego)

    2003-10-01

    The dynamics of ligand movement through the constricted region of the acetylcholinesterase gorge is important in understanding how the ligand gains access to and is released from the active site of the enzyme. Molecular dynamics simulations of the simple ligand, tetramethylammonium, crossing this bottleneck region are conducted using umbrella potential sampling and activated .ux techniques. The low potential of mean force obtained is consistent with the fast reaction rate of acetylcholinesterase observed experimentally. From the results of the activated dynamics simulations, local conformational .uctuations of the gorge residues and larger scale collective motions of the protein are found to correlate highly with the ligand crossing.

  15. Kinetics of acetylcholinesterase inhibition by an aqueous extract of Cuminum cyminum seeds

    Suresh Kumar

    2014-03-01

    Full Text Available The cholinergic hypothesis of Alzheimer’s disease (AD has provided the rationale for the current pharmacotherapy of this disease. Acetylcholinesterase (AChE inhibitors are currently the only approved therapy for the symptomatic treatment of AD. The current drugs available in the market has shown various side effect which prompted scientist to search for new and potent AChE inhibitors which exerts minimal side effect in AD patient. In present study, an aqueous extract of Cumin cyminum was tested for in vitro acetylcholinesterase inhibitory activity based on Ellman’s method. C. cyminum showed maximum inhibition of 76.90±0.003% in an aqueous extract at 50μg/ml final concentration. Further studies were conducted to elucidate the mode of AChE inhibition by kinetic studies. Competitive inhibition was observed at lower concentrations (12.5μg/ml & 25μg/ml and mixed inhibition was observed at higher concentrations (50μg/ml & 100μg/ml.

  16. A novel biosensor method for surfactant determination based on acetylcholinesterase inhibition

    A novel enzyme biosensor based on acetylcholinesterase inhibition for the determination of surfactants in aqueous solutions is described. Acetylcholinesterase-based bioselective element was deposited via glutaraldehyde on the surface of conductometric transducers. Different variants of inhibitory analysis of surfactants were tested, and finally surfactant's concentration was evaluated by measuring initial rate of acetylcholinesterase inhibition. Besides, we studied the effect of solution characteristics on working parameters of the biosensor for direct measurement of acetylcholine and for inhibitory determination of surfactants. The biosensor's sensitivity to anionic and cationic surfactants (0.35 mg l−1) was tested. The high operational stability of the biosensor during determination of acetylcholine (RSD 2%) and surfactants (RSD 11%) was shown. Finally, we discussed the selectivity of the biosensor toward surfactants and other AChE inhibitors. The proposed biosensor can be used as a component of the multibiosensor for ecological monitoring of toxicants. (paper)

  17. A novel biosensor method for surfactant determination based on acetylcholinesterase inhibition

    Kucherenko, I. S.; Soldatkin, O. O.; Arkhypova, V. M.; Dzyadevych, S. V.; Soldatkin, A. P.

    2012-06-01

    A novel enzyme biosensor based on acetylcholinesterase inhibition for the determination of surfactants in aqueous solutions is described. Acetylcholinesterase-based bioselective element was deposited via glutaraldehyde on the surface of conductometric transducers. Different variants of inhibitory analysis of surfactants were tested, and finally surfactant's concentration was evaluated by measuring initial rate of acetylcholinesterase inhibition. Besides, we studied the effect of solution characteristics on working parameters of the biosensor for direct measurement of acetylcholine and for inhibitory determination of surfactants. The biosensor's sensitivity to anionic and cationic surfactants (0.35 mg l-1) was tested. The high operational stability of the biosensor during determination of acetylcholine (RSD 2%) and surfactants (RSD 11%) was shown. Finally, we discussed the selectivity of the biosensor toward surfactants and other AChE inhibitors. The proposed biosensor can be used as a component of the multibiosensor for ecological monitoring of toxicants.

  18. Inhibitory effect of some tropical green leafy vegetables on key enzymes linked to Alzheimer’s disease and some pro-oxidant induced lipid peroxidation in rats’ brain

    Oboh, Ganiyu; Akinyemi, Ayodele Jacobson; Ademiluyi, Adedayo Oluwaseun; Bello, Fatai Olumide

    2011-01-01

    This study sought to investigate the inhibitory effect of some commonly consumed Nigerian green leafy vegetables (raw and blanched) on acetylcholinesterase and butyrylcholinesterase (key enzyme linked to Alzheimer’s disease) activities and some pro-oxidants (FeSO4, Sodium nitroprusside and Quinolinic acid) induced lipid peroxidation in rat brain in vitro. Three commonly consumed green leafy vegetables in Nigeria [Amarantus cruentus (Arowojeja), Struchium sparganophora (Ewuro-odo) and Telfairi...

  19. Inhibitory effect of aqueous dandelion extract on HIV-1 replication and reverse transcriptase activity

    Han Huamin

    2011-11-01

    Full Text Available Abstract Background Acquired immunodeficiency syndrome (AIDS, which is caused by the human immunodeficiency virus (HIV, is an immunosuppressive disease that results in life-threatening opportunistic infections. The general problems in current therapy include the constant emergence of drug-resistant HIV strains, adverse side effects and the unavailability of treatments in developing countries. Natural products from herbs with the abilities to inhibit HIV-1 life cycle at different stages, have served as excellent sources of new anti-HIV-1 drugs. In this study, we aimed to investigate the anti-HIV-1 activity of aqueous dandelion extract. Methods The pseudotyped HIV-1 virus has been utilized to explore the anti-HIV-1 activity of dandelion, the level of HIV-1 replication was assessed by the percentage of GFP-positive cells. The inhibitory effect of the dandelion extract on reverse transcriptase activity was assessed by the reverse transcriptase assay kit. Results Compared to control values obtained from cells infected without treatment, the level of HIV-1 replication and reverse transcriptase activity were decreased in a dose-dependent manner. The data suggest that dandelion extract has a potent inhibitory activity against HIV-1 replication and reverse transcriptase activity. The identification of HIV-1 antiviral compounds from Taraxacum officinale should be pursued. Conclusions The dandelion extract showed strong activity against HIV-1 RT and inhibited both the HIV-1 vector and the hybrid-MoMuLV/MoMuSV retrovirus replication. These findings provide additional support for the potential therapeutic efficacy of Taraxacum officinale. Extracts from this plant may be regarded as another starting point for the development of an antiretroviral therapy with fewer side effects.

  20. Data on synthesis of methylene bisphosphonates and screening of their inhibitory activity towards HIV reverse transcriptase.

    Yanvarev, D V; Korovina, A N; Usanov, N N; Khomich, O A; Vepsäläinen, J; Puljula, E; Kukhanova, M K; Kochetkov, S N

    2016-09-01

    Inorganic pyrophosphate (PPi) mimetics designed on a basis of methylenediphosphonic acid backbone are promising inhibitors of two key HIV replication enzymes, IN [1] and RT [2]. Herein, we present chemical synthesis of eleven methylenebisphosphonates (BPs) with their NMR and HRMS analysis synthesized via five different ways. Also, we present data on inhibition of HIV RT catalyzed phosphorolysis and polymerization by synthesized BPs using two methods based on denaturing urea PAGE. Tests were also performed for thymidine analogue mutations reverse transcriptase (TAM RT), which was expressed and purified for that. Structure-activity relationships and inhibitory activity data of synthesized BPs are presented in "Methylene bisphosphonates as the inhibitors of HIV RT phosphorolytic activity" [2]. PMID:27547792

  1. The effects of inhibitory control training for preschoolers on reasoning ability and neural activity.

    Liu, Qian; Zhu, Xinyi; Ziegler, Albert; Shi, Jiannong

    2015-01-01

    Inhibitory control (including response inhibition and interference control) develops rapidly during the preschool period and is important for early cognitive development. This study aimed to determine the training and transfer effects on response inhibition in young children. Children in the training group (N = 20; 12 boys, mean age 4.87 ± 0.26 years) played "Fruit Ninja" on a tablet computer for 15 min/day, 4 days/week, for 3 weeks. Children in the active control group (N = 20; 10 boys, mean age 4.88 ± 0.20 years) played a coloring game on a tablet computer for 10 min/day, 1-2 days/week, for 3 weeks. Several cognitive tasks (involving inhibitory control, working memory, and fluid intelligence) were used to evaluate the transfer effects, and electroencephalography (EEG) was performed during a go/no-go task. Progress on the trained game was significant, while performance on a reasoning task (Raven's Progressive Matrices) revealed a trend-level improvement from pre- to post-test. EEG indicated that the N2 effect of the go/no-go task was enhanced after training for girls. This study is the first to show that pure response inhibition training can potentially improve reasoning ability. Furthermore, gender differences in the training-induced changes in neural activity were found in preschoolers. PMID:26395158

  2. Phenolic composition, antioxidant and enzyme inhibitory activities of Eryngium bornmuelleri leaf.

    Dalar, Abdullah; Türker, Musa; Zabaras, Dimitrios; Konczak, Izabela

    2014-03-01

    Eryngium bornmuelleri Nab. (Tusî) is an endemic botanical from the Eastern Anatolia region of Turkey traditionally used for preparation of herbal tea. Within this study, phenolic composition, antioxidant capacities and inhibitory activities towards selected digestive enzymes of E. bornmuelleri leaf were investigated. Sequential extracts, obtained by extraction of plant tissue by ethanol, acetone and water exhibited pronounced antioxidant capacities and in a dose-dependent manner suppressed the metabolic syndrome related enzymes: α-amylase, α-glucosidase and pancreatic lipase. All extracts contained high levels of phenolic compounds. Flavonoid glycosides were the main phytochemicals detected, with rutin as the major compound (70% of total phenolics). Chlorogenic, hydroxybenzoic and caftaric acids as well as traces of caffeic, ferulic and rosmarinic acids were also detected. Correlation analysis indicated that phenolic compounds were the major sources of the enzyme-inhibitory activities. This study suggests that E. bornmuelleri leaf extracts can modulate the metabolism of sugars and fats through inhibition of the relevant digestive enzymes. PMID:24202545

  3. Antioxidant activity and ACE-inhibitory of Class II hydrophobin from wild strain Trichoderma reesei.

    Khalesi, Mohammadreza; Jahanbani, Raheleh; Riveros-Galan, David; Sheikh-Hassani, Vahid; Sheikh-Zeinoddin, Mahmoud; Sahihi, Mehdi; Winterburn, James; Derdelinckx, Guy; Moosavi-Movahedi, Ali Akbar

    2016-10-01

    There are several possible uses of the Class II hydrophobin HFBII in clinical applications. To fully understand and exploit this potential however, the antioxidant activity and ACE-inhibitory potential of this protein need to be better understood and have not been previously reported. In this study, the Class II hydrophobin HFBII was produced by the cultivation of wild type Trichoderma reesei. The crude hydrophobin extract obtained from the fermentation process was purified using reversed-phase liquid chromatography and the identity of the purified HFBII verified by MALDI-TOF (molecular weight: 7.2kDa). Subsequently the antioxidant activities of different concentrations of HFBII (0.01-0.40mg/mL) were determined. The results show that for HFBII concentrations of 0.04mg/mL and upwards the protein significantly reduced the presence of ABTS(+) radicals in the medium, the IC50 value found to be 0.13mg/mL. Computational modeling highlighted the role of the amino acid residues located in the conserved and exposed hydrophobic patch on the surface of the HFBII molecule and the interactions with the aromatic rings of ABTS. The ACE-inhibitory effect of HFBII was found to occur from 0.5mg/mL and upwards, making the combination of HFBII with strong ACE-inhibitors attractive for use in the healthcare industry. PMID:27211298

  4. Acid-sensing ion channels regulate spontaneous inhibitory activity in the hippocampus: possible implications for epilepsy.

    Ievglevskyi, O; Isaev, D; Netsyk, O; Romanov, A; Fedoriuk, M; Maximyuk, O; Isaeva, E; Akaike, N; Krishtal, O

    2016-08-01

    Acid-sensing ion channels (ASICs) play an important role in numerous functions in the central and peripheral nervous systems ranging from memory and emotions to pain. The data correspond to a recent notion that each neuron and many glial cells of the mammalian brain express at least one member of the ASIC family. However, the mechanisms underlying the involvement of ASICs in neuronal activity are poorly understood. However, there are two exceptions, namely, the straightforward role of ASICs in proton-based synaptic transmission in certain brain areas and the role of the Ca(2+)-permeable ASIC1a subtype in ischaemic cell death. Using a novel orthosteric ASIC antagonist, we have found that ASICs specifically control the frequency of spontaneous inhibitory synaptic activity in the hippocampus. Inhibition of ASICs leads to a strong increase in the frequency of spontaneous inhibitory postsynaptic currents. This effect is presynaptic because it is fully reproducible in single synaptic boutons attached to isolated hippocampal neurons. In concert with this observation, inhibition of the ASIC current diminishes epileptic discharges in a low Mg(2+) model of epilepsy in hippocampal slices and significantly reduces kainate-induced discharges in the hippocampus in vivo Our results reveal a significant novel role for ASICs.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377725

  5. ACE-I Inhibitory Activity from Phaseolus lunatus and Phaseolus vulgaris Peptide Fractions Obtained by Ultrafiltration.

    Betancur-Ancona, David; Dávila-Ortiz, Gloria; Chel-Guerrero, Luis Antonio; Torruco-Uco, Juan Gabriel

    2015-11-01

    The involvement of angiotensin-I-converting enzyme (ACE-I) as one of the mechanisms controlling blood pressure is being studied to find alternative means of control of hypertension on human beings. On the market there are synthetic drugs that can control it, but these can cause undesirable health side effects. In this work was assessed the fractionation by ultrafiltration of the Lima bean (Phaseolus lunatus) and Jamapa bean (Phaseolus vulgaris), protein hydrolysates obtained with Alcalase(®) and Flavourzyme(®) on ACE-I inhibitory activity. Four membranes of different molecular cutoffs (10, 5, 3, and 1 kDa) were used. Fractions that had a higher inhibitory activity in both legumes were denominated as E (Alcalase and Flavourzyme, respectively, and for the Phaseolus vulgaris with Alcalase and Flavourzyme with about 63.8 and 65.8 μg/mL values, respectively. The amino acid composition of these fractions showed residues in essential amino acids, which make a good source of energy and amino acids. On the other hand, the presence of hydrophobic amino acids such as V and P is a determining factor in the ACE-I inhibitor effect. The results suggest the possibility of obtaining and utilizing these peptide fractions in the development and innovation of a functional product that helps with treatment and/or prevention of hypertension. PMID:26061663

  6. 2-(2-Pyridyl) Benzimidazole Analogs and their beta-Glucuronidase Inhibitory Activity

    Synthesis of 2-(2-Pyridyl) benzimidazole analogs 1-11 have been carried out and evaluated for in vitro beta-glucuronidase inhibitory potential. The compounds 4 (IC/sub 50/ = 4.06 ± 0.34 meuM), 5 (IC/sub 50/ = 09.63 ± 0.81 meuM), 1 (IC/sub 50/ = 19.66 ± 0.44 meuM), 7 (IC/sub 50/ = 24.75 ± 0.25 meuM), 6 (IC/sub 50/ = 26.30 ± 1.37 meuM), and 3 (IC/sub 50/ = 32.11 ± 0.89 meuM), showed beta-glucuronidase inhibitory activity superior to the standard D-saccharic acid 1,4-lactone, with (IC/sub 50/ = 48.4 ± 1.25 meuM). Based on structure-activity relationship, we discover a new class of potent beta-glucuronidase inhibitors. (author)

  7. In Silico Docking studies of Aldose Reductase Inhibitory activity of selected Flavonoids

    Muthuswamy Umamaheswari

    2012-09-01

    Full Text Available New drugs for the inhibition of the enzyme aldose reductase are in development and they have to be screened before being considered for preclinical and clinical evaluation. The current study deals with the evaluation of the cyclooxygenase inhibitory activity of flavonoids using in silico docking studies. In this perspective, flavonoids like Farobin-A, Gericudranin- B, Glaziovianin-A, Rutin, and Xanthotoxin were selected. Epalrestat, a known aldose reductase inhibitor was used as the standard. Docking results showed that all the selected flavonoids showed binding energy ranging between -7.91 kcal/mol to - 5.08 kcal/mol when compared with that of the standard (-5.59 kcal/mol. Intermolecular energy (- 9.11 kcal/mol to -8.66 kcal/mol and inhibition constant (1.58 μM to 187.37 μM of the ligands also coincide with the binding energy. Xanthotoxin contributed better aldose reductase inhibitory activity because of its structural parameters. Further studies are required to develop potent aldose reductase inhibitors for the treatment of diabetes.

  8. In silico approach for alpha-amylase inhibitory activity of diosmetin and galangin

    Arumugam Madeswaran

    2014-10-01

    Full Text Available Objective: The objective of the current study is to evaluate the α-amylase inhibitory activity of diosmetin and galangin using in silico docking studies.Methods: In this perspective, diosmetin and galangin were prepared for the docking evaluation. Acarbose, a known α-amylase inhibitor was used as the standard. In silico docking studies were carried out using recent version of AutoDock 4.2, which has the basic principle of Lamarckian genetic algorithm.Results: The results showed that the selected flavonoids showed binding energy ranging between -6.84 kcal/mol to  -5.96 kcal/mol when compared with that of the standard (-1.97 kcal/mol. Inhibition constant (9.73 µM to 42.76 µM and intermolecular energy (-8.33 kcal/mol to -7.15 kcal/mol of the ligands also coincide with the binding energy.Conclusion: Diosmetin and galangin contributed excellent α-amylase inhibitory activity than the standard because of its structural parameters. These molecular docking analyses of the selected compounds could lead to the further development to find the potent α-amylase inhibitors for the treatment of diabetes.  

  9. Disulfide bonds of acetylcholinesterase

    The positions of the inter- and intrasubunit disulfide bridges were established for the 11S form of acetylcholinesterase (AChE) isolated from Torpedo californica. A major form of AChE localized within the basal lamina of the synapse is a dimensionally asymmetric molecule which contains either two (13S) or three (17S) sets of catalytic subunits linked to collagenous and non-collagenous structural subunits. Limited proteolysis yields a tetramer of catalytic subunits which sediments at 11S. Each catalytic subunit contains 8 cysteine residues. Initially, these Cys residues were identified following trypsin digestion of the reduced protein alkylated with [14C]-iodoacetate. Peptides were resolved by gel filtration followed by reverse phase HPLC. To determine the disulfide bonding profile, native non-reduced 11S AChE was treated with a fluorescent, sulfhydryl-specific reagent, monobromobimane, prior to proteolytic digestion. One fluorescent Cys peptide was identified indicating that a single sulfhydryl residue was present in its reduced form. Three pairs of disulfide bonded peptides were identified, sequenced, and localized in the polypeptide chain. The Cys residue that is located in the C-terminal tryptic peptide was disulfide bonded to an identical peptide and thus forms the intersubunit crosslink. Finally, the cysteine positions have been compared with the sequence of the homologous protein, thyroglobulin. Both likely share a common pattern of folding

  10. Effect of methyl parathion on the muscle and brain acetylcholinesterase activity of matrinxã (Brycon cephalus

    Almeida Luciana Cristina de

    2005-01-01

    Full Text Available Farming of the freshwater fish is emerging in Brazil and many species from the wild are promising. The teleost matrinxã (Brycon cephalus holds several characteristics such as fast growth rate, high commercial value and adaptability to artificial raring conditions, which make it a promising species for commerce. The use of pesticides in aquatic environment is frequent in Brazil, and methyl parathion is very common in aquaculture. We have determined the enzymatic activity of acetyl cholinesterase in white muscle and brain of matrinxã exposed to 2ppm of environmental methyl parathion for 24 hours. There was 64% and 69% of acetyl cholinesterase inhibition in muscle and brain respectively. These activities were not recovered after 8 days from exposure to this pesticide. It can be concluded that acetyl cholinesterase from those tissues was inhibited by small amounts of methyl parathion, and the main effect was observed in the brain.

  11. Fluorescence properties and sequestration of peripheral anionic site specific ligands in bile acid hosts: Effect on acetylcholinesterase inhibition activity.

    Islam, Mullah Muhaiminul; Aguan, Kripamoy; Mitra, Sivaprasad

    2016-05-01

    The increase in fluorescence intensity of model acetyl cholinesterase (AChE) inhibitors like propidium iodide (PI) and ethidium bromide (EB) is due to sequestration of the probes in primary micellar aggregates of bile acid (BA) host medium with moderate binding affinity of ca. 10(2)-10(3)M(-1). Multiple regression analysis of solvent dependent fluorescence behavior of PI indicates the decrease in total nonradiative decay rate due to partial shielding of the probe from hydrogen bond donation ability of the aqueous medium in bile acid bound fraction. Both PI and EB affects AChE activity through mixed inhibition and consistent with one site binding model; however, PI (IC50=20±1μM) shows greater inhibition in comparison with EB (IC50=40±3μM) possibly due to stronger interaction with enzyme active site. The potency of AChE inhibition for both the compounds is drastically reduced in the presence of bile acid due to the formation of BA-inhibitor complex and subsequent reduction of active inhibitor fraction in the medium. Although the inhibition mechanism still remains the same, the course of catalytic reaction critically depends on equilibrium binding among several species present in the solution; particularly at low inhibitor concentration. All the kinetic parameters for enzyme inhibition reaction are nicely correlated with the association constant for BA-inhibitor complex formation. PMID:26974580

  12. Inhibitory effect of mTOR activator MHY1485 on autophagy: suppression of lysosomal fusion.

    Yeon Ja Choi

    Full Text Available Autophagy is a major degradative process responsible for the disposal of cytoplasmic proteins and dysfunctional organelles via the lysosomal pathway. During the autophagic process, cells form double-membraned vesicles called autophagosomes that sequester disposable materials in the cytoplasm and finally fuse with lysosomes. In the present study, we investigated the inhibition of autophagy by a synthesized compound, MHY1485, in a culture system by using Ac2F rat hepatocytes. Autophagic flux was measured to evaluate the autophagic activity. Autophagosomes were visualized in Ac2F cells transfected with AdGFP-LC3 by live-cell confocal microscopy. In addition, activity of mTOR, a major regulatory protein of autophagy, was assessed by western blot and docking simulation using AutoDock 4.2. In the result, treatment with MHY1485 suppressed the basal autophagic flux, and this inhibitory effect was clearly confirmed in cells under starvation, a strong physiological inducer of autophagy. The levels of p62 and beclin-1 did not show significant change after treatment with MHY1485. Decreased co-localization of autophagosomes and lysosomes in confocal microscopic images revealed the inhibitory effect of MHY1485 on lysosomal fusion during starvation-induced autophagy. These effects of MHY1485 led to the accumulation of LC3II and enlargement of the autophagosomes in a dose- and time-dependent manner. Furthermore, MHY1485 induced mTOR activation and correspondingly showed a higher docking score than PP242, a well-known ATP-competitive mTOR inhibitor, in docking simulation. In conclusion, MHY1485 has an inhibitory effect on the autophagic process by inhibition of fusion between autophagosomes and lysosomes leading to the accumulation of LC3II protein and enlarged autophagosomes. MHY1485 also induces mTOR activity, providing a possibility for another regulatory mechanism of autophagy by the MHY compound. The significance of this study is the finding of a novel

  13. Sesquiterpenoids and Diterpenoids from the Wood of Cunninghamia konishii and Their Inhibitory Activities against NO Production

    Chi-I Chang

    2016-04-01

    Full Text Available Three new sesquiterpenoids, 2α-hydroxy-3,3,6α,9β-tetramethyltricyclo[4,3,21,4]undecane (1, 11-acetoxyeudesman-4β-ol (4, and 2α,3β-dihydroxy-4β-methyl-6,8,10-cadinatriene (6, four known sesquiterpenoids (2, 3, 5, and 7, together with eight known diterpenoids (8–15, were isolated from the wood of Cunninghamia konishii. Their structures were determined by detailed analysis of spectroscopic data and comparison with the data of known analogues. Four sesquiterpenoids (1, 4, 5, and 6 and all the diterpenoids (8–15 were evaluated for inhibition of nitric oxide production in lipopolysaccharides (LPS-activated RAW 264.7 macrophages and the results showed that compounds 10 and 15 exhibited moderate inhibitory activities against nitric oxide production.

  14. Myeloperoxidase inhibitory and radical scavenging activities of flavones from Pterogyne nitens.

    Fernandes, Daniara Cristina; Regasini, Luis Octávio; Vellosa, José Carlos Rebuglio; Pauletti, Patrícia Mendonça; Castro-Gamboa, Ian; Bolzani, Vanderlan Silva; Oliveira, Olga Maria Mascarenhas; Silva, Dulce Helena Siqueira

    2008-05-01

    Two new flavone glucosides, nitensosides A and B (1, 2), together with four known compounds, sorbifolin (3), sorbifolin 6-O-beta-glucopyranoside (4), pedalitin (5), and pedalitin 6-O-beta-glucopyranoside (6) were isolated from Pterogyne nitens. Their structures were elucidated from 1D and 2D NMR analysis, as well as by high resolution mass spectrometry. All the isolated flavones were evaluated for their myeloperoxidase (MPO) inhibitory activity. The most active compound, pedalitin, exhibited IC50 value of 3.75 nM on MPO. Additionally, the radical-scavenging capacity of flavones 1-6 was evaluated towards ABTS and DPPH radicals and compared to standard compounds quercetin and Trolox. PMID:18451567

  15. Inhibitory Activities of Cudrania tricuspidata Leaves on Pancreatic Lipase In Vitro and Lipolysis In Vivo

    Young Sook Kim

    2012-01-01

    Full Text Available To identify effective herb to treat obesity, we screened 115 herbal extracts for inhibition of porcine pancreatic lipase (triacylg-ycerol acylhydrolase, EC 3.1.1.3 activity in vitro. Of the extracts tested, Cudrania tricuspidata leaves exhibited the most pronounced inhibitory effect on lipase activity with an IC50 value of 9.91 μg/mL. Antilipid absorption effects of C. tricuspidata leaves were examined in rats after oral administration of lipid emulsions containing 50 or 250 mg  C. tricuspidata/kg body weight. Plasma triacylglycerol levels 2 h after the oral administration of emulsions containing C. tricuspidata were significantly reduced compared to the untreated group (P<0.05. These results suggest that C. tricuspidata leaves may be useful for the treatment of obesity.

  16. Inhibitory activity of root canal irrigants against Candida albicans, Enterococcus faecalis and Staphylococcus aureus

    Tatiana Kelly da Silva Fidalgo

    2010-12-01

    Full Text Available The present study evaluated the antimicrobial activity of three root canal irrigants against Enterococcus faecalis, Candida albicans, and Staphylococcus aureus. These microorganisms were incubated in the presence of citric acid (6 and 10%, EDTA (17%, and NaOCl (0.5, 1.0, 2.5, and 5.25%. Agar diffusion tests were performed and redox indicator resazurin was used to evaluate the inhibitory effect of the irrigants on the metabolic activity of these microorganisms. The mean diameters of the inhibition zones for the C. albicans cultures were 11.6 mm (17% EDTA, 5.5 mm (0.5% NaOCl, 12.9 mm (1% NaOCl, 22.1 mm (2.5% NaOCl, and 28.5 mm (5.25% NaOCl. The mean diameters of the inhibition zones for E. faecalis were 2.8 mm (1% NaOCl, 5.4 mm (2.5% NaOCl, and 8.3 mm (5.25% NaOCl. For S. aureus, the mean values were 8.0 mm (17% EDTA, 3.0 mm (1% NaOCl, 8.8 mm (2.5% NaOCl, and 10.0 mm (5.25% NaOCl. Most of the irrigant solutions presented effective antimicrobial activity against C. albicans. A high inhibitory effect on the metabolic activity of E. faecalis was detected when the microorganisms were incubated with 17% EDTA. The same result was reached when S. aureus was incubated in the presence of > 2.5% NaOCl. Altogether, these results indicate that 2.5% and 5.25% NaOCl are microbicides against S. aureus while 0.5% and 1% NaOCl are only microbiostatic against the tested bacteria. The 6% and 10% citric acid as well as 17% EDTA did not affect the viability of any of the assayed microorganisms.

  17. IN VITRO SOLUBLE EPOXIDE HYDROLASE ENZYME INHIBITORY ACTIVITY OF SOME NOVEL CHALCONE DERIVATIVES

    Kuppusamy Asokkumar

    2012-09-01

    Full Text Available Objective Soluble epoxide hydrolase (sEH belongs to the α/β -hydrolase superfamily, a subclass of α/β proteins. Chalcones are chemical compounds that show hopeful obliging efficacy in controlling numerous diseases. The main objective of the study is to evaluate the sEH inhibitory activity of some synthesized chalcone derivatives and identification of its mode of inhibition. Methods Four different chalcone derivatives (PC-1 to PC-4 were selected for synthesis by Claisen-Schmidt method. The in vitro sEH inhibitory activity was performed for the synthesized compounds by fluorimetric assay. The percentage of sEH activity and IC50 values were calculated for the synthesized compounds. Dissociation constant were determined by following the method described by Lineweaver-Burks plot.Results and Conclusions The IC50 value obtained for PC-1, PC-2, PC-3, and PC-4 were found to be 0.8213 µg/mL, 2.64 µg/mL, 0.2490 µg/mL and 0.5238 µg/mL respectively. The order of potency (IC50 of the chalcone and chalcone oxide in sEH inhibition assay was PC-3 > PC-4 > PC-1 >PC-2. All the compounds (PC-1, PC-2, PC-3 showed mixed type of inhibition except PC-4 which showed non-competitive type of inhibition. Further in vivo studies are to be carried out for these compounds to confirm their activity and explore the mechanism by which these compounds act and rationalize their use.

  18. Flavonoids from Litchi(Litchi chinensis Sonn.) Seeds and Their Inhibitory Activities on α-Glucosidase

    REN Shen; XU Duo-duo; GAO Yang; MA Yu-ting; GAO Qi-pin

    2013-01-01

    With the bioactivity-guided method,a new flavanone glycoside,together with nine known flavonoids were isolated from 50% aqueous ethanol of litchi(Litchi chinensis Sonn.) seeds.The chemical structure of the new compound was elucidated via 1D and 2D nuclear magnetic resonance(NMR) techniques and mass spectrometry to be (2S)-pinocembrin-7-O-(6"-O-α-L-arabinosyl-β-D-glucopyranoside)(1),and the nine known compounds were determined to be quercetin(2),phlorhizin(3),pinocembrin-7-O-glucoside(4),kaempferol-7-O-β-D-glucopyranoside(5),onychin(6),nairutin(7),narcissin(8),pinocembrin-7-O-[(6"-O-β-D-glucopyranoside)-β-D-glucopyranoside](9) and pinocembrin-7-O-[(2",6"-di-O-α-L-rhamnopyranosyl)-β-D-glucopyranoside](10).Some of the isolated flavonoids were tested for their inhibitory effects on α-glucosidase.And compounds 2 and 3 showed stronger inhibitory activity than positive control.

  19. Production of feline leukemia inhibitory factor with biological activity in Escherichia coli.

    Kanegi, R; Hatoya, S; Tsujimoto, Y; Takenaka, S; Nishimura, T; Wijewardana, V; Sugiura, K; Takahashi, M; Kawate, N; Tamada, H; Inaba, T

    2016-07-15

    Leukemia inhibitory factor (LIF) is a cytokine which is essential for oocyte and embryo development, embryonic stem cell, and induced pluripotent stem cell maintenance. Leukemia inhibitory factor improves the maturation of oocytes in the human and the mouse. However, feline LIF (fLIF) cloning and effects on oocytes during IVM have not been reported. Thus, we cloned complete cDNA of fLIF and examined its biological activity and effects on oocytes during IVM in the domestic cat. The aminoacid sequence of fLIF revealed a homology of 81% or 92% with that of mouse or human. The fLIF produced by pCold TF DNA in Escherichia coli was readily soluble and after purification showed bioactivity in maintaining the undifferentiated state of mouse embryonic stem cells and enhancing the proliferation of human erythrocyte leukemia cells. Furthermore, 10- and 100-ng/mL fLIF induced cumulus expansion with or without FSH and EGF (P Feline LIF will further improve reproduction and stem cell research in the feline family. PMID:27020881

  20. Aldose Reductase Inhibitory Activity of Compounds from  Zea mays L.

    Tae Hyeon Kim

    2013-01-01

    Full Text Available Aldose reductase (AR inhibitors have a considerable therapeutic potential against diabetes complications and do not increase the risk of hypoglycemia. Through bioassay-guided fractionation of an EtOH extract of the kernel from purple corn (Zea mays L., 7 nonanthocyanin phenolic compounds (compound 1–7 and 5 anthocyanins (compound 8–12 were isolated. These compounds were investigated by rat lens aldose reductase (RLAR inhibitory assays. Kinetic analyses of recombinant human aldose reductase (rhAR were performed, and intracellular galactitol levels were measured. Hirsutrin, one of 12 isolated compounds, showed the most potent RLAR inhibitory activity (IC50, 4.78 μM. In the kinetic analyses using Lineweaver-Burk plots of 1/velocity and 1/substrate concentration, hirsutrin showed competitive inhibition against rhAR. Furthermore, hirsutrin inhibited galactitol formation in rat lens and erythrocytes sample incubated with a high concentration of galactose; this finding indicates that hirsutrin may effectively prevent osmotic stress in hyperglycemia. Therefore, hirsutrin derived from Zea mays L. may be a potential therapeutic agent against diabetes complications.

  1. Novel assay utilizing fluorochrome-tagged physostigmine (Ph-F) to in situ detect active acetylcholinesterase (AChE) induced during apoptosis.

    Huang, Xuan; Lee, Brian; Johnson, Gary; Naleway, John; Guzikowski, Anthony; Dai, Wei; Darzynkiewicz, Zbigniew

    2005-01-01

    It was recently reported that acetylcholinesterase (AChE) is expressed in cells undergoing apoptosis and that its presence is essential for assembly of the apoptosome and subsequent caspase-9 activation. To obtain a marker of active AChE that could assay this enzyme in live intact cells and be applicable to fluorescence microscopy and cytometry, the fluorescein-tagged physostigmine (Ph-F), high affinity ligand (inhibitor) reactive with the active center of AChE, was constructed and tested for its ability to in situ label AChE and measure its induction during apoptosis. Ph-F inhibited cholinesterase activity in vitro (IC50 = 10(-6) and 5 x 10(-6) M for equine butyrylcholinesterase and human erythrocyte AChE, respectively) and was a selective marker of cells and structures that were AChE-positive. Thus, exposure of mouse bone marrow cells to Ph-F resulted in the exclusive labeling of megakaryocytes, and of the diaphragm muscle, preferential labeling of the nerve-muscle junctions (end-plates). During apoptosis of carcinoma HeLa cells and leukemic HL-60 or Jurkat cells triggered either by the DNA topoisomerase 1 inhibitor topotecan (TPT) or by oxidative stress (H2O2), the cells become reactive with Ph-F. Their Ph-F derived fluorescence was measured by flow and laser scanning cytometry. The appearance of Ph-F binding sites during apoptosis was preceded by the loss of mitochondrial potential, was concurrent with the presence of activated caspases, and was followed by loss of membrane integrity. At a very early stage of apoptosis, when nucleolar segregation was apparent, the Ph-F binding sites were distinctly localized within the nucleolus and at later stages of apoptosis in the cytoplasm. During apoptosis triggered by TPT, Ph-F binding was preferentially induced in S-phase cells. Our data on megakaryocytes and end-plates indicate that Ph-F reacts with active sites of AChE, and can be used to reveal the presence of this enzyme in live cells and possibly to study its

  2. Associations of Physical Activity, Sports Participation and Active Commuting on Mathematic Performance and Inhibitory Control in Adolescents.

    Sidsel L Domazet

    Full Text Available To examine objectively measured physical activity level, organized sports participation and active commuting to school in relation to mathematic performance and inhibitory control in adolescents.The design was cross-sectional. A convenient sample of 869 sixth and seventh grade students (12-14 years was invited to participate in the study. A total of 568 students fulfilled the inclusion criteria and comprised the final sample for this study. Mathematic performance was assessed by a customized test and inhibitory control was assessed by a modified Eriksen flanker task. Physical activity was assessed with GT3X and GT3X+ accelerometers presented in sex-specific quartiles of mean counts per minute and mean minutes per day in moderate-to-vigorous physical activity. Active commuting and sports participation was self-reported. Mixed model regression was applied. Total physical activity level was stratified by bicycling status in order to bypass measurement error subject to the accelerometer.Non-cyclists in the 2nd quartile of counts per minute displayed a higher mathematic score, so did cyclists in the 2nd and 3rd quartile of moderate-to-vigorous physical activity relative to the least active quartile. Non-cyclists in the 3rd quartile of counts per minute had an improved reaction time and cyclists in the 2nd quartile of counts per minute and moderate-to-vigorous physical activity displayed an improved accuracy, whereas non-cyclists in the 2nd quartile of counts per minute showed an inferior accuracy relative to the least active quartile. Bicycling to school and organized sports participation were positively associated with mathematic performance.Sports participation and bicycling were positively associated with mathematic performance. Results regarding objectively measured physical activity were mixed. Although, no linear nor dose-response relationship was observed there was no indication of a higher activity level impairing the scholastic or cognitive

  3. Macrophage migration inhibitory factor activates hypoxia-inducible factor in a p53-dependent manner.

    Seiko Oda

    Full Text Available BACKGROUND: Macrophage migration inhibitory factor (MIF is not only a cytokine which has a critical role in several inflammatory conditions but also has endocrine and enzymatic functions. MIF is identified as an intracellular signaling molecule and is implicated in the process of tumor progression, and also strongly enhances neovascularization. Overexpression of MIF has been observed in tumors from various organs. MIF is one of the genes induced by hypoxia in an hypoxia-inducible factor 1 (HIF-1-dependent manner. METHODS/PRINCIPAL FINDINGS: The effect of MIF on HIF-1 activity was investigated in human breast cancer MCF-7 and MDA-MB-231 cells, and osteosarcoma Saos-2 cells. We demonstrate that intracellular overexpression or extracellular administration of MIF enhances activation of HIF-1 under hypoxic conditions in MCF-7 cells. Mutagenesis analysis of MIF and knockdown of 53 demonstrates that the activation is not dependent on redox activity of MIF but on wild-type p53. We also indicate that the MIF receptor CD74 is involved in HIF-1 activation by MIF at least when MIF is administrated extracellularly. CONCLUSION/SIGNIFICANCE: MIF regulates HIF-1 activity in a p53-dependent manner. In addition to MIF's potent effects on the immune system, MIF is linked to fundamental processes conferring cell proliferation, cell survival, angiogenesis, and tumor invasiveness. This functional interdependence between MIF and HIF-1alpha protein stabilization and transactivation activity provide a molecular mechanism for promotion of tumorigenesis by MIF.

  4. Comparison of Antioxidant Potential and Rat intestinal a-Glucosidases inhibitory Activities of Quercetin, Rutin, and Isoquercetin

    S-H Jo

    2009-12-01

    Full Text Available Summary: Inhibition of α-amylase and α-glucosidases involved in the digestion and absorption of carbohydrates can decrease the postprandial increase  of blood glucose level after a mixed carbohydrate diet. Therefore, the inhibitory activity of quercetin and its glycoside derivatives such as rutin and isoquercetin against rat intestinal α-glucosidases (sucrase, maltase, glucoamylase, and isomaltase and porcine pancreatic α-amylase were compared in vitro. Among the tested three flavonols, quercetin had the highest maltase, glucoamylase, and isomaltase inhibitory activities. The isomaltase and α-amylase inhibitory activities of the above three flavonols were also compared to a known type 2 diabetes drug (Acarbose, strong  α-amylase inhibitor. Compared  to acarbose, quercetin and its derivatives showed a significant inhibition of isomaltase but did not show high inhibitory activity against porcine pancreatic  α-amylase. Furthermore, the oxygen radical absorbance capacity (ORAC of these flavonols was evaluated. Quercetin had the highest peroxyl radical absorbing activity, followed by rutin and isoquercetin. These results suggest that the selected flavonols which have high ORAC value with α-glucosidase inhibitory activity and low α-amylase activity could be physiologically useful for treatment of diabetes, although in vivo experiments are needed. Industrial relevance: The α-glucosidase inhibitory activity and antioxidant activity in quercetin would be helpful to manage glucose uptake and the glucose-induced increased levels of mitochondrial reactive oxygen species (ROS linked to hyperglycemia. This in vitro study therefore provides the biochemical rationale for the benefit of quercetin-based dietary supplement and enzymatic conversion from rutin or isoquercetin to quercetin for enhancing bioactive food components using high rutin-contained grain such as buckwheat.  

  5. Mushroom tyrosinase inhibitory activity and major fatty acid constituents of Amazonian native flora oils

    Raquel da Silva Teixeira

    2012-09-01

    Full Text Available In order to treat hyperpigmentation-related problems, there has been a global trend in developing cosmetics claiming to have skin-whitening properties, which act by inhibiting melanin biosynthesis. The objective of this work was to evaluate the in vitro mushroom tyrosinase inhibitory activity of five Amazonian native flora oils, and so to verify the possibility of their incorporation into cosmetic products. In addition, the fatty acid composition of the essential oils was determined by gas chromatography-flame ionisation detection in order to determine the main components of these oils. The tyrosinase inhibitory activity of the tested oils was found to be in the following order: açaí (IA50 = 66.08 µg mL-1 > tucumã > patauá > pracaxi > castanha do Brasil. This study suggests that açaí oil has great potential in the treatment of hyperpigmentation and other related disorders, due to its considerable tyrosinase inhibitory activity.Com o intuito de se tratar problemas dermatológicos de hiperpigmentação, há uma tendência mundial no desenvolvimento de cosméticos que possuam propriedades despigmentantes, os quais agem inibindo a biossíntese de melanina. O objetivo deste trabalho foi avaliar in vitro a atividade de inibição da tirosinase de cogumelo de cinco óleos de plantas nativas da Amazônia e, desta forma, verificar a possibilidade de sua incorporação em produtos cosméticos. Ainda, a composição de ácidos graxos dos óleos foi determinada por cromatografia gasosa com detecção por ionização de chama, no intuito de determinar os principais componentes destes óleos. A atividade de inibição da tirosinase dos óleos testados foi encontrada na seguinte ordem: açaí (IA50 = 66,08 µg mL-1 > tucumã > patauá > pracaxi > castanha do Brasil. Este estudo sugere que o óleo de açaí possui grande potencial para o tratamento da hiperpigmentação cutânea e doenças correlatas, devido à sua considerável atividade de inibi

  6. The monoamine oxidase inhibitory activity of essential oils obtained from Eryngium species and their chemical composition.

    Klein-Júnior, Luiz Carlos; Dos Santos Passos, Carolina; Tasso de Souza, Tiago Juliano; Gobbi de Bitencourt, Fernanda; Salton, Juliana; de Loreto Bordignon, Sérgio Augusto; Henriques, Amélia Teresinha

    2016-06-01

    Context Monoamine oxidase (MAO) inhibitors are used in the treatment of depression, anxiety disorders, and the symptomatic treatment of Parkinson's disease. Eryngium, the most representative of the Apiaceae family, is well known for the presence of essential oils (EOs), which have already demonstrated MAO inhibitory potential. Objective The objective of this study is to evaluate the MAO inhibitory capacity of the EOs obtained from Eryngium floribundum Cham. & Schlecht. (EF), E. eriophorum Cham. & Schlecht. (EE), E. nudicaule Lam. (EN), E. horridum Malme (EH), and E. pandanifolium Cham. & Schlecht. (EP). Materials and methods EOs were obtained from fresh whole plants by hydrodistillation (3 h). Chemical analyses were performed by GC/MS using apolar and polar columns, with oven temperature from 60 to 300 °C at 3 °C/min. The MAO-A and -B activities were evaluated in vitro by an end-point method using kynuramine as the substrate and mitochondrial suspension or human recombinant enzymes as the enzymatic source. DMSO 2%, clorgyline 10(-7) M, and pargyline 10(-6) M were used as controls. Results and discussion EFEO, EEEO, ENEO, EHEO, and EPEO GC/MS analysis showed (E)-caryophyllene (4.9-10.8%), germacrene D (0.6-35.1%), bicyclogermacrene (10.4-17.2), spathulenol (0.4-36.0%), and globulol (1.4-18.6%) as main constituents. None of the EOs inhibited MAO-A activity (4 and 40 μg/mL). However, EHEO inhibited MAO-B activity with an IC50 value of 5.65 μg/mL (1-200 μg/mL). Pentadecane (10 μM), its major constituent (53.5%), did not display significant MAO-B inhibition. Conclusion The study demonstrates the promising application of Eryngium species as a source of potential central nervous system bioactive secondary metabolites, specially related to neurodegenerative disorders. PMID:26810928

  7. Sodium salicylate suppresses GABAergic inhibitory activity in neurons of rodent dorsal raphe nucleus.

    Yan Jin

    Full Text Available Sodium salicylate (NaSal, a tinnitus inducing agent, can activate serotonergic (5-HTergic neurons in the dorsal raphe nucleus (DRN and can increase serotonin (5-HT level in the inferior colliculus and the auditory cortex in rodents. To explore the underlying neural mechanisms, we first examined effects of NaSal on neuronal intrinsic properties and the inhibitory synaptic transmissions in DRN slices of rats by using whole-cell patch-clamp technique. We found that NaSal hyperpolarized the resting membrane potential, decreased the input resistance, and suppressed spontaneous and current-evoked firing in GABAergic neurons, but not in 5-HTergic neurons. In addition, NaSal reduced GABAergic spontaneous and miniature inhibitory postsynaptic currents in 5-HTergic neurons. We next examined whether the observed depression of GABAergic activity would cause an increase in the excitability of 5-HTergic neurons using optogenetic technique in DRN slices of the transgenic mouse with channelrhodopsin-2 expressed in GABAergic neurons. When the GABAergic inhibition was enhanced by optical stimulation to GABAergic neurons in mouse DRN, NaSal significantly depolarized the resting membrane potential, increased the input resistance and increased current-evoked firing of 5-HTergic neurons. However, NaSal would fail to increase the excitability of 5-HTergic neurons when the GABAergic synaptic transmission was blocked by picrotoxin, a GABA receptor antagonist. Our results indicate that NaSal suppresses the GABAergic activities to raise the excitability of local 5-HTergic neural circuits in the DRN, which may contribute to the elevated 5-HT level by NaSal in the brain.

  8. Activation of the chicken gonadotropin-inhibitory hormone receptor reduces gonadotropin releasing hormone receptor signaling.

    Shimizu, Mamiko; Bédécarrats, Grégoy Y

    2010-06-01

    Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic peptide from the RFamide peptide family that has been identified in multiple avian species. Although GnIH has clearly been shown to reduce LH release from the anterior pituitary gland, its mechanism of action remains to be determined. The overall objectives of this study were (1) to characterize the GnIH receptor (GnIH-R) signaling pathway, (2) to evaluate potential interactions with gonadotropin releasing hormone type III receptor (GnRH-R-III) signaling, and (3) to determine the molecular mechanisms by which GnIH and GnRH regulate pituitary gonadotrope function during a reproductive cycle in the chicken. Using real-time PCR, we showed that in the chicken pituitary gland, GnIH-R mRNA levels fluctuate in an opposite manner to GnRH-R-III, with higher and lower levels observed during inactive and active reproductive stages, respectively. We demonstrated that the chicken GnIH-R signals by inhibiting adenylyl cyclase cAMP production, most likely by coupling to G(alphai). We also showed that this inhibition is sufficient to significantly reduce GnRH-induced cAMP responsive element (CRE) activation in a dose-dependent manner, and that the ratio of GnRH/GnIH receptors is a significant factor. We propose that in avian species, sexual maturation is characterized by a change in GnIH/GnRH receptor ratio, resulting in a switch in pituitary sensitivity from inhibitory (involving GnIH) to stimulatory (involving GnRH). In turn, decreasing GnIH-R signaling, combined with increasing GnRH-R-III signaling, results in significant increases in CRE activation, possibly initiating gonadotropin synthesis. PMID:20350548

  9. Virtual Screening Analysis and In-vitro Xanthine Oxidase Inhibitory Activity of Some Commercially Available Flavonoids.

    Umamaheswari, Muthuswamy; Madeswaran, Arumugam; Asokkumar, Kuppusamy

    2013-01-01

    Allopurinol, the xanthine oxidase inhibitor, is the only drug available for the treatment of gout. We examined the xanthine oxidase inhibitory activity of some commercially available flavonoids such asepigallocatechin, acacatechin, myricetin, naringenin, daidzein and glycitein by virtual screening and in-vitro studies. The interacting residues within the complex model and their contact types were identified. The virtual screening analysis were carried out using AutoDock 4.2 and in-vitro xanthine oxidase inhibitory activity was carried out using xanthine as the substrate. In addition, enzyme kinetics was performed using LineweaverBurkplot analysis. Allopurinol, a known xanthine oxidase inhibitor was used as the standard. The docking energy ofglycitein was found to be -8.49 kcal/mol which was less than that of the standard (-4.47 kcal/ mol). All the selected flavonoids were found to exhibit lower binding energy (-8.08 to -6.03 kcal/ mol) than allopurinol. The docking results confirm that flavonoids showed greater inhibition of xanthine oxidase due to their active binding sites and lesser binding energies compared to allopurinol. This may be attributed to the presence of benzopyran ring in the flavonoids. In the xanthine oxidase assay, IC50 value of glycitein was found to be 12±0.86 μg/mL, whereas that of allopurinol was 24±0.28 μg/mL. All the remaining compounds exhibited IC50 values ranging between 22±0.64 to 62±1.18 μg/mL. In the enzyme kinetic studies, flavonoids showed competitive type of enzyme inhibition. It can be concluded that flavonoids could be a promising remedy for the treatment of gout and related inflammatory disorders. Further in-vivo studies are required to develop potential compounds with lesser side effects. PMID:24250638

  10. Exosomes released from Mycoplasma infected tumor cells activate inhibitory B cells.

    Chenjie Yang

    Full Text Available Mycoplasmas cause numerous human diseases and are common opportunistic pathogens in cancer patients and immunocompromised individuals. Mycoplasma infection elicits various host immune responses. Here we demonstrate that mycoplasma-infected tumor cells release exosomes (myco+ exosomes that specifically activate splenic B cells and induce splenocytes cytokine production. Induction of cytokines, including the proinflammatory IFN-γ and the anti-inflammatory IL-10, was largely dependent on the presence of B cells. B cells were the major IL-10 producers. In splenocytes from B cell deficient μMT mice, induction of IFN-γ+ T cells by myco+ exosomes was greatly increased compared with wild type splenocytes. In addition, anti-CD3-stimulated T cell proliferation was greatly inhibited in the presence of myco+ exosome-treated B cells. Also, anti-CD3-stimulated T cell signaling was impaired by myco+ exosome treatment. Proteomic analysis identified mycoplasma proteins in exosomes that potentially contribute to the effects. Our results demonstrate that mycoplasma-infected tumor cells release exosomes carrying mycoplasma components that preferentially activate B cells, which in turn, are able to inhibit T cell activity. These results suggest that mycoplasmas infecting tumor cells can exploit the exosome pathway to disseminate their own components and modulate the activity of immune cells, in particular, activate B cells with inhibitory activity.

  11. Isopimarane diterpenoids from Kaempferia pulchra rhizomes collected in Myanmar and their Vpr inhibitory activity.

    Win, Nwet Nwet; Ito, Takuya; Matsui, Takashi; Aimaiti, Simayijiang; Kodama, Takeshi; Ngwe, Hla; Okamoto, Yasuko; Tanaka, Masami; Asakawa, Yoshinori; Abe, Ikuro; Morita, Hiroyuki

    2016-04-01

    Viral protein R (Vpr), an accessory gene of HIV-1, plays important roles in viral pathogenesis. Screening of Myanmar medicinal plants that are popular as primary treatments for HIV/AIDS and for HIV-related problems revealed the potent anti-Vpr activity of the CHCl3-soluble extract of Kaempferia pulchra rhizomes, in comparison with that of the positive control, damnacanthal. Fractionation of the active CHCl3-soluble extract led to the identification of 30 isopimarane diterpenoids, including kaempulchraols A-W (1-23). All isolates were assayed for anti-Vpr activity against TREx-HeLa-Vpr cells, in which Vpr expression is tightly regulated by tetracycline. Kaempulchraols B (2), D (4), G (7), Q (17), T (20), U (21), and W (23) exhibited potent anti-Vpr activity, at concentrations ranging from 1.56 to 6.25μM. The structure-activity relationships of the active kaempulchraols suggested that the presence of a hydroxy group at C-14 in an isopimara-8(9),15-diene skeleton and the presence of an acetoxy group at C-1 or C-7 in an isopimara-8(14),15-diene skeleton are the critical factors for the inhibitory effects against TREx-HeLa-Vpr cells. PMID:26916438

  12. Inducible expression pattern of rice Bowman-Birk inhibitor gene Os WIP1-2 and its protease inhibitory activity

    CHEN Jun; LIU Jing; GUO Lei; QU Lijia; CHEN Zhangliang; GU Hongya

    2004-01-01

    The WIP1-2 gene was cloned from rice. It belongs to the Bowman-Birk inhibitor gene family. Northern blot showed that expression of this gene was induced by wounding and jasmonic acid (JA). It indicates that the OsWIP1 gene plays an important role in the rice defense system. The OsWIP1-2 was cloned into pET28a and expressed in E. Coli. Its expressed product was purified in the form of fusion protein and tested for the inhibitory activities against trypsin and chymotrypsin. It was found that the fusion protein could inhibit chymotrypsin, but not trypsin. It was also found that the His tag at its C-terminal affected its inhibitory activity significantly. The fusion protein with a natural C-terminal had the inhibitory activity, while no inhibitory activity was detected in the fusion protein with a (His)6-tag at its C-terminal. This implies that extra amino acid residues at the C-terminal of OsWIP1-2 may interfere with its correct folding. The inhibitory assay indicated that the members of rice Bowman-Birk inhibitor gene family probably differentiated both in their structure and function.

  13. Molecular docking and ex vivo and in vitro anticholinesterase activity studies ofSalvia sp. and highlighted rosmarinic acid

    DEMİREZER, LÜTFİYE ÖMÜR; GÜRBÜZ, PERİHAN; UĞUR, EMİNE PELİN KELİCEN; BODUR, MİNE; ÖZENVER, NADİRE; UZ, AYŞE; GÜVENALP, Zühal

    2015-01-01

    Background/aim: To evaluate acetylcholinesterase (AChE) inhibitory activity and antioxidant capacity of the major molecule from Salvia sp., rosmarinic acid, as a drug candidate molecule for treatment of Alzheimer disease (AD). Materials and methods: The AChE inhibitory activity of different extracts from Salvia trichoclada, Salvia verticillata, and Salvia fruticosa was determined by the Ellman and isolated guinea pig ileum methods, and the antioxidant capacity was determined with DPPH. The A...

  14. Chitinase-mediated inhibitory activity of Brassica transgenic on growth of Alternaria brassicae.

    Mondal, Kalyan K; Chatterjee, Subhas Chandra; Viswakarma, Navin; Bhattacharya, Ram Charan; Grover, Anita

    2003-09-01

    Chitinase, capable of degrading the cell walls of invading phytopathogenic fungi, plays an important role in plant defense response, particularly when this enzyme is overexpressed through genetic engineering. In the present study, Brassica plant (Brassica juncea L.) was transformed with chitinase gene tagged with an overexpressing promoter 35 S CaMV. The putative transgenics were assayed for their inhibitory activity against Alternaria brassicae, the inducer of Alternaria leaf spot of Brassica both in vitro and under polyhouse conditions. In in vitro fungal growth inhibition assays, chitinase inhibited the fungal colony size by 12-56% over the non-trangenic control. The bioassay under artificial epiphytotic conditions revealed the delay in the onset of disease as well as reduced lesion number and size in 35S-chitinase Brassica as compared to the untransformed control plants. PMID:14570264

  15. Terpenoids with alpha-glucosidase inhibitory activity from the submerged culture of Inonotus obliquus.

    Ying, You-Min; Zhang, Lin-Yan; Zhang, Xia; Bai, Hai-Bo; Liang, Dong-E; Ma, Lie-Feng; Shan, Wei-Guang; Zhan, Zha-Jun

    2014-12-01

    Lanostane-type triterpenoids, inotolactones A and B, a drimane-type sesquiterpenoid, inotolactone C, and five known terpenoids 6β-hydroxy-trans-dihydroconfertifolin, inotodiol, 3β,22-dihydroxyanosta-7,9(11),24-triene, 3β-hydroxycinnamolide, and 17-hydroxy-ent-atisan-19-oic acid, were isolated from the submerged culture of chaga mushroom, Inonotus obliquus. Their structures were characterized by spectroscopic methods, including MS and NMR (1D and 2D) spectroscopic techniques. Inotolactones A and B, examples of lanostane-type triterpenoids bearing α,β-dimethyl, α,β-unsaturated δ-lactone side chains, exhibited more potent alpha-glucosidase inhibitory activities than the positive control acarbose. This finding might be related to the anti-hyperglycemic properties of the fungus and to its popular role as a diabetes treatment. In addition, a drimane-type sesquiterpenoid and an atisane-type diterpenoid were isolated from I. obliquus. PMID:25446238

  16. Synthesis and HIV-1 Reverse Transcriptase Inhibitory Activity of Non-Nucleoside Phthalimide Derivatives

    UNGWITAYATORN Jiraporn; WIWAT Chanpen; MATAYATSUK Chutima; PIMTHON Jutarat; PIYAVIRIYAKUL Suratsawadee

    2008-01-01

    A new type of non-nucleoside HIV-1 reverse transcriptase inhibitors in phthalimide series has been synthesized from either the reaction of N-carboethoxyphthalimide with amines or phthalimide with appropriate alkyl halides.The in vitro inhibitory activity of the synthesized compounds was studied by a radiometric assay at a concentration of 200 μg/mL using poly(rA)-oligo(dT) as a template-primer and methyl-[3H]dTTP as a substrate.The three most potent compounds, N-(m,p-dihydroxybenzyl)phthalimide (11), N-[2-(a-furyl)ethyl]phthalimide (29) and N-(5-methylpyrazin-2-ylmethyl)phthalimide (25) exhibited IC50 values of 60.90, 98.10 and 120.75 μg/mL, respecas a substrate).

  17. MAO-A inhibitory activity of quercetin from Calluna vulgaris (L.) Hull

    Saaby, Lasse; Rasmussen, Hasse Bonde; Jäger, Anna Katharina

    2009-01-01

    water. The three fractions were tested in a photometric peroxidase linked MAO-A bioassay. The ethyl acetate phase showed the highest MAO-A inhibitory activity. Quercetin was isolated by VLC through bioassay-guided fractionation and purified by re-crystallisation. The structure was elucidated by LC......-MS and (1)H NMR. RESULTS: The IC(50)-value for MAO-A inhibition by quercetin was 18+/-0.2muM in an assay where the IC(50)-value for MAO-A inhibition by clorgylin was 0.2+/-0.02muM. CONCLUSION: The content of quercetin in Calluna vulgaris might explain the reported nerve calming effect of the plant....

  18. Synthesis, leishmanicidal and enzyme inhibitory activities of quinoline-4-carboxylic acids

    A series of quinoline-4-carboxylic acids 1-13 was synthesized and screened for their leishmanicidal, phosphodiesterase, beta-glucuronidase and urease inhibitory properties. Only compounds 3 and 7 were found to be active against leishmaniasis with IC/sub 50/ values of 76.26 +- 0.71 and 62.86 +- 0.35 macro g/ml, respectively. In phosphodiesterase assay only compound 13 showed maximum percentage inhibition (47.2%) among all the tested compounds. Compound 9 showed maximum percentage inhibition value (47.4%) against p-glucuronidase enzyme. Compound 13 showed maximum percentage inhibition value i.e. 14.10 % against urease enzyme. The structures of all the synthetic compounds were deduced by spectroscopic techniques, including /sup 1/H NMR, EI-MS, IR, and UV spectroscopy. (author)

  19. Prenylcoumarin with Rev-export inhibitory activity from Cnidii Monnieris Fructus.

    Tamura, Satoru; Fujitani, Toshiaki; Kaneko, Masafumi; Murakami, Nobutoshi

    2010-06-15

    By use of the fission yeast expressing the model fusion protein comprised of GST, SV40 T antigen NLS, GFP, and Rev-NES in the bioassay, the prenylcoumarin osthol (1) was disclosed as the new Rev-export inhibitor from the MeOH extract of Cnidii Monnieris Fructus. Furthermore, 1 was also found to inhibit export the genuine Rev in HeLa cells by indirect fluorescent antibody technique. By the competitive experiment using the biotinylated probe 3, osthol (1) was revealed to inhibit nuclear export of Rev through a NES non-antagonistic mode. Structure-activity relationship analysis of several analogs of 1 clarified that both prenyl side chain and double bond adjacent to the lactone carbonyl residue play an important role in the Rev-export inhibitory potency of 1. PMID:20493693

  20. Synthesis, protein kinase inhibitory potencies, and in vitro antiproliferative activities of meridianin derivatives.

    Giraud, Francis; Alves, Georges; Debiton, Eric; Nauton, Lionel; Théry, Vincent; Durieu, Emilie; Ferandin, Yoan; Lozach, Olivier; Meijer, Laurent; Anizon, Fabrice; Pereira, Elisabeth; Moreau, Pascale

    2011-07-14

    The synthesis of new meridianin derivatives is described. The indolic ring system was substituted at the C-4 to C-7 positions either by a bromine atom or by nitro or amino groups. Additionally, an iodine atom or various aryl groups were introduced at the C-5 position of the 2-aminopyrimidine ring. These compounds as well as some of their synthetic intermediates were tested for their kinase inhibitory potencies and for their in vitro antiproliferative activities. We found that this series of compounds is particularly interesting in the development of new inhibitors of DYRK1A and CLK1 kinases. The most effective compounds toward these two kinase families are the 6- and 7-bromo derivatives 30, 33, and 34 that showed more than 45-fold selectivity toward DYRK1A/CLK1 kinases over the other kinases tested. Meridianin derivatives could thus be developed toward potent and selective inhibitors of key RNA splicing regulators and potential therapeutic agents. PMID:21623630

  1. Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding

    Suyama, Shigetomo; Maekawa, Fumihiko; Maejima, Yuko; Kubota, Naoto; Kadowaki, Takashi; Yada, Toshihiko

    2016-01-01

    Adiponectin regulates glucose and lipid metabolism, acting against metabolic syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts on the brain including hypothalamic arcuate nucleus (ARC), where proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several studies have examined intracerebroventricular (ICV) injection of adiponectin and reported opposite effects, increase or decrease of food intake. These reports used different nutritional states. The present study aimed to clarify whether adiponectin exerts distinct effects on food intake and ARC POMC neurons depending on the glucose concentration. Adiponectin was ICV injected with or without glucose for feeding experiments and administered to ARC slices with high or low glucose for patch clamp experiments. We found that adiponectin at high glucose inhibited POMC neurons and increased food intake while at low glucose it exerted opposite effects. The results demonstrate that glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding. PMID:27503800

  2. Lactobacillus isolates from weaned piglets' mucosa with inhibitory activity against common porcine pathogens.

    Hacin, B; Rogelj, I; Matijasić, B B

    2008-01-01

    Twelve lactobacilli isolates from mucosa of 3-5-week-old weaned pigs were found to exert good antimicrobial activity against common porcine pathogens (S. aureus, B. cereus, E. coli, C. perfringens). Two of them produced in addition to lactic acid also considerable amounts of acetic acid, and 6 of them produced hydrogen peroxide and metabolites other than organic acids. Isolates 4/26 and 2/25 (identified as L. crispatus or L. amylovorus) were inhibitory against most strains of S. aureus, B. cereus and E. coli, and especially the strain 4/26 survived well in simulated gastric and intestinal juice. Diarrhea-causing E. coli O8K88H9 Ent(+) was successfully inhibited by the growing culture as well as by the catalase-treated and neutralized supernatant of L. reuteri 12/26. Mucin degradation and multiple resistance to antibiotics were not observed. PMID:19381487

  3. The effects of inhibitory control training for preschoolers on reasoning ability and neural activity

    Liu, Qian; Zhu, Xinyi; Ziegler, Albert;

    2015-01-01

    in the training group (N = 20; 12 boys, mean age 4.87 ± 0.26 years) played “Fruit Ninja” on a tablet computer for 15 min/day, 4 days/week, for 3 weeks. Children in the active control group (N = 20; 10 boys, mean age 4.88 ± 0.20 years) played a coloring game on a tablet computer for 10 min/day, 1–2 days....../week, for 3 weeks. Several cognitive tasks (involving inhibitory control, working memory, and fluid intelligence) were used to evaluate the transfer effects, and electroencephalography (EEG) was performed during a go/no-go task. Progress on the trained game was significant, while performance on a reasoning...

  4. Antioxidant and α-Glucosidase Inhibitory Activities of Isolated Compounds from Ipomoea aquatica

    Umar Lawal

    2016-05-01

    Full Text Available Ipomoea aquatica Forsk is a green leafy vegetable that is a rich source of amino acids and vitamins. Antioxidant and α-glucosidase inhibitory activities of the hexane (IAHE and methanol (IAME fractions of the vegetable portion of I. aquatica were investigated. The IAME fraction exhibited a strong scavenging effect of the 2,2-diphenyl-2-picryl hydrazyl (DPPH free radicals, and this fraction contained the highest phenolic contents. Phytochemical investigation of the IAME fraction yielded three known compounds, namely 3,5-di-O-caffeoylquinic acid (1, 4,5-di-O-caffeoylquinic acid (2 and quercetin 3-O-β-D-glucoside (3. The structures were unambiguously elucidated based on 1D and 2D-NMR analyses (1H, 13C, COSY, HSQC, HMBC and mass spectrometry data. Compound 3 was isolated for the first time from this plant.

  5. Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding.

    Suyama, Shigetomo; Maekawa, Fumihiko; Maejima, Yuko; Kubota, Naoto; Kadowaki, Takashi; Yada, Toshihiko

    2016-01-01

    Adiponectin regulates glucose and lipid metabolism, acting against metabolic syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts on the brain including hypothalamic arcuate nucleus (ARC), where proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several studies have examined intracerebroventricular (ICV) injection of adiponectin and reported opposite effects, increase or decrease of food intake. These reports used different nutritional states. The present study aimed to clarify whether adiponectin exerts distinct effects on food intake and ARC POMC neurons depending on the glucose concentration. Adiponectin was ICV injected with or without glucose for feeding experiments and administered to ARC slices with high or low glucose for patch clamp experiments. We found that adiponectin at high glucose inhibited POMC neurons and increased food intake while at low glucose it exerted opposite effects. The results demonstrate that glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding. PMID:27503800

  6. Valuing the Endangered Species Antirrhinum lopesianum: Neuroprotective Activities and Strategies for in vitro Plant Propagation

    Andreia Gomes; Sofia Fortalezas; Rui Pimpão; Inês Figueira; João Maroco; Carlos Aguiar; Ricardo B. Ferreira; Célia Miguel; Cláudia N. Santos

    2013-01-01

    Plant phytochemicals are described as possessing considerable neuroprotective properties, due to radical scavenging capacity and acetylcholinesterase inhibitory activity, important bioactivities in neurodegeneration. Antirrhinum lopesianum is a rare endemism from the Iberian Peninsula, occurring at the northeastern border between Portugal and Spain. It is classified as Endangered, due to its highly fragmented geographical occupation, facing a high risk of extinction in the Portuguese territor...

  7. Structural and Kinetic Analyses of Macrophage Migration Inhibitory Factor Active Site Interactions

    Crichlow, G.; Lubetsky, J; Leng, L; Bucala, R; Lolis, E

    2009-01-01

    Macrophage migration inhibitory factor (MIF) is a secreted protein expressed in numerous cell types that counters the antiinflammatory effects of glucocorticoids and has been implicated in sepsis, cancer, and certain autoimmune diseases. Interestingly, the structure of MIF contains a catalytic site resembling the tautomerase/isomerase sites of microbial enzymes. While bona fide physiological substrates remain unknown, model substrates have been identified. Selected compounds that bind in the tautomerase active site also inhibit biological functions of MIF. It had previously been shown that the acetaminophen metabolite, N-acetyl-p-benzoquinone imine (NAPQI), covalently binds to the active site of MIF. In this study, kinetic data indicate that NAPQI inhibits MIF both covalently and noncovalently. The structure of MIF cocrystallized with NAPQI reveals that the NAPQI has undergone a chemical alteration forming an acetaminophen dimer (bi-APAP) and binds noncovalently to MIF at the mouth of the active site. We also find that the commonly used protease inhibitor, phenylmethylsulfonyl fluoride (PMSF), forms a covalent complex with MIF and inhibits the tautomerase activity. Crystallographic analysis reveals the formation of a stable, novel covalent bond for PMSF between the catalytic nitrogen of the N-terminal proline and the sulfur of PMSF with complete, well-defined electron density in all three active sites of the MIF homotrimer. Conclusions are drawn from the structures of these two MIF-inhibitor complexes regarding the design of novel compounds that may provide more potent reversible and irreversible inhibition of MIF.

  8. Determination of a-glucosidase inhibitory activity from selected Fabaceae plants.

    Dej-Adisai, Sukanya; Pitakbut, Thanet

    2015-09-01

    Nineteen plants from Fabaceae family, which were used in Thai traditional medicine for treatment of diabetes, were determined of α-glucosidase inhibitory activity via enzymatic reaction. In this reaction, α-glucosidase was used as enzyme, which, reacted with the substrate, p-nitrophenol-D-glucopyranoside (pNPG). After that the product, p-nitro phenol (pNP) will be occurred and observed the yellow colour at 405 nm. In this study, acarbose was used as positive standard which, inhibited this enzyme with IC₅₀ as 331 ± 4.73 μg/ml. Caesalpinia pulcherrima leaves showed the highest activity with IC₅₀ as 436.97 ± 9.44 μg/ml. Furthermore, Bauhinia malabarica leaves presented moderately activity with IC₅₀ as 745.08 ± 11.15 μg/ml. However, the other plants showed mild to none activity of α-glucosidase inhibition. Accordingly, this study can support anti-diabetes of these plants in traditional medicine and it will be the database of the biological activity of Fabaceae plant. PMID:26408887

  9. INHIBITORY ACTIVITY OF FLAVONOIDS ON THE LENS ALDOSE REDUCTASE OF HEALTHY AND DIABETIC RATS

    M. T. Goodarzi

    2006-05-01

    Full Text Available Aldose reductase is a critical enzyme in the polyol pathway that plays an important role in diabetes mellitus. Inhibition of the activity of this enzyme can prevent cataract in diabetic patients’lenses. In this study the inhibitory effect of two flavonoids, quercetin and naringin, in the activity of aldose reductase in streptozotocin-induced diabetic and healthy rats were investigated. Thirty male rats were divided in six groups. The first, second and third group were healthy rats that received water,quercetin and naringin, respectively. The fourth, fifth and sixth groups were streptozocin-induced diabetic rats that received water, quercetin and naringin, respectively. These rats were fed orally in a definite dose from each substance for 12 days. After this period rats were scarified and their lenses were separated and homogenized. The activity of aldose reductase was measured in each homogenized sample separately. The effect of feeding of these substances in blood sugar was also determined. Aldose reductase activity was reduced 73 and 69 percent in diabetic rats fed by quercetin and naringin, respectively, and the difference compared to control group was significant. In healthy rats this reduction was 63 and 59 percent, respectively, and the difference was significant compared to those who did not receive flavonoids. It was concluded that these substances were effective in reduction of aldose reductase activity in vivo and consequently could delay the progress of cataract.

  10. Elemental Composition, Anticariogenic, Pancreatic Lipase Inhibitory and Cytotoxic Activity of Artocarpus Lakoocha Roxb Pericarp

    Prashith Kekuda TR

    2012-03-01

    Full Text Available Artocarpus lakoocha Roxb is belongs to the family Moraceae and is called Monkey jack and Lakoocha. In the present study, we investigated elemental composition of fruit pericarp and anticariogenic, pancreatic lipase inhibitory and cytotoxic activity of methanol extract of pericarp. The elemental analysis was determined using atomic absorption spectrophotometer. Anticariogenic activity was determined against 12 isolates of mutans streptococci by Agar well diffusion method. Pancreatic lipase activity of different concentrations of pericarp extract was tested against chicken pancreatic lipase. Cytotoxic activity was tested by Brine shrimp lethality bioassay. Among the principal elements, potassium was present in high concentration followed by magnesium, phosphorus and calcium. Among trace elements, high concentration of iron was detected followed by zinc, manganese and copper. The extract caused inhibition of cariogenic bacteria and the inhibition caused by the extract was lesser when compared to standard antibiotic. The extract caused inhibition of pancreatic lipase in a dose dependent manner and highest inhibition (82.49% was observed at concentration 1000mg/ml. The lethal nature of extract towards brine shrimp was directly proportional to the concentration of the extract. The LC50 was found to be 452.49μg/ml. Preliminary phytochemical analysis showed the presence of tannins and alkaloids. The fruit may be consumed as a source of important elements. The bioactivities of the extract could be attributed to the presence of secondary metabolites. Further study is required to isolate and characterize the active constituents and to determine their bioactivities.

  11. Free Radical Scavenging and Alpha/Beta-glucosidases Inhibitory Activities of Rambutan (Nephelium lappaceum L. Peel Extract

    Wahyu Widowati

    2015-12-01

    Full Text Available BACKGROUND: Diabetes mellitus (DM is associated with oxidative reaction and hyperglycemic condition. Human body has an antioxidant defense system toward free radical, but overproduction of free radical causing imbalance condition between the free radical and the antioxidant defense in the body that lead to several diseases, including DM. Glucosidase is an enzyme that hydrolize carbohydrates causing increase of blood glucose level, so by inhibiting this enzyme blood glucose level in plasma could be effectively decreased. Rambutan (Nephelium lappaceum L. peel has been reported to have many potential roles, such as antioxidant and anti-glycemia. Therefore our current study was conducted to evaluate possible effectivity of Rambutan peel to scavenge free radical and to inhibit α- and β-glucosidases. METHODS: Rambutan peel extraction (RPE was performed based on maceration method. Geraniin was used as control. For antioxidant study, 2,2-diphenyl-1- picrylhydrazyl (DPPH free radical scavenging test was performed. For glucosidase inhibitory activity study,  α- and β-glucosidases inhibitory activity tests were performed. Results were analyzed for median of Inhibitory Concentration (IC50. RESULTS: The scavenging activity of RPE was comparable with Geraniin. Meanwhile, the α-glucosidase inhibitory activity of RPE was higher than the one of Geraniin. The α-glucosidase-inhibitory-activity IC50 of RPE and Geraniin were 0.106±0.080 μg/ml and 16.12±0.29 μg/ml, respectively. The β-glucosidase inhibitory activity of RPE was also higher than the one of Geraniin. The β-glucosidase-inhibitory-activity IC50 of RPE and Geraniin were 7.02±0.99 μg/ml and 19.81±0.66 μg/ml, respectively. CONCLUSIONS: Since RPE showed comparable free radical scavenging activity with Geraniin and higher α- and β-glucosidases inhibitory activities than Geraniin, RPE could be suggested as a promising antioxidant and antiglycemic agent.  KEYWORDS

  12. Enzyme inhibitory and antioxidant activities of traditional medicinal plants: Potential application in the management of hyperglycemia

    Gulati Vandana

    2012-06-01

    Full Text Available Abstract Background Traditional Indian and Australian medicinal plant extracts were investigated to determine their therapeutic potential to inhibit key enzymes in carbohydrate metabolism, which has relevance to the management of hyperglycemia and type 2 diabetes. The antioxidant activities were also assessed. Methods The evaluation of enzyme inhibitory activity of seven Australian aboriginal medicinal plants and five Indian Ayurvedic plants was carried out against α-amylase and α-glucosidase. Antioxidant activity was determined by measuring (i the scavenging effect of plant extracts against 2, 2-diphenyl-1-picryl hydrazyl (DPPH and 2, 2′-azinobis-3-ethylbenzothiazoline-6-sulfonate (ABTS and (ii ferric reducing power. Total phenolic and total flavonoid contents were also determined. Results Of the twelve plant extracts evaluated, the highest inhibitory activity against both α-amylase and α-glucosidase enzymes was exerted by Santalum spicatum and Pterocarpus marsupium with IC50 values of 5.43 μg/ml and 0.9 μg/ml, respectively, and 5.16 μg/ml and 1.06 μg/ml, respectively. However, the extracts of Acacia ligulata (IC50 = 1.01 μg/ml, Beyeria leshnaultii (0.39 μg/ml, Mucuna pruriens (0.8 μg/ml and Boerhaavia diffusa (1.72 μg/ml exhibited considerable activity against α-glucosidase enzyme only. The free radical scavenging activity was found to be prominent in extracts of Acacia kempeana, Acacia ligulata followed by Euphorbia drummondii against both DPPH and ABTS. The reducing power was more pronounced in Euphorbia drummondii and Pterocarpus marsupium extracts. The phenolic and flavonoid contents ranged from 0.42 to 30.27 μg/mg equivalent of gallic acid and 0.51 to 32.94 μg/mg equivalent of quercetin, respectively, in all plant extracts. Pearson’s correlation coefficient between total flavonoids and total phenolics was 0.796. Conclusion The results obtained in this study showed that most of the plant extracts

  13. Utilisation of rapeseed protein isolates for production of peptides with angiotensin I-converting enzyme (ACE-inhibitory activity

    Vioque, Javier

    2004-12-01

    Full Text Available ACE activity is related to increased arterial pressure and coronary diseases. A rapeseed protein isolate was hydrolyzed with the protease Alcalase in order to investigate the possible presence of ACE inhibitory peptides in the resulting hydrolysates. Hydrolysis for 30 min yielded a hydrolysate with the highest ACE inhibitory activity. Two fractions of this hydrolysate obtained by Biogel P2 gel filtration chromatography were used for further purification of ACE inhibitory peptides. Three fractions with ACE inhibitory activity were purified by reverse-phase HPLC of Biogel P2 f ractions. This demonstrates that rapeseed protein hydrolysates represent a good source of ACE inhibitory peptides .La actividad de ECA está relacionada con una presión arterial alta y enfermedades cardíacas. Un aislado proteico de colza se hidrolizó con alcalasa para estudiar la posible presencia de péptidos inhibidores de ECA en el hidrolizado. La hidrólisis durante 30 min produjo el hidrolizado con la mayor actividad inhibidora de ECA. Dos fracciones de este hidrolizado, obtenidas por cromatografía de filtración en gel Biogel P2, se usaron para la purificación de péptidos inhibidores de ECA. Tres fracciones con actividad inhibidora de ECA se purificaron mediante HPLC en fase reversa de las fracciones obtenidas mediante Biogel P2. Esto demuestra que los hidrolizados proteicos de colza representan una buena fuente de péptidos inhibidores de ECA.

  14. Angiotensin-I Converting Enzyme (ACE Inhibitory and Anti-Oxidant Activities of Sea Cucumber (Actinopyga lecanora Hydrolysates

    Raheleh Ghanbari

    2015-12-01

    Full Text Available In recent years, food protein-derived hydrolysates have received considerable attention because of their numerous health benefits. Amongst the hydrolysates, those with anti-hypertensive and anti-oxidative activities are receiving special attention as both activities can play significant roles in preventing cardiovascular diseases. The present study investigated the angiotensin-I converting enzyme (ACE inhibitory and anti-oxidative activities of Actinopyga lecanora (A. lecanora hydrolysates, which had been prepared by alcalase, papain, bromelain, flavourzyme, pepsin, and trypsin under their optimum conditions. The alcalase hydrolysate showed the highest ACE inhibitory activity (69.8% after 8 h of hydrolysis while the highest anti-oxidative activities measured by 2,2-diphenyl 1-1-picrylhydrazyl radical scavenging (DPPH (56.00% and ferrous ion-chelating (FIC (59.00% methods were exhibited after 24 h and 8 h of hydrolysis, respectively. The ACE-inhibitory and anti-oxidative activities displayed dose-dependent trends, and increased with increasing protein hydrolysate concentrations. Moreover, strong positive correlations between angiotensin-I converting enzyme (ACE inhibitory and anti-oxidative activities were also observed. This study indicates that A. lecanora hydrolysate can be exploited as a source of functional food owing to its anti-oxidant as well as anti-hypertension functions.

  15. Angiotensin-I Converting Enzyme (ACE) Inhibitory and Anti-Oxidant Activities of Sea Cucumber (Actinopyga lecanora) Hydrolysates.

    Ghanbari, Raheleh; Zarei, Mohammad; Ebrahimpour, Afshin; Abdul-Hamid, Azizah; Ismail, Amin; Saari, Nazamid

    2015-01-01

    In recent years, food protein-derived hydrolysates have received considerable attention because of their numerous health benefits. Amongst the hydrolysates, those with anti-hypertensive and anti-oxidative activities are receiving special attention as both activities can play significant roles in preventing cardiovascular diseases. The present study investigated the angiotensin-I converting enzyme (ACE) inhibitory and anti-oxidative activities of Actinopyga lecanora (A. lecanora) hydrolysates, which had been prepared by alcalase, papain, bromelain, flavourzyme, pepsin, and trypsin under their optimum conditions. The alcalase hydrolysate showed the highest ACE inhibitory activity (69.8%) after 8 h of hydrolysis while the highest anti-oxidative activities measured by 2,2-diphenyl 1-1-picrylhydrazyl radical scavenging (DPPH) (56.00%) and ferrous ion-chelating (FIC) (59.00%) methods were exhibited after 24 h and 8 h of hydrolysis, respectively. The ACE-inhibitory and anti-oxidative activities displayed dose-dependent trends, and increased with increasing protein hydrolysate concentrations. Moreover, strong positive correlations between angiotensin-I converting enzyme (ACE) inhibitory and anti-oxidative activities were also observed. This study indicates that A. lecanora hydrolysate can be exploited as a source of functional food owing to its anti-oxidant as well as anti-hypertension functions. PMID:26690117

  16. Green Synthesis and Urease Inhibitory Activity of Spiro-Pyrimidinethiones/Spiro-Pyrimidinones-Barbituric Acid Derivatives.

    Mohammadi Ziarani, Ghodsi; Asadi, Shima; Faramarzi, Sakineh; Amanlou, Massoud

    2015-01-01

    Sulfonic acid functionalized SBA-15 (SBA-Pr-SO3H) with pore size 6 nm as an efficient heterogeneous nanoporous solid acid catalyst exhibited good catalytic activity in the Biginelli-like reaction in the synthesis of spiroheterobicyclic rings with good yield and good recyclability. Spiro-pyrimidinethiones/spiro-pyrimidinones-barbituric acid derivatives were synthesized in a simple and efficient method using the one-pot three-component reaction of a cyclic 1,3- dicarbonyl compounds (barbituric acid), an aromatic aldehyde and urea or thiourea in the presence of nanoporous silica SBA-Pr-SO3H under solvent free conditions. Urease inhibitory activity of spiro compounds were tested against Jack bean urease using Berthelot alkaline phenol-hypochlorite method. Five of 13 compounds were inhibitor and two of them were enzyme activators. Analysis of the docking results showed that, in most of the spiro molecules, one of the carbonyl groups is coordinated with both nickel atoms, while the other one is involved in the formation of hydrogen bonds with important active-site residues. The effect of inserting two methyl groups on N atoms of barbiturate ring, S substituted, ortho, meta and para substituted compounds were investigated too. PMID:26664377

  17. Optimization of pancreatic lipase inhibitory and antioxidant activities of Ilex paraguariensis by using response surface methodology.

    Oh, Kyung-Eon; Shin, Hyeji; Jeon, Young Ho; Jo, Yang Hee; Lee, Mi Kyeong; Lee, Ken S; Park, Byoungduck; Lee, Ki Yong

    2016-07-01

    Response surface methodology (RSM) using a Box-Behnken design was used to optimize the extraction conditions for obtaining pancreatic lipase inhibitory and antioxidant principles from Ilex paraguariensis leaves. Three influencing factors: extraction time (min), the liquid-solid ratio, and ethanol concentration (%, v/v) were investigated in the ultrasonic extraction process. Optimization of the extraction conditions to obtain a product with minimum PL activity, maximum antioxidant activity, and maximum yield was performed using RSM by focusing on the three target influencing factors. The optimum conditions were established as the ethanol concentration (54.8 %), liquid-solid ratio (35.4), and extraction time (70.0 min). Under these conditions, the 2,2-diphenyl-1-picrylhydrazyl scavenging activity, PL activity, extraction yield were 59.3 ± 3.5, 35.3 ± 3.0, and 34.4 ± 0.4 %, respectively, similar to the theoretical predicted values of 59.7, 35.2, and 34.3 %, respectively. PMID:27277165

  18. Simultaneous quantitative analysis of 12 methoxyflavones with melanogenesis inhibitory activity from the rhizomes of Kaempferia parviflora.

    Ninomiya, Kiyofumi; Matsumoto, Taku; Chaipech, Saowanee; Miyake, Sohachiro; Katsuyama, Yushi; Tsuboyama, Akihiro; Pongpiriyadacha, Yutana; Hayakawa, Takao; Muraoka, Osamu; Morikawa, Toshio

    2016-04-01

    A methanol extract from the rhizomes of Kaempferia parviflora Wall. ex Baker (Zingiberaceae) has shown inhibitory effects against melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells (IC50 = 9.6 μg/mL). Among 25 flavonoids and three acetophenones isolated previously (1-28), several constituents including 5-hydroxy-7,3',4'-trimethoxyflavone (6, IC50 = 8.8 μM), 5,7,3',4'-tetramethoxyflavone (7, 8.6 μM), 5,3'-dihydroxy-3,7,4'-trimethoxyflavone (12, 2.9 μM), and 5-hydroxy-3,7,3',4'-tetramethoxyflavone (13, 3.5 μM) showed inhibitory effects without notable cytotoxicity at the effective concentrations. Compounds 6, 7, 12, and 13 inhibited the expression of tyrosinase, tyrosine-related protein (TRP)-1, and TRP-2 mRNA, which could be the mechanism of their melanogenesis inhibitory activity. In addition, a quantitative analytical method for 12 methoxyflavones (1, 2, 4-11, 13, and 14) in the extract was developed using HPLC. The optimal condition for separation and detection of these constituents were achieved on an ODS column (3 μm particle size, 2.1 mm i.d. × 100 mm) with MeOH-0.1 % aqueous acetic acid solvent systems as the mobile phase, and the detection and quantitation limits of the method were estimated to be 0.08-0.66 ng and 0.22-2.00ng, respectively. The relative standard deviation values of intra- and interday precision were lower than 0.95 and 1.08 %, respectively, overall mean recoveries of all flavonoids were 97.9-102.9 %, and the correlation coefficients of all the calibration curves showed good linearity within the test ranges. For validation of the protocol, extracts of three kinds of the plant's rhizomes collected from different regions in Thailand (Leoi, Phetchabun, and Chiang Mai provinces) were evaluated. The results indicated that the assay was reproducible, precise, and could be readily utilized for the quality evaluation of the plant materials. PMID:26711832

  19. Antioxidant, antibacterial and ACE-inhibitory activity of four monofloral honeys in relation to their chemical composition.

    León-Ruiz, Virginia; González-Porto, Amelia V; Al-Habsi, Nasser; Vera, Soledad; San Andrés, María Paz; Jauregi, Paula

    2013-11-01

    Different monofloral honeys from Castilla-La Mancha (Spain) have been studied in order to determine their main functional and biological properties. Thyme honey and chestnut honey possess the highest antioxidant capacity, which is due to their high vitamin C (in thyme honey) and total polyphenolic content (in chestnut honey). On the other hand, chestnut honey showed high antimicrobial activity against Staphylococcus aureus and Escherichia coli, whilst others had no activity against S. aureus and showed very small activity against E. coli. Moreover it was found that the antimicrobial activity measured in chestnut honey was partly due to its lysozyme content. In addition the angiotensin I-converting enzyme (ACE) inhibitory activity was measured, and the ACE inhibition is one mechanism by which antihypertensive activity is exerted in vivo. All the types of honey showed some activity but chestnut honey had the highest ACE inhibitory activity. PMID:24056722

  20. In silico docking studies and in vitro xanthine oxidase inhibitory activity of commercially available terpenoids

    MUTHUSWAMY UMAMAHESWARI

    2012-11-01

    Full Text Available Objective Xanthine oxidase is a highly versatile enzyme that is widely distributed among different species. The hydroxylation of purines is catalysed by xanthine oxidase and especially the conversion of xanthine to uric acid. Xanthine oxidase inhibitors are much useful, since they possess lesser side effects compared to uricosuric and anti-inflammatory agents. The present study deals with in silico and in vitro xanthine oxidase inhibitory analysis of commercially available terpenoids (bisabolol, β-caryophyllene, limonene, and α- terpinene. Methods Molecular docking studies were performed using AutoDock 4.2 and in vitro xanthine oxidase inhibitory activity was carried out using xanthine as the substrate. In addition, enzyme kinetics was performed using Lineweaver Burkplot analysis. Allopurinol, a known xanthine oxidase inhibitor was used as the standard. Results The results revealed that bisabolol exhibited a lowest binding energy value of about -7.33 kcal/mol. All other compounds showed binding energy values ranging between -7.33 to -5.87 kcal/mol which was less than the standard (-4.78 kcal/mol. In the xanthine oxidase assay, IC50 value of bisabolol was found to be 34.70 µg/ml, whereas that of allopurinol was 8.48 µg/ml. All the remaining compounds exhibited IC50 values ranging between 34.70 to 68.45 µg/ml.  In the enzyme kinetic studies, bisabolol, β-caryophyllene showed non competitive and Limonene, α- terpinene and allopurinol showed competitive type of enzyme inhibition. Conclusion It can be concluded that terpenoids could be a promising remedy for the treatment of gout and related inflammatory disorders. Further in vivo studies are required to develop potential compounds with lesser side effects.

  1. Acetylcholinesterase assay for cerebrospinal fluid using bupivacaine to inhibit butyrylcholinesterase

    Anders Jens

    2001-12-01

    Full Text Available Abstract Background Most test systems for acetylcholinesterase activity (E.C.3.1.1.7. are using toxic inhibitors (BW284c51 and iso-OMPA to distinguish the enzyme from butyrylcholinesterase (E.C.3.1.1.8. which occurs simultaneously in the cerebrospinal fluid. Applying Ellman's colorimetric method, we were looking for a non-toxic inhibitor to restrain butyrylcholinesterase activity. Based on results of previous in vitro studies bupivacaine emerged to be a suitable inhibitor. Results Pharmacokinetic investigations with purified cholinesterases have shown maximum inhibition of butyrylcholinesterase activity and minimal interference with acetylcholinesterase activity at bupivacaine final concentrations between 0.1 and 0.5 mmol/l. Based on detailed analysis of pharmacokinetic data we developed three equations representing enzyme inhibition at bupivacaine concentrations of 0.1, 0.2 and 0.5 mmol/l. These equations allow us to calculate the acetylcholinesterase activity in solutions containing both cholinesterases utilizing the extinction differences measured spectrophotometrically in samples with and without bupivacaine. The accuracy of the bupivacaine-inhibition test could be confirmed by investigations on solutions of both purified cholinesterases and on samples of human cerebrospinal fluid. If butyrylcholinesterase activity has to be assessed simultaneously an independent test using butyrylthiocholine iodide as substrate (final concentration 5 mmol/l has to be conducted. Conclusions The bupivacaine-inhibition test is a reliable method using spectrophotometrical techniques to measure acetylcholinesterase activity in cerebrospinal fluid. It avoids the use of toxic inhibitors for differentiation of acetylcholinesterase from butyrylcholinesterase in fluids containing both enzymes. Our investigations suggest that bupivacaine concentrations of 0.1, 0.2 or 0.5 mmol/l can be applied with the same effect using 1 mmol/l acetylthiocholine iodide as substrate.

  2. Antifungal and Zearalenone Inhibitory Activity of Pediococcus pentosaceus Isolated from Dairy Products on Fusarium graminearum.

    Sellamani, Muthulakshmi; Kalagatur, Naveen K; Siddaiah, Chandranayaka; Mudili, Venkataramana; Krishna, Kadirvelu; Natarajan, Gopalan; Rao Putcha, Venkata L

    2016-01-01

    The present study was aimed to evaluate the bio-control efficacy of Pediococcus pentosaceus isolated from traditional fermented dairy products originated from India, against the growth and zearalenone (ZEA) production of Fusarium graminearum. The cell-free supernatants of P. pentosaceus (PPCS) were prepared and chemical profiling was carried out by GC-MS and MALDI-TOF analysis. Chemical profiling of PPCS evidenced that, the presence of phenolic antioxidants, which are responsible for the antifungal activity. Another hand, MALDI-TOF analysis also indicated the presence of antimicrobial peptides. To know the antioxidant potential of PPCS, DPPH free radical scavenging assay was carried out and IC50 value was determined as 32 ± 1.89 μL/mL. The antifungal activity of P. pentosaceus was determined by dual culture overlay technique and zone of inhibition was recorded as 47 ± 2.81%, and antifungal activity of PPCS on F. graminearum was determined by micro-well dilution and scanning electron microscopic techniques. The minimum inhibitory concentration (MIC) of PPCS was determined as 66 ± 2.18 μL/mL in the present study. Also a clear variation in the micromorphology of mycelia treated with MIC value of PPCS compared to untreated control was documented. Further, the mechanism of growth inhibition was revealed by ergosterol analysis and determination of reactive oxygen species (ROS) in PPCS treated samples. The effects of PPCS on mycelial biomass and ZEA production were observed in a dose-dependent manner. The mechanism behind the suppression of ZEA production was studied by reverse transcriptase qPCR analysis of ZEA metabolic pathway genes (PKS4 and PKS13), and results showed that there is a dose dependent down-regulation of target gene expression in PPCS treated samples. The results of the present study were collectively proved that, the antifungal and ZEA inhibitory activity of PPCS against F. graminearum and it may find a potential application in agriculture and food

  3. Characterization and inhibitory activity of chitosan on hyphae growth and morphology of Botrytis cinerea plant pathogen

    Sebastião Silva Junior

    2014-07-01

    Full Text Available Summary. Low and high molecular weight chitosan were tested in different concentrations and growth times with the aim to evaluate the inhibitory activity against Botrytis cinerea, a very important plant pathogen. Tested chitosans were characterized by vibratory spectroscopy and elementary analyzes to determine the deacetylation degree. In addiction molar mass was estimated by viscosity measuring. Scanning electron microscopy was utilized for antimicrobial activity observation. Results showed that both chitosans markedly inhibited fungal growth, which was effected by incubation time and chitosan concentration. Scanning electron microscopy observations revealed that chitosan induced changes in surface morphology. The present study show that chitosan is capable of inhibit the growth and cause serious damage to the cell structure of the B. cinerea, as well as have the ability to form an impervious layer around the cell. Therefore, chitosan could be considered as a potential alternative for synthetic fungicides.Industrial relevance. Ultrastructural analysis showed that chitosan is capable of causing serious damage to the cell structure of the B. cinerea, as well as have the ability to form an impervious layer around the cell. Chitosan could inhibit the growth of B. cinerea in vitro and consequently may be considered as a potential alternative in replacement of synthetic fungicides.Keywords. biopolymer; chitosan; antifungal activity; fungal morphology; electron microscopy

  4. Four new ginsenosides from red ginseng with inhibitory activity on melanogenesis in melanoma cells.

    Zhou, Qi-Le; Yang, Xiu-Wei

    2015-08-15

    During a search for novel melanogenesis inhibitors originating from nature sources, four new ginsenosides, including three dammarane-type triterpenoid saponins, 20(S)-ginsenoside-Rf-1a (1), 20Z-ginsenoside-Rs4 (2), 23-O-methylginsenoside-Rg11 (3), and one oleanane-type saponin, ginsenoside-Ro-6'-O-butyl ester (4) were isolated from red ginseng (the steamed ginseng) to evaluate their protective effects against melanogenesis. Compounds 2 and 3 exhibited potent inhibitory effects against both melanin synthesis and tyrosinase activity in a dose-dependent manner in the α-MSH-stimulated B16 melanoma cells, and were more potent than the positive control arbutin, a well-known tyrosinase inhibitor. The results indicated that just the two carbon-20(22) double-bond-type ginsenosides showed strong inhibiting activity on melanogenesis through reducing tyrosinase activity. Thus, ginsenosides with such similar chemical structure in red ginseng may be potential natural products as tyrosinase inhibitors against malignant melanoma. PMID:26087936

  5. Inhibitory activities of soluble and bound millet seed phenolics on free radicals and reactive oxygen species.

    Chandrasekara, Anoma; Shahidi, Fereidoon

    2011-01-12

    Oxidative stress, caused by reactive oxygen species (ROS), is responsible for modulating several pathological conditions and aging. Soluble and bound phenolic extracts of commonly consumed millets, namely, kodo, finger (Ravi), finger (local), foxtail, proso, little, and pearl, were investigated for their phenolic content and inhibition of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and ROS, namely, hydroxyl radical, peroxyl radical, hydrogen peroxide (H(2)O(2)), hypochlorous acid (HOCl), and singlet oxygen ((1)O(2)). Inhibition of DPPH and hydroxyl radicals was detrmined using electron paramagnetic resonance (EPR) spectroscopy. The peroxyl radical inhibitory activity was measured using the oxygen radical absorbance capacity (ORAC) assay. The scavenging of H(2)O(2), HOCl, and (1)O(2) was evaluated using colorimetric methods. The results were expressed as micromoles of ferulic acid equivalents (FAE) per gram of grain on a dry weight basis. In addition, major hydroxycinnamic acids were identified and quantified using high-performance liquid chromatography (HPLC) and HPLC-mass spectrometry (MS). All millet varieties displayed effective radical and ROS inhibition activities, which generally positively correlated with phenolic contents, except for hydroxyl radical. HPLC analysis revealed the presence of ferulic and p-coumaric acids as major hydroxycinnamic acids in phenolic extract and responsible for the observed effects. Bound extracts of millet contributed 38-99% to ROS scavenging, depending on the variety and the test system employed. Hence, bound phenolics must be included in the evaluation of the antioxidant activity of millets and other cereals. PMID:21133411

  6. Limonoids from the seeds of Swietenia macrophylla with inhibitory activity against dengue virus 2.

    Cheng, Yuan-Bin; Chien, Yi-Ting; Lee, Jin-Ching; Tseng, Chin-Kai; Wang, Hui-Chun; Lo, I-Wen; Wu, Yi-Hung; Wang, Sheng-Yang; Wu, Yang-Chang; Chang, Fang-Rong

    2014-11-26

    Fractionation of an ethanol-soluble extract of the seeds of Swietenia macrophylla yielded six new limonoids, swielimonoids A-F (1-6), along with 20 known compounds. Compounds 1 and 2, mexicanolide-type limonoids, were assigned with an α,β-unsaturated δ-lactone moiety (ring D) and a C═C bond between C-8 and C-30. Compounds 3-6 could be categorized as highly oxygenated phragmalin-type limonoids. The structures of these new compounds were elucidated through the interpretation of spectroscopic data. The antidengue virus 2 activities of the isolated components from S. macrophylla were investigated, and of 12 compounds subjected to bioassay, compounds 2 and 7-10 were found to show inhibitory activity in the range 3.5 to 12.5 μM. Among these, the new limonoid 2 exhibited significant antiviral activity (EC50 = 7.2 ± 1.33 μM) with a selectivity index (CC50/EC50) value of >27.7. PMID:25330401

  7. Tyrosinase Inhibitory Activity, 3D QSAR, and Molecular Docking Study of 2,5-Disubstituted-1,3,4-Oxadiazoles

    Ramesh L. Sawant

    2013-01-01

    Full Text Available In continuation with our research program, in search of potent enzyme tyrosinase inhibitor, a series of synthesized 2,5-disubstituted 1,3,4-oxadiazoles have been evaluated for enzyme tyrosinase inhibitory activity. Subsequently, 3D QSAR and docking studies were performed to find optimum structural requirements for potent enzyme tyrosinase inhibitor from this series. The synthesized 20 compounds of 2,5-disubstituted-1,3,4-oxadiazole series were screened for mushroom tyrosinase inhibitory activity at various concentrations by enzyme inhibition assay. The percentage enzyme inhibition was calculated by recording absorbance at 492 nm with microplate reader. 3D QSAR and docking studies were performed using VLife MDS 3.5 software. In the series 2,5-disubstituted-1,3,4-oxadiazoles enzyme tyrosinase inhibitory activity was found to be dose dependent with maximum activity for compounds 4c, 4h, 4m, and 4r. 3D QSAR and docking studies revealed that more electropositive and less bulky substituents if placed on 1,3,4-oxadiazole nucleus may result in better tyrosinase inhibitory activity in the series.

  8. Synthesis of 1-[11c]methylpiperidin-4-yl propionate ([11c]pmp) for in vivo measurements of acetylcholinesterase activity

    Synthesis of 1-[11C]methylpiperidin-4-yl propionate ([11C]PMP), an in vivo substrate for acetylcholinesterase, is reported. An improved preparation of 4-piperidinyl propionate (PHP), the immediate precursor for radiolabeling, was accomplished in three steps from 4-hydroxypiperidine by (a) protection of the amine as the benzyl carbamate, (b) acylation with propionyl chloride, and (c) deprotection of the carbamate by catalytic hydrogenation. The final product was obtained in an overall 82% yield. Reaction of the free base form of PHP with [11C]methyl trifluoromethanesulfonate at room temperature in N,N-dimethylformamide, followed by high performance liquid chromatography (HPLC) purification, provided [11C]PMP in 57% radiochemical yield, >99% radiochemical purity, and >1500 Ci/mmol at the end of synthesis. The total synthesis time from end-of-bombardment was 35 min. [11C]PMP can thus be reliably prepared for routine clinical studies of acetylcholinesterase in human brain using positron emission tomography

  9. Central and direct regulation of testicular activity by gonadotropin-inhibitory hormone and its receptor

    KazuyoshiTsutsui

    2014-01-01

    Full Text Available Gonadotropin-inhibitory hormone (GnIH was first identified in Japanese quail to be an inhibitor of gonadotropin synthesis and release. GnIH peptides have since been identified in all vertebrates, and all share an LPXRFamide (X = L or Q motif at their C-termini. The receptor for GnIH is the G protein-coupled receptor 147 (GPR147, which inhibits cAMP signaling. Cell bodies of GnIH neurons are located in the paraventricular nucleus (PVN in birds and the dorsomedial hypothalamic area (DMH in most mammals. GnIH neurons in the PVN or DMH project to the median eminence to control anterior pituitary function via GPR147 expressed in gonadotropes. Further, GnIH inhibits gonadotropin-releasing hormone (GnRH -induced gonadotropin subunit gene transcription by inhibiting the adenylate cyclase/cAMP/PKA -dependent ERK pathway in an immortalized mouse gonadotrope cell line (LT2 cells. GnIH neurons also project to GnRH neurons that express GPR147 in the preoptic area (POA in birds and mammals. Accordingly, GnIH can inhibit gonadotropin synthesis and release by decreasing the activity of GnRH neurons as well as by directly inhibiting pituitary gonadotrope activity. GnIH and GPR147 can thus centrally suppress testosterone secretion and spermatogenesis by acting in the hypothalamic-pituitary-gonadal axis. GnIH and GPR147 are also expressed in the testis of birds and mammals, possibly acting in an autocrine/paracrine manner to suppress testosterone secretion and spermatogenesis. GnIH expression is also regulated by melatonin, stress and social environment in birds and mammals. Accordingly, the GnIH-GPR147 system may play a role in transducing physical and social environmental information to regulate optimal testicular activity in birds and mammals. This review discusses central and direct inhibitory effects of GnIH and GPR147 on testosterone secretion and spermatogenesis in birds and mammals.

  10. Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities

    N A Hanapi

    2013-01-01

    Full Text Available Context: To date, many findings reveal that most of the modern drugs have the ability to interact with herbal drugs. Aims: This study was conducted to determine the inhibitory effects of mitragynine on cytochrome P450 2C9, 2D6 and 3A4 activities. Methods and Material: The in vitro study was conducted using a high-throughput luminescence assay. Statistical Analysis: Statistical analysis was conducted using one-way ANOVA and Dunnett′s test with P < 0.05 vs. control. The IC 50 values were calculated using the GraphPad Prism® 5 (Version 5.01, GraphPad Software, Inc., USA. Results: Assessment using recombinant enzymes showed that mitragynine gave the strongest inhibitory effect on CYP2D6 with an IC 50 value of 0.45±0.33 mM, followed by CYP2C9 and CYP3A4 with IC 50 values of 9.70±4.80 and 41.32±6.74 mM respectively. Positive inhibitors appropriate for CYP2C9, CYP2D6, and CYP3A4 which are sulfaphenazole, quinidine and ketoconazole were used respectively. V max values of CYP2C9, CYP2D6 and CYP3A4 were 0.0005, 0.01155 and 0.0137 mM luciferin formed/pmol/min respectively. K m values of CYP2C9, CYP2D6, and CYP3A4 were 32.65, 56.01, and 103.30 mM respectively. Mitragynine noncompetitively inhibits CYP2C9 and CYP2D6 activities with the K i values of 61.48 and 12.86 mM respectively. On the other hand, mitragynine inhibits CYP3A4 competitively with a K i value of 379.18 mM. Conclusions: The findings of this study reveal that mitragynine might inhibit cytochrome P450 enzyme activities, specifically CYP2D6. Therefore, administration of mitragynine together with herbal or modern drugs which follow the same metabolic pathway may contribute to herb-drug interactions.

  11. [Constituents relating to anti-oxidative and alpha-glucosidase inhibitory activities in Yacon aerial part extract].

    Terada, Sumio; Ito, Kikuo; Yoshimura, Akira; Noguchi, Naoto; Ishida, Takashi

    2006-08-01

    Hot water extract of the aerial part of Yacon (Smallanthus sonchifolia, Compositae) showed potent free radical-scavenging activity and inhibitory effects on lipid peroxidation in rat brain homogenate. The most potent antioxidative activity focused on the 50% MeOH-eluted fraction on DIAION HP-20 column chromatography. The structure of the major component in the fraction was identified as 2,3,5-tricaffeoylaltraric acid (TCAA) based on spectroscopic evidence. The antioxidative activity of TCAA is superior to that of natural antioxidants such as (+/-)-catechin, alpha-tocopherol, and ellagic acid, and TCAA also showed selective maltase-inhibitory activity (IC(50) 49 microg/ml). As the hypoglycemic activity of Yacon extract was described in a previous report, the present results showing that the aerial part of Yacon has strong antioxidative activity may encourage its potential use as a food supplement to prevent type II diabetes. PMID:16880725

  12. Inhibitory Activity of Synthesized Acetylated Procyanidin B1 Analogs against HeLa S3 Cells Proliferation

    Syuhei Okamoto

    2014-02-01

    Full Text Available Proanthocyanidins, also known as condensed tannins and/or oligomeric flavonoids, occur in many edible plants and have various interesting biological activities. Previously, we reported a synthetic method for the preparation of various procyanidins in pure form and described their biological activities. Here, we describe the synthesis of procyanidin B1 acetylated analogs and discuss their inhibition activities against HeLa S3 cell proliferation. Surprisingly, the lower-unit acetylated procyanidin B1 strongly inhibited the proliferation of HeLa S3 cells. This molecule showed much stronger inhibitory activity than did epigallocatechin-3-O-gallate (EGCG, green tea polyphenol, and dimeric compounds that included EGCG as a unit. This result suggests that the phenolic hydroxyl groups of the upper-units in flavan-3-ols are important for their inhibitory activity against cancer cell proliferation and that a hydrophobic lower unit dimer enhances this activity.

  13. Acetylcholinesterase and Butyrylcholinesterase Inhibitory Compounds from Corydalis cava (Fumariaceae)

    Chlebek, J.; Macáková, K.; Cahlíková, L.; Kurfürst, Milan; Kuneš, J.; Opletal, J.

    2011-01-01

    Roč. 6, č. 5 (2011), s. 607-610. ISSN 1934-578X Institutional research plan: CEZ:AV0Z40720504 Keywords : corydalis cava * fumariaceae * alzheimer ´s disease Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 1.242, year: 2011

  14. Chemical Characterization and Acetylcholinesterase Inhibition Potential of Volatile Components of Aerial Parts of Pluchea lanceolata (DC. Oliv. & Hiern

    Pooja Srivastava

    2015-06-01

    Full Text Available Pluchea lanceolata (DC. Oliv. & Hiern (Rasana is an important medicinal plant due to its usage in number of Ayurvedic formulations. First time, chemical composition of essential oil from the aerial part of P. lanceolata was analyzed by gas chromatography-mass spectrometry (GC-MS and NMR spectroscopy. Ex-vivo cholinesterase inhibitory activity of the essential oil was also evaluated using mouse brain homogenate. The major components were linalool (32.2%, β-caryophyllene (8.5%, α-terpineol (8.0%, spathulenol (7.4%, linalylacetate (5.6%, naphthalene, 1,6-dimethyl-4-(1-methylethyl- (4.3%, α-copaene (3.6%, epi-cubebol (3.6% and trans-α-bergamontene (3.1%. The experimental results showed that hydrodistilate of P. lanceolata significantly inhibited acetylcholinesterase activity (IC 50 value 2.54 ± 0.03 µg/mL.

  15. Lanostane triterpenoids from Ganoderma curtisii and their NO production inhibitory activities of LPS-induced microglia.

    Jiao, Yang; Xie, Ting; Zou, Lu-Hui; Wei, Qian; Qiu, Li; Chen, Li-Xia

    2016-08-01

    Twenty-nine lanostane triterpenoids (1-29) were obtained from the EtOH extract of fruiting bodies of the Ganoderma curtisii. Among them, compound 1 was a new lanostane triterpenoid and compounds 2-5 were isolated from the genus Ganoderma for the first time and their structures were unambiguously identified in this work. The NMR data of the four known lanostane triterpenoids (2-5) were reported for the first time because their structures were all tentatively characterized by interpreting the MS data from the methanol extract of Ganoderma lucidum or from the metabolites in rat bile after oral administration of crude extract of the fruiting bodies of G. lucidum using fragmentation rules. Their anti-inflammatory activities were tested by measuring their inhibitory effects on nitric oxide (NO) production in BV-2 microglia cells activated by lipopolysaccharide. Their IC50 values were in a range from 3.65±0.41 to 28.04±2.81μM. PMID:27335254

  16. Leukemia inhibitory factor promote trophoblast invasion via urokinase-type plasminogen activator receptor in preeclampsia.

    Zheng, Qin; Dai, Kuixing; Cui, Xinyuan; Yu, Ming; Yang, Xuesong; Yan, Bin; Liu, Shuai; Yan, Qiu

    2016-05-01

    Preeclampsia is a pregnancy-related syndrome which can cause perinatal mortality and morbidity. Inadequate invasion by trophoblast cells may lead to poor perfusion of the placenta, even result in preeclampsia. Understanding the molecular mechanisms underlying placentation facilitates the better intervention of preeclampsia. Urokinase-type plasminogen activator receptor (uPAR) is involved in the physiological and pathological processes. Leukemia inhibitory factor (LIF) is an important regulator in the establishment of pregnancy. However, the expression of uPAR in preeclamptic patients and its relationship with LIF remains unclear. In the current study, we found that the level of uPAR was relatively lower in the placentas from preeclamptic patients as compared with normal pregnant women. LIF promoted trophoblast cell outgrowth by upregulating uPAR in an explants culture, and LIF also enhanced migration and invasion potential through uPAR in trophoblast JAR and JEG-3 cell lines, and with increased gelatinolytic activities of matrix metalloproteinase 2 (MMP-2). The effect of LIF and uPAR on trophoblast migration and invasion was mediated by PI3K/AKT signaling pathway. Our data indicates the roles of LIF in promoting trophoblast migration and invasion through uPAR and suggest that abnormal expression of uPAR might be associated with the etiology of preeclampsia. PMID:27133045

  17. Structure-activity relationships of vanillic acid ester analogs in inhibitory effect of antigen-mediated degranulation in rat basophilic leukemia RBL-2H3 cells.

    Ishimata, Nao; Ito, Hideyuki; Tai, Akihiro

    2016-08-01

    Methyl vanillate (1) showed strong degranulation inhibitory activity among vanillin derivatives tested. In order to find structure-activity relationships for developing anti-allergic agents with simple structures and potent activity, we synthesized several vanillic acid (VA) ester derivatives with C1-C4 and C8 alkyl chains and evaluated their degranulation inhibitory activities. The most active compound of VA ester derivatives was derivative 5 with a C4 straight alkyl chain, and derivative 5 exhibited approximately three-fold greater inhibitory activity than that of 1. Moreover, we designed 8 types of analogs based on 5, and we found that the minimum structure for potent degranulation inhibitory activity requires direct connection of the butyl ester moiety on the benzene ring and at least one hydroxyl group on the benzene ring. Butyl meta or para hydroxyl benzoate (10 or 11) has a simpler structure than that of 5 and exhibited more potent degranulation inhibitory activity than that of 5. PMID:27324979

  18. Inhibitory Activity of Yokukansankachimpihange against Nerve Growth Factor-Induced Neurite Growth in Cultured Rat Dorsal Root Ganglion Neurons.

    Murayama, Chiaki; Watanabe, Shimpei; Nakamura, Motokazu; Norimoto, Hisayoshi

    2015-01-01

    Chronic pruritus is a major and distressing symptom of many cutaneous diseases, however, the treatment remains a challenge in the clinic. The traditional Chinese-Japanese medicine (Kampo medicine) is a conservative and increasingly popular approach to treat chronic pruritus for both patients and medical providers. Yokukansankachimpihange (YKH), a Kampo formula has been demonstrated to be effective in the treatment of itching of atopic dermatitis in Japan although its pharmacological mechanism is unknown clearly. In an attempt to clarify its pharmacological actions, in this study, we focused on the inhibitory activity of YKH against neurite growth induced with nerve growth factor (NGF) in cultured rat dorsal root ganglion (DRG) neurons because epidermal hyperinnervation is deeply related to itch sensitization. YKH showed approximately 200-fold inhibitory activity against NGF-induced neurite growth than that of neurotropin (positive control), a drug used clinically for treatment of chronic pruritus. Moreover, it also found that Uncaria hook, Bupleurum root and their chemical constituents rhynchophylline, hirsutine, and saikosaponin a, d showed inhibitory activities against NGF-induced neurite growth, suggesting they should mainly contribute to the inhibitory activity of YKH. Further study on the effects of YKH against epidermal nerve density in "itch-scratch" animal models is under investigation. PMID:26287150

  19. Repressors report fewer intrusions following a laboratory stressor : The role of reduced stressor-relevant concept activation and inhibitory functioning

    Overwijk, Sippie; Wessel, Ineke; de Jong, Peter J.

    2009-01-01

    This study investigated whether a repressive coping style is associated with fewer intrusions following an experimentally controlled stressor. Furthermore, we examined whether lower activation of stressor-relevant concepts in long-term memory and better inhibitory functioning may contribute to this

  20. Molecular characterization and chromosomal assignment of equine cartilage derived retinoic acid sensitive protein (CD-RAP)/melanoma inhibitory activity (MIA)

    Berg, Lise Charlotte; Mata, Xavier; Thomsen, Preben Dybdahl

    2008-01-01

    Cartilage-derived retinoic acid sensitive protein (CD-RAP) also known as melanoma inhibitory activity (MIA) has already been established as a marker for chondrocyte differentiation and a number of cancerous condition sin humans. Studies have also shown that CD-RAP/MIA is a potential marker of joi...

  1. Effects of Heat, pH, and Gamma Irradiation Treatments on Lipase Inhibitory Activity of Sargassum thunbergii Ethanol Extract

    Inhibitory activity of Sagassum thunbergii (ST) against porcine pancreatic lipase was assessed after heat treatment, pH changes, and gamma irradiation. This analysis revealed that the ST ethanol extract exhibited high lipase inhibitory activity (37.37%) at 5 mg/mL. The ST ethanol extract was treated with heat at 60°C for 10, 30, and 60 min; 80 and 100°C for 10 and 20 min; and 121°C for 15 min, pH (2, 4, 6, 8 and 10) and γ -irradiation (3, 7 and 20 kGy). The lipase inhibitory activity of the ST ethanol extract increased in all heat treatments, especially at 121°C for 15 min (51.55%) compared with the control. With regard to pH stability, the ST ethanol extract showed no significant changes at pH 4 ~ 8, but somewhat decreased inhibitory activity was revealed at pH 2 (26.25%) and 10 (29.93%). On the other hand, the ST ethanol extract was not affected by γ -irradiation treatment conditions used in this study. These results suggest that ST has a potential role as a functional food agent. (author)

  2. Inhibitory Activity of Yokukansankachimpihange against Nerve Growth Factor-Induced Neurite Growth in Cultured Rat Dorsal Root Ganglion Neurons

    Chiaki Murayama

    2015-08-01

    Full Text Available Chronic pruritus is a major and distressing symptom of many cutaneous diseases, however, the treatment remains a challenge in the clinic. The traditional Chinese-Japanese medicine (Kampo medicine is a conservative and increasingly popular approach to treat chronic pruritus for both patients and medical providers. Yokukansankachimpihange (YKH, a Kampo formula has been demonstrated to be effective in the treatment of itching of atopic dermatitis in Japan although its pharmacological mechanism is unknown clearly. In an attempt to clarify its pharmacological actions, in this study, we focused on the inhibitory activity of YKH against neurite growth induced with nerve growth factor (NGF in cultured rat dorsal root ganglion (DRG neurons because epidermal hyperinnervation is deeply related to itch sensitization. YKH showed approximately 200-fold inhibitory activity against NGF-induced neurite growth than that of neurotropin (positive control, a drug used clinically for treatment of chronic pruritus. Moreover, it also found that Uncaria hook, Bupleurum root and their chemical constituents rhynchophylline, hirsutine, and saikosaponin a, d showed inhibitory activities against NGF-induced neurite growth, suggesting they should mainly contribute to the inhibitory activity of YKH. Further study on the effects of YKH against epidermal nerve density in “itch-scratch” animal models is under investigation.

  3. Angiotensin-I Converting Enzyme (ACE) Inhibitory and Anti-Oxidant Activities of Sea Cucumber (Actinopyga lecanora) Hydrolysates

    Raheleh Ghanbari; Mohammad Zarei; Afshin Ebrahimpour; Azizah Abdul-Hamid; Amin Ismail; Nazamid Saari

    2015-01-01

    In recent years, food protein-derived hydrolysates have received considerable attention because of their numerous health benefits. Amongst the hydrolysates, those with anti-hypertensive and anti-oxidative activities are receiving special attention as both activities can play significant roles in preventing cardiovascular diseases. The present study investigated the angiotensin-I converting enzyme (ACE) inhibitory and anti-oxidative activities of Actinopyga lecanora (A. lecanora) hydrolysates,...

  4. Investigation of aromatase inhibitory activity of metal complexes of 8-hydroxyquinoline and uracil derivatives

    Prachayasittikul V

    2014-08-01

    Full Text Available Veda Prachayasittikul,1 Ratchanok Pingaew,2 Chanin Nantasenamat,3 Supaluk Prachayasittikul,3 Somsak Ruchirawat,4,5 Virapong Prachayasittikul1 1Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand; 2Department of Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok, Thailand; 3Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand; 4Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, 5Chulabhorn Graduate Institute, Bangkok, Thailand Purpose: Estrogens play important roles in the pathogenesis and progression of breast cancer as well as estrogen-related diseases. Aromatase is a key enzyme in the rate-limiting step of estrogen production, in which its inhibition is one strategy for controlling estrogen levels to improve prognosis of estrogen-related cancers and diseases. Herein, a series of metal (Mn, Cu, and Ni complexes of 8-hydroxyquinoline (8HQ and uracil derivatives (4–9 were investigated for their aromatase inhibitory and cytotoxic activities. Methods: The aromatase inhibition assay was performed according to a Gentest™ kit using CYP19 enzyme, wherein ketoconazole and letrozole were used as reference drugs. The cytotoxicity was tested on normal embryonic lung cells (MRC-5 using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Results: Only Cu complexes (6 and 9 exhibited aromatase inhibitory effect with IC50 0.30 and 1.7 µM, respectively. Cytotoxicity test against MRC-5 cells showed that Mn and Cu complexes (5 and 6, as well as free ligand 8HQ, exhibited activity with IC50 range 0.74–6.27 µM. Conclusion: Cu complexes (6 and 9 were found to act as a novel class of aromatase inhibitor. Our findings suggest that these 8HQ–Cu–uracil complexes are promising agents that could be potentially developed as a selective anticancer agent for breast cancer

  5. Study on the Antimicrobial activity and Minimum Inhibitory Concentration of Essential Oils of Spices

    R.V.N.Srujan and M.Sravanthi

    Full Text Available Antibacterial activity and minimum inhibitory concentration (MIC of essential oils of garlic, clove and cinnamon were estimated by using various bacterial pathogens. Among the bacterial pathogens tested against essential oil of garlic, Staphylococcus aureus was found to be highly sensitive followed by E.coli. L.monocytogenes and S.pyogenes were found to be less sensitive. The essential oil of clove was found to be most active against S.aureus followed by E.coli. B.cereus and C. jejuni. The essential oil of cinnamon was also most active against S.aureus followed by E.coli and C.jejuni. Essential oil of cinnamon was found to be active against all the bacterial pathogens tested, when compared to garlic and clove oils. However Staph. aureus, E. coli and C.jejuni were found to be most sensitive to the action of essential oils of garlic, clove and cinnamon. Among the bacterial pathogens tested against essential oils of spices to know the MIC by agar diffusion method, C.jejuni was found to be most sensitive to the essential oil of garlic followed by E.coli, S. typhimurium and Staphylococcus aureus. L. monocytogenes and Methicillin resistant Staph. aureus were found to be comparatively less sensitive. Essential oil of clove was also found to be highly effective against C.jejuni followed by E.coli, S.typhimurium and S.aureus. Again L.monocytogenes and Methicillin resistant S.aureus were comparatively less sensitive to the action of essential oil of clove. All most all the bacterial pathogens tested were found to be sensitive to the essential oil of cinnamon. However C.jejuni and E.coli were found to be most sensitive followed by S.typhimurium, Staph. aureus and Methicillin resistant Staph. aureus . [Vet. World 2011; 4(7.000: 311-316

  6. Inhibitory effect of putranjivain A on allergic inflammation through suppression of mast cell activation

    A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. Putranjivain A (PJA), member of ellagitannin, is known to possess beneficial effects including anti-cancer and anti-viral activities. The aim of the present study was to elucidate whether PJA modulates the allergic inflammatory reaction and to study its possible mechanisms of action using mast cell-based in vitro and in vivo models. The study was performed in anaphylaxis mouse model and cultured mast cells. PJA inhibited the expression of pro-inflammatory cytokines in immunoglobulin E-stimulated mast cells. PJA reduced this expression by inhibiting nuclear factor (NF)-κB and nuclear factor of activated T cell. The oral administration of PJA reduced systemic and cutaneous anaphylaxis, the release of serum histamine, and the expression of the histamine H1 receptor. In addition, PJA attenuated the activation of mast cells. PJA inhibited the release of histamine from various types of mast cells by the suppression of intracellular calcium. The inhibitory activity of PJA on the allergic reaction was similar to that of disodium cromoglycate, a known anti-allergic drug. These results suggest that PJA can facilitate the prevention or treatment of allergic inflammatory diseases mediated by mast cells. - Highlights: • PJA reduced the degranulation of mast cells. • PJA inhibited the production of inflammatory cytokines. • The effect of PJA on allergic reaction was comparable to the DSCG. • PJA might be a candidate for the treatment of allergic inflammatory diseases

  7. Inhibitory effect of putranjivain A on allergic inflammation through suppression of mast cell activation

    Kim, Hui-Hun; Park, Seung-Bin; Lee, Soyoung [CMRI, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Kwon, Taeg Kyu [Department of Immunology, School of Medicine, Keimyung University, Daegu 704-701 (Korea, Republic of); Shin, Tae-Yong [College of Pharmacy, Woosuk University, Jeonju 565-701 (Korea, Republic of); Park, Pil-Hoon; Lee, Seung-Ho [College of Pharmacy, Youngnam University, Kyungsan 712-749 (Korea, Republic of); Kim, Sang-Hyun, E-mail: shkim72@knu.ac.kr [CMRI, Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of)

    2014-02-01

    A great number of people are suffering from allergic inflammatory disease such as asthma, atopic dermatitis, and sinusitis. Therefore discovery of drugs for the treatment of these diseases is an important subject in human health. Putranjivain A (PJA), member of ellagitannin, is known to possess beneficial effects including anti-cancer and anti-viral activities. The aim of the present study was to elucidate whether PJA modulates the allergic inflammatory reaction and to study its possible mechanisms of action using mast cell-based in vitro and in vivo models. The study was performed in anaphylaxis mouse model and cultured mast cells. PJA inhibited the expression of pro-inflammatory cytokines in immunoglobulin E-stimulated mast cells. PJA reduced this expression by inhibiting nuclear factor (NF)-κB and nuclear factor of activated T cell. The oral administration of PJA reduced systemic and cutaneous anaphylaxis, the release of serum histamine, and the expression of the histamine H{sub 1} receptor. In addition, PJA attenuated the activation of mast cells. PJA inhibited the release of histamine from various types of mast cells by the suppression of intracellular calcium. The inhibitory activity of PJA on the allergic reaction was similar to that of disodium cromoglycate, a known anti-allergic drug. These results suggest that PJA can facilitate the prevention or treatment of allergic inflammatory diseases mediated by mast cells. - Highlights: • PJA reduced the degranulation of mast cells. • PJA inhibited the production of inflammatory cytokines. • The effect of PJA on allergic reaction was comparable to the DSCG. • PJA might be a candidate for the treatment of allergic inflammatory diseases.

  8. Extracts from Traditional Chinese Medicinal Plants Inhibit Acetylcholinesterase, a Known Alzheimer’s Disease Target

    Dorothea Kaufmann

    2016-08-01

    Full Text Available Inhibition of acetylcholinesterase (AChE is a common treatment for early stages of the most general form of dementia, Alzheimer’s Disease (AD. In this study, methanol, dichloromethane and aqueous crude extracts from 80 Traditional Chinese Medical (TCM plants were tested for their in vitro anti-acetylcholinesterase activity based on Ellman’s colorimetric assay. All three extracts of Berberis bealei (formerly Mahonia bealei, Coptis chinensis and Phellodendron chinense, which contain numerous isoquinoline alkaloids, substantially inhibited AChE. The methanol and aqueous extracts of Coptis chinensis showed IC50 values of 0.031 µg/mL and 2.5 µg/mL, therefore having an up to 100-fold stronger AChE inhibitory activity than the already known AChE inhibitor galantamine (IC50 = 4.33 µg/mL. Combinations of individual alkaloids berberine, coptisine and palmatine resulted in a synergistic enhancement of ACh inhibition. Therefore, the mode of AChE inhibition of crude extracts of Coptis chinensis, Berberis bealei and Phellodendron chinense is probably due to of this synergism of isoquinoline alkaloids. All extracts were also tested for their cytotoxicity in COS7 cells and none of the most active extracts was cytotoxic at the concentrations which inhibit AChE. Based on these results it can be stated that some TCM plants inhibit AChE via synergistic interaction of their secondary metabolites. The possibility to isolate pure lead compounds from the crude extracts or to administer these as nutraceuticals or as cheap alternative to drugs in third world countries make TCM plants a versatile source of natural inhibitors of AChE.

  9. Promotion and computation of inhibitory effect on tyrosinase activity of herbal cream by incorporating indigenous medicinal plants.

    Sahu, Ram Kumar; Roy, Amit; Dwivedi, Jaya; Jha, Arvind Kumar

    2014-01-01

    Herbal cream imparts a chief role in regulating melanin production of skin. The phytoconstituents present in herbal cream impact biological functions of skin and contribute nutrients required for the healthy skin. In the present study, it was envisaged to prepare three batches of herbal cream (HC1, HC2 and HC3) containing ethanol extracts of Emblica officinalis (fruits), Daucus carota (root), Mangifera indica (leaves), Mentha arvensis (leaves), Terminalia arjuna (bark) and Cucumis sativus (fruits) and investigated the prepared cream for inhibitory effect on tyrosinase activity. The herbal cream was formulated by incorporating different ratio of extracts, by using cream base. Each formulation HC1, HC2 and HC3 were segregated into three different formulations (HC1.1, HC1.2, HC1.3, HC2.1, HC2.2, HC2.3, HC3.1, HC3.2 and HC3.3) by incorporating increasing ratio of extract in formulation. The HC3.2 cream produces highest tyrosinase inhibitory effect 65.23 +/- 0.07%, while the HC2.1 exhibited minimum tyrosinase inhibitory effect 26.19 +/- 0.08% compared to other prepared cream. Comparison of the inhibitory activity of the formulations demonstrated that the rank order was HC3.2 > HC3.3 > HC1.2 > HC1.3 > HC3.1 > HC1.1 > HC2.3 > HC2.2 > HC2.1. It has been observed from the result that the formulations of antityrosinase activity were not concentrate dependent. This finding suggests that decrease in antityrosinase activity of HC1 and HC3 might be considering that the incompatibility of the higher extract content with the base of cream. The HC3 produce the maximum inhibitory effects on tyrosinase activity might be due to higher level of polyphenol and flavonoids present in extracts. PMID:24783796

  10. Benzenesulfonamides incorporating bulky aromatic/heterocyclic tails with potent carbonic anhydrase inhibitory activity.

    Bozdag, Murat; Alafeefy, Ahmed M; Vullo, Daniela; Carta, Fabrizio; Dedeoglu, Nurcan; Al-Tamimi, Abdul-Malek S; Al-Jaber, Nabila A; Scozzafava, Andrea; Supuran, Claudiu T

    2015-12-15

    Three series of sulfonamides incorporating long, bulky tails were obtained by applying synthetic strategies in which substituted anthranilic acids, quinazolines and aromatic sulfonamides have been used as starting materials. They incorporate long, bulky diamide-, 4-oxoquinazoline-3-yl- or quinazoline-4-yl moieties in their molecules, and were investigated for the inhibition of four physiologically relevant carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic human (h) hCA I and II, as well as the transmembrane hCA IX and XII. Most of the new sulfonamides showed excellent inhibitory effects against the four isoforms, with KIs of 7.6-322nM against hCA I, of 0.06-85.4nM against hCA II; of 6.7-152nM against hCA IX and of 0.49-237nM against hCA XII; respectively. However no relevant isoform-selective behavior has been observed for any of them, although hCA II and XII, isoforms involved in glaucoma-genesis were the most inhibited ones. The structure-activity relationship for inhibiting the four CAs with these derivatives is discussed in detail. PMID:26639945

  11. Anoctamin Calcium-Activated Chloride Channels May Modulate Inhibitory Transmission in the Cerebellar Cortex.

    Weiping Zhang

    Full Text Available Calcium-activated chloride channels of the anoctamin (alias TMEM16 protein family fulfill critical functions in epithelial fluid transport, smooth muscle contraction and sensory signal processing. Little is known, however, about their contribution to information processing in the central nervous system. Here we examined the recent finding that a calcium-dependent chloride conductance impacts on GABAergic synaptic inhibition in Purkinje cells of the cerebellum. We asked whether anoctamin channels may underlie this chloride conductance. We identified two anoctamin channel proteins, ANO1 and ANO2, in the cerebellar cortex. ANO1 was expressed in inhibitory interneurons of the molecular layer and the granule cell layer. Both channels were expressed in Purkinje cells but, while ANO1 appeared to be retained in the cell body, ANO2 was targeted to the dendritic tree. Functional studies confirmed that ANO2 was involved in a calcium-dependent mode of ionic plasticity that reduces the efficacy of GABAergic synapses. ANO2 channels attenuated GABAergic transmission by increasing the postsynaptic chloride concentration, hence reducing the driving force for chloride influx. Our data suggest that ANO2 channels are involved in a Ca2+-dependent regulation of synaptic weight in GABAergic inhibition. Thus, in balance with the chloride extrusion mechanism via the co-transporter KCC2, ANO2 appears to regulate ionic plasticity in the cerebellum.

  12. Sulforaphane Analogues with Heterocyclic Moieties: Syntheses and Inhibitory Activities against Cancer Cell Lines

    Ye-Hui Shi

    2016-04-01

    Full Text Available Recent studies have shown that sulforaphane (SFN selectively inhibits the growth of ALDH+ breast cancer stem-like cells.Herein, a series of SFN analogues were synthesized and evaluated against breast cancer cell lines MCF-7 and SUM-159, and the leukemia stem cell-like cell line KG-1a. These SFN analogues were characterized by the replacement of the methyl group with heterocyclic moieties, and the replacement of the sulfoxide group with sulfide or sulfone. A growth inhibitory assay indicated that the tetrazole analogs 3d, 8d and 9d were significantly more potent than SFN against the three cancer cell lines. Compound 14c, the water soluble derivative of tetrazole sulfide 3d, demonstrated higher potency against KG-1a cell line than 3d. SFN, 3d and 14c significantly induced the activation of caspase-3, and reduced the ALDH+ subpopulation in the SUM159 cell line, while the marketed drug doxrubicin(DOX increased the ALDH+ subpopulation.

  13. Sulforaphane Analogues with Heterocyclic Moieties: Syntheses and Inhibitory Activities against Cancer Cell Lines.

    Shi, Ye-Hui; Dai, Dong-Fang; Li, Jing; Dong, Yan-Wei; Jiang, Yin; Li, Huan-Gong; Gao, Yuan; Chong, Chuan-Ke; Li, Hui-Ying; Chu, Xiao-Qian; Yang, Cheng; Zhang, Quan; Tong, Zhong-Sheng; Bai, Cui-Gai; Chen, Yue

    2016-01-01

    Recent studies have shown that sulforaphane (SFN) selectively inhibits the growth of ALDH⁺ breast cancer stem-like cells.Herein, a series of SFN analogues were synthesized and evaluated against breast cancer cell lines MCF-7 and SUM-159, and the leukemia stem cell-like cell line KG-1a. These SFN analogues were characterized by the replacement of the methyl group with heterocyclic moieties, and the replacement of the sulfoxide group with sulfide or sulfone. A growth inhibitory assay indicated that the tetrazole analogs 3d, 8d and 9d were significantly more potent than SFN against the three cancer cell lines. Compound 14c, the water soluble derivative of tetrazole sulfide 3d, demonstrated higher potency against KG-1a cell line than 3d. SFN, 3d and 14c significantly induced the activation of caspase-3, and reduced the ALDH⁺ subpopulation in the SUM159 cell line, while the marketed drug doxrubicin(DOX) increased the ALDH⁺ subpopulation. PMID:27110751

  14. New constituents with iNOS inhibitory activity from mycelium of Antrodia camphorata.

    Yang, Sien-Sing; Wang, Guei-Jane; Wang, Shiang-Yi; Lin, Yu-Ying; Kuo, Yueh-Hsiung; Lee, Tzong-Huei

    2009-04-01

    In continuing our investigation on the bioactive constituents of mycelium of Antrodia camphorata, antroquinonol B (1), 4-acetyl-antroquinonol B (2), 2,3-(methylenedioxy)-6-methylbenzene-1,4-diol (3) and 2,4-dimethoxy-6-methylbenzene-1,3-diol (4) along with antrodin D (5) were isolated by the guidance of an inducible nitric oxide synthase (iNOS) inhibitory assay and identified on the basis of their spectroscopic analysis. The effect of these compounds on the inhibition of NO production in lipopolysaccharide (LPS)-activated murine macrophages was further evaluated. Compounds 4 and 5 significantly inhibited NO production without any cytotoxicity, the IC(50) values being 32.2 +/- 0.1 and 26.3 +/- 1.6 microg/mL, respectively. Compounds 1 and 2 possessed greater effects on NO inhibition, with IC(50) values of 16.2 +/- 0.8 and 14.7 +/- 2.8 microg/mL, respectively, but displayed cytotoxicity at considerably higher concentrations. Compound 3 showed the lowest percent cell viability of 45.5 +/- 1.8 % as observed in treated cells at a concentration of 16.8 microg/mL. PMID:19189245

  15. Inhibitory activities against rice pathogens of 8-hydroxy-2,4,6-octatriynamide from Agrocybe sp.

    Zheng, Yongbiao; Xu, Xiaoping; Wu, Yabin

    2016-03-01

    8-Hydroxy-2,4,6-octatriynamide, a natural polyacetylene with inhibitory activities against rice pathogens, was isolated from the liquid fermentation broth of strain Agrocybe sp. YB2005 during screening for new natural chemical agents to control rice pathogens. 8-hydroxy-2,4,6-octatriynamide was purified by consecutive chromatography over a Cl8 reversed phase silica gel, sephadex LH-20 and silica gel. The chemical structure of 8-hydroxy-2,4,6-octatriynamide was elucidated through spectroscopic analyses, including 1D- and 2D-NMR, ESI mass spectrometry and X-ray single crystal diffraction. Bioassays showed that 8-hydroxy-2,4,6-octatriynamide could significantly inhibit growth of Xanthomonas oryzae with an MIC of 53.1 μM in a 96-well plate and the growth of Rhizoctonia solani at 1.02 mM in a 24-well plate. When rice leaves were inoculated with Magnaporthe grisea and cultured in artificial nutrition liquid containing 0.34 mM 8-hydroxy-2,4,6-octatriynamide, no rice blast was observed. The present study implied that 8-hydroxy-2,4,6-octatriynamide could be a candidate agent against rice pathogens. PMID:26861586

  16. Inhibitory potential of some Romanian medicinal plants against enzymes linked to neurodegenerative diseases and their antioxidant activity

    Gabriela Paun

    2015-01-01

    Full Text Available Context: Eryngium planum, Geum urbanum and Cnicus benedictus plants are an endemic botanical from the Romanian used in folk medicine. Objective: The extracts from three Romanian medicinal plants were investigated for their possible neuroprotective potential. Materials and Methods: Within this study, in vitro neuroprotective activity of the extracts of E. planum, G. urbanum, and C. benedictus plants were investigated via inhibition of acetylcholinesterase (AChE and tyrosinase (TYR. Total content of phenolics, flavonoids, and proanthocyanidins, high-performance liquid chromatography profile of the main phenolic compounds and antioxidant activity were also determined. Results: Among the tested extracts, the best inhibition of AChE (88.76 ± 5.2% and TYR (88.5 ± 5.2% was caused by C. benedictus ethanol (EtOH extract. The G. urbanum extracts exerted remarkable scavenging effect against 2,2-diphenyl-1-picrylhydrazyl (IC 50 , 7.8 ± 0.5 μg/mL aqueous extract, and IC 50 , 1.3 ± 0.1 μg/mL EtOH extract, respectively and reducing power, whereas the EtOH extract of C. benedictus showed high scavenging activity (IC 50 , 0.609 ± 0.04 mg/mL, also. Conclusion: According to our knowledge, this is the first study that demonstrates in vitro neuroprotective effects of E. planum, G. urbanum and C. benedictus.

  17. Preparation of bioactive peptides with high angiotensin converting enzyme inhibitory activity from winged bean [Psophocarpus tetragonolobus (L.) DC.] seed.

    Wan Mohtar, Wan Abd Al-Qadr Imad; Hamid, Azizah Abdul; Abd-Aziz, Suraini; Muhamad, Sharifah Kharidah Syed; Saari, Nazamid

    2014-12-01

    Winged bean [Psophocarpus tetragonolobus (L.) DC.] seed is a potential underexploited source of vegetable protein due to its high protein content. In the present work, undefatted and defatted winged bean seed hydrolysates, designated as UWBSH and DWBSH, respectively were produced separately by four proteolytic enzymes namely Flavourzyme, Alcalase, Bromelain, and Papain using pH-stat method in a batch reactor. Enzymatic hydrolysis was carried out over a period of 0.5 to 5 h. UWBSH and DWBSH produced were tested for their ACE inhibitory activity in relation to the hydrolysis time and degree of hydrolysis (DH). Maximum ACE inhibitory activity, both for UWBSH and DWBSH, were observed during 3 to 5 h of hydrolysis. Both, UWBSH (DH 91.84 %), and DWSBH (DH 18.72 %), produced by Papain at 5 h hydrolysis, exhibited exceptionally high ACE inhibitory activity with IC50 value 0.064 and 0.249 mg mL(-1), respectively. Besides, papain-produced UWBSH and DWBSH were further fractionated into three fractions based on molecular weight (UWBSH-I, <10 kDa; UWBSH-II, <5 kDa; UWBSH-III, <2 kDa) and (DWBSH-I, <10 kDa; DWBSH-II, <5 kDa; DWBSH-III, <2 kDa). UWBSH-III revealed the highest ACE inhibitory activity (IC50 0.003 mg mL(-1)) compared with DWBSH-III (IC50 0.130 mg mL(-1)). The results of the present investigation revealed that winged bean seed hydrolysates can be explored as a potential source of ACE inhibitory peptides suggesting their uses for physiological benefits as well as for other functional food applications. PMID:25477632

  18. Effects of Sequential Applications of Bassa 50EC (Fenobucarb) and Vitashield 40EC (Chlorpyrifos ethyl) on Acetylcholinesterase Activity in Climbing Perch (Anabas testudineus) Cultured in Rice Fields in the Mekong Delta, Vietnam.

    Tam, Nguyen Thanh; Berg, Håkan; Laureus, Jenny; Cong, Nguyen Van; Tedengren, Michael

    2016-07-01

    This study assesses the effects of sequential applications of the insecticides Bassa 50EC (fenobucarb-F) and Vitashield 40EC (chlorpyrifos ethyl-CPF), sprayed at concentrations used by rice farmers in the Mekong Delta, on the brain acetylcholinesterase (AChE) in climbing perch fingerlings. After spraying the pesticides on the rice fields, the water concentrations of both insecticides decreased below the detection levels within 3 days. The sequential applications caused significant inhibition on the brain AChE activity in the exposed fish. The inhibition by F was quicker, but less prolonged, than for CPF. The inhibition levels caused by the sequential applications were lower than those caused by only CPF and by a mixture of CPF and F. The results indicate that sequential applications of pesticides could have a negative impact on aquatic organisms and fish yields, with implication for the aquatic biodiversity, local people's livelihood and the aquaculture industry in the Mekong Delta. PMID:27075585

  19. Prediction of inhibitory activity of epidermal growth factor receptor inhibitors using grid search-projection pursuit regression method.

    Hongying Du

    Full Text Available The epidermal growth factor receptor (EGFR protein tyrosine kinase (PTK is an important protein target for anti-tumor drug discovery. To identify potential EGFR inhibitors, we conducted a quantitative structure-activity relationship (QSAR study on the inhibitory activity of a series of quinazoline derivatives against EGFR tyrosine kinase. Two 2D-QSAR models were developed based on the best multi-linear regression (BMLR and grid-search assisted projection pursuit regression (GS-PPR methods. The results demonstrate that the inhibitory activity of quinazoline derivatives is strongly correlated with their polarizability, activation energy, mass distribution, connectivity, and branching information. Although the present investigation focused on EGFR, the approach provides a general avenue in the structure-based drug development of different protein receptor inhibitors.

  20. Bioassay- and liquid chromatography/mass spectrometry-guided acetylcholinesterase inhibitors from Picriafel-terrae

    Lu Wen

    2013-01-01

    Full Text Available Background: Picria fel-terrae is a traditional Chinese medicine. Materials and Methods: A new approach to the search for acetylcholinesterase (AChE inhibitors from Picria fel-terrae is presented. Results: Bioassay- and LC-MS-guided fractionation of the ethyl acetate extract was from traditional Chinese medicine P.fel-terrae. Following primary extraction, the ethyl acetate extracts fraction of P.fel-terrae showed strong AChE inhibitory activities. So the sample was separated using highperformance liquid chromatography (HPLC. The effluent was split towards two identical 96-well fraction collectors, and the presence of the biologically interesting portion and chromatographic fractions could be readily detected by analyzing selected ion chromatograms through an electrophoresis-electrospray ionization mass spectrometry (ESIMS system for accurate mass measurement. One 96-well plate was used for a bioassay (AChE-inhibitory assay and detected the bioactivity and position of the relevant peak in the chromatogram. The positive well in the second 96-well plate was used for identification by LC-(+ ESIMS. Conclusion: As abovementioned, the AChE inhibitory constituents from P.fel-terrae by LC-bioassay-ESIMS were rapid identified. Liquid chromatography/ mass spectrometry (LC-MS screening detected the presence of six active compounds, identified as picfeltarraenin IA (1, picfeltarraenin IB (2, picfeltarraenin IV (3, picfeltarraenin X (4, picfeltarraenin XI (5, and one unknown compound. The structures were further determined by 13C NMR. The six compounds expressed stronger AChE inhibition than the known AChE inhibitorTacrine. Above all, the value of this LC-bioassay-ESIMS methodology is highlighted by the finding and structure elucidation of the active constituents from many other structural families of natural products.

  1. Inhibitory effects of kiwifruit extract on human platelet aggregation and plasma angiotensin-converting enzyme activity.

    Dizdarevic, Lili L; Biswas, Dipankar; Uddin, M D Main; Jørgenesen, Aud; Falch, Eva; Bastani, Nasser E; Duttaroy, Asim K

    2014-01-01

    Previous human studies suggest that supplementation with kiwifruits lowers several cardiovascular risk factors such as platelet hyperactivity, blood pressure and plasma lipids. The cardiovascular health benefit of fruit and vegetables is usually attributed to the complex mixture of phytochemicals therein; however, kiwifruit's cardioprotective factors are not well studied. In this study, we investigated the effects of kiwifruit extract on human blood platelet aggregation and plasma angiotensin-converting enzyme (ACE) activity. A sugar-free, heat-stable aqueous extract with molecular mass less than 1000 Da was prepared from kiwifruits. Typically, 100 g kiwifruits produced 66.3 ± 5.8 mg (1.2 ± 0.1 mg CE) of sugar-free kiwifruit extract (KFE). KFE inhibited both human platelet aggregation and plasma ACE activity in a dose-dependent manner. KFE inhibited platelet aggregation in response to ADP, collagen and arachidonic acid, and inhibitory action was mediated in part by reducing TxA2 synthesis. The IC50 for ADP-induced platelet aggregation was 1.6 ± 0.2 mg/ml (29.0 ± 3.0 μg CE/ml), whereas IC50 for serum ACE was 0.6 ± 0.1 mg/ml (11.0 ± 1.2 μg CE/ml). Consuming 500 mg of KFE (9.0 mg CE) in 10 g margarine inhibited ex vivo platelet aggregation by 12.7%, 2 h after consumption by healthy volunteers (n = 9). All these data indicate that kiwifruit contains very potent antiplatelet and anti-ACE components. Consuming kiwifruits might be beneficial as both preventive and therapeutic regime in cardiovascular disease. PMID:24219176

  2. Memory retrieval of inhibitory avoidance requires histamine H1 receptor activation in the hippocampus.

    Fabbri, Roberta; Furini, Cristiane Regina Guerino; Passani, Maria Beatrice; Provensi, Gustavo; Baldi, Elisabetta; Bucherelli, Corrado; Izquierdo, Ivan; de Carvalho Myskiw, Jociane; Blandina, Patrizio

    2016-05-10

    Retrieval represents a dynamic process that may require neuromodulatory signaling. Here, we report that the integrity of the brain histaminergic system is necessary for retrieval of inhibitory avoidance (IA) memory, because rats depleted of histamine through lateral ventricle injections of α-fluoromethylhistidine (a-FMHis), a suicide inhibitor of histidine decarboxylase, displayed impaired IA memory when tested 2 d after training. a-FMHis was administered 24 h after training, when IA memory trace was already formed. Infusion of histamine in hippocampal CA1 of brain histamine-depleted rats (hence, amnesic) 10 min before the retention test restored IA memory but was ineffective when given in the basolateral amygdala (BLA) or the ventral medial prefrontal cortex (vmPFC). Intra-CA1 injections of selective H1 and H2 receptor agonists showed that histamine exerted its effect by activating the H1 receptor. Noteworthy, the H1 receptor antagonist pyrilamine disrupted IA memory retrieval in rats, thus strongly supporting an active involvement of endogenous histamine; 90 min after the retention test, c-Fos-positive neurons were significantly fewer in the CA1s of a-FMHis-treated rats that displayed amnesia compared with in the control group. We also found reduced levels of phosphorylated cAMP-responsive element binding protein (pCREB) in the CA1s of a-FMHis-treated animals compared with in controls. Increases in pCREB levels are associated with retrieval of associated memories. Targeting the histaminergic system may modify the retrieval of emotional memory; hence, histaminergic ligands might reduce dysfunctional aversive memories and improve the efficacy of exposure psychotherapies. PMID:27118833

  3. Synthesis of ∆3-2-Hydroxybakuchiol Analogues and Their Growth Inhibitory Activity against Rat UMR106 Cells

    Qun Zhao

    2014-02-01

    Full Text Available A series of ∆3-2-hydroxybakuchiol analogues have been synthesized and tested for their growth inhibitory activity against rat UMR106 cells by using the MTT method. Some of them exhibit enhanced activities compared with the natural product, and the preliminary SAR profile shows that the chain tail on the natural product could be subtly modified to enhance the activity and the aromatic moiety or the terminal olefin on the main chain can also be modified without any evident loss of activity. The stereo-configuration of the quaternary chiral center has an important influence on the activity.

  4. Blocking macrophage migration inhibitory factor activity alleviates mouse acute otitis media in vivo.

    Zhang, Jin; Xu, Min; Zheng, Qingyin; Zhang, Yan; Ma, Weijun; Zhang, Zhaoqiang

    2014-11-01

    This study was to investigate the role of macrophage migration inhibitory factor (MIF) in mouse acute otitis media (AOM), we hypothesize that blocking MIF activity will relieve mouse AOM. A mouse AOM model was constructed by injecting lipopolysaccharide (LPS) into the middle ear of C57BL/6 mice through the tympanic membrane (TM). MIF levels were measured by real-time PCR (RT-PCR) and ELISA after LPS application. Normal or AOM mice were given PBS or ISO-1 (MIF antagonist) every day for 10 days and the hearing levels were determined by measuring auditory brainstem response (ABR) threshold. After the ABR test finished, H&E staining was conducted and the inflammation was also measured by detecting interleukin (IL)-1β, tumor necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) levels with RT-PCR and ELISA. TLR-4 expression was determined by western blotting and NF-κB activation was determined by electrophoretic mobility shift assays. Compared with the normal control, MIF levels in the middle ear of LPS-induced AOM mice were significant increased. The ABR results showed that mean ABR thresholds in ISO-1 treated AOM mice were significantly reduced compared with PBS treated AOM mice since day 7, indicating that ISO-1 treatment potentially improved the hearing levels of AOM mice. H&E staining showed that ISO-1 treatment could reduce the mucosal thickness of AOM mice. In ISO-1 treated mice, TLR-4 expression and levels of IL-1β, TNF-α and VEGF were significantly lower compared with PBS treated AOM mice. ISO-1 treatment also significantly inhibited NF-κB activation in AOM mice compared with PBS treated AOM mice. These results suggested that blocking the activity of MIF by ISO-1 could reduce the inflammation in AOM mice in which process TLR-4 and NF-κB were involved. The reduction in MIF activity is conducive to alleviate mouse AOM, which may serve as a potential therapeutic target for the treatment of AOM. PMID:25108100

  5. Correlation of cognitive function with acetylcholinesterase activity and P300 event-related potential of patients with type 2 diabetes mellitus

    Suguo Yu; Yingxue Wang; Jihua Sun; Xuewen Han

    2006-01-01

    BACKGROUND: At present, central cholinergic neuron system is regarded the most major structural basis of cognitive function. Changes in structure of cholinergic neuron system of brain and receptor expression after brain injury can cause cognitive impairment.OBJECTIVE: To comparatively observe the intelligence quotient (IQ), latent period and wave amplitude of P300 event-related potential and the difference of activity of acetylcholinesterase (AChE) in blood and cerebrospinal fluid between patients with type 2 diabetes mellitus and with non-diabetes mellitus, and analyze the correlation of IQ of cognitive impairment patients with diabetes mellitus with AChE activity, latent period and wave amplitude of P300 event-related potential in cerebrospinal fluid.DESIGN: Correlation analysis of contrast observation.SETTING: Department of Endocrinology, Affiliated Hospital of Binzhou Medical College.PARTICIPANTS: Totally 32 patients with type 2 diabetes mellitus who received the treatment in the Department of Endocrinology, Affiliated Hospital of Binzhou Medical College between April 2004 and April 2005 were recruited, serving as diabetes mellitus group. They, including 19 male and 13 female, aged 49 to 73 years, with disease course of 4 to 11 years, all met the diagnostic criteria of diabetes mellitus revised by World Health Organization in 1999. Another 30 patients with non-diabetes mellitus who homeochronously underwent lumbar anesthesia in the Department of Surgery and Department of Gynecology were recruited, serving as non-diabetes mellitus group. The 30 patients included 18 male and 12 female,and their age ranged from 46 to 71 years. Informed consents of detected items were obtained from the involved patients.METHODS: ① Evaluation,on IQ: The IQ of involved subjects was evaluated with Chinese Version of the Wechsler Adult Intelligence Scale revised by Gong Yao-xian (WAIS-RC). WAIS-RC included 6 verbal subscales and 5 performance subscales. The test scores of the 11

  6. Extracts from Amazonian plants have inhibitory activity against tyrosinase: an in vitro evaluation

    Daclé Juliani Macrini

    2009-12-01

    Full Text Available Dermatological disorders related to pigmentation result in tenuous hyper or hypopigmentation Cosmetic and pharmaceutical products containing depigmenting substances are used in the treatment of patients who have high pigmentation disorders, such as melasma or chloasma, post-inflammatory hyperpigmentation, senile lentigo and ephelides. Skin lightening agents are not yet totally effective or safe and therefore intensive research for the discovery of new agents is continuous. Enzyme inhibitors involved in melanogenesis, such as tyrosinase, have been discovered in Asian countries, including those isolated from plant extracts. The Brazilian flora has the highest species diversity in the world, and the chemical, pharmacological and cosmetic potential for the discovery of new skin whitening agents is in proportion with this biodiversity. For these reasons, 25 aqueous and 24 organic extracts obtained from 19 plants native to the Amazon rain forest and to the Atlantic forest, belonging to 11 different families, were evaluated as tyrosinase inhibitors. Nine out of 49 extracts showed inhibitory activity in the screening process. The 50% inhibitory activity (IA50 was calculated, revealing that the most active extracts were the organic extracts from the leaves and stem of Ruprechtia sp. (IA50 33.76 mg.mL-1 and the organic extract from the aerial organs of Rapanea parviflora (IA50 64.19 mg.mL-1.Problemas dermatológicos relacionados com a pigmentação resultam em hiperpigmentações ou hipopigmentação cutâneas. Produtos cosméticos e farmacêuticos com atividade despigmentante são utilizados para o tratamento de pacientes que apresentam distúrbios de hiperpigmentação, tais como melasma ou cloasma, hiperpigmentação pós-inflamatória, lentigem senil e efélides. Os despigmentantes atualmente utilizados não são totalmente eficazes ou seguros, razão pela qual há intensa pesquisa, principalmente em países asiáticos, com a finalidade de se obter

  7. In vitro xanthine oxidase inhibitory activity of methanol extracts of Erythrina indica Lam. leaves and stem bark

    Kandhasamy Sowndhararajan; Jince Mary Joseph; Dharmar Rajendrakumaran

    2012-01-01

    Objective: To determine the total phenolic content and in vitro xanthine oxidase inhibitory activity of methanol extracts of leaves and stem bark of Erythrina indica. Methods: Folin-ciocalteu method was used to determine the total phenolic content. Xanthine oxidase inhibitory activity was assayed spectrophotometrically and the degree of enzyme inhibition was determined by measuring the increase in absorbance at 295nm associated with uric acid formation. Results:The methanol extract of stem bark of E. indica contains higher level of total phenolic content (412.8 mg GAE/g extract) and also exhibited higher xanthine oxidase inhibition activity (IC50 52.75μg/mL) than the leaves. Conclusions: It could be concluded that the stem bark of E. indica was highly effective in xanthine oxidase inhibition and might be used for the gout related disorders.

  8. A Support Vector Machine Classification Model for Benzo[c]phenathridine Analogues with Topoisomerase-I Inhibitory Activity

    Thanh-Dao Tran

    2012-04-01

    Full Text Available Benzo[c]phenanthridine (BCP derivatives were identified as topoisomerase I (TOP-I targeting agents with pronounced antitumor activity. In this study, a support vector machine model was performed on a series of 73 analogues to classify BCP derivatives according to TOP-I inhibitory activity. The best SVM model with total accuracy of 93% for training set was achieved using a set of 7 descriptors identified from a large set via a random forest algorithm. Overall accuracy of up to 87% and a Matthews coefficient correlation (MCC of 0.71 were obtained after this SVM classifier was validated internally by a test set of 15 compounds. For two external test sets, 89% and 80% BCP compounds, respectively, were correctly predicted. The results indicated that our SVM model could be used as the filter for designing new BCP compounds with higher TOP-I inhibitory activity.

  9. Angiotensin-I-Converting Enzyme Inhibitory and Antioxidant Activities of Protein Hydrolysate from Muscle of Barbel (Barbus callensis

    Assaad Sila

    2013-01-01

    Full Text Available The present study investigated angiotensin-I-converting enzyme (ACE inhibitory and antioxidant activities of barbel muscle protein hydrolysate prepared with Alcalase. The barbel muscle protein hydrolysate displayed a high ACE inhibitory activity (CI50=0.92 mg/mL. The antioxidant activities of protein hydrolysate at different concentrations were evaluated using various in vitro antioxidant assays, including 1,1-diphenyl-2-picrylhydrazyl (DPPH radical method and reducing power assay. The barbel muscle protein hydrolysate exhibited an important radical scavenging effect and reducing power. These results obtained by in vitro systems obviously established the antioxidant potency of barbel hydrolysate to donate electron or hydrogen atom to reduce the free radical. Furthermore, these bioactive substances can be exploited into functional foods or used as source of nutraceuticals.

  10. Isolation, modification, and aldose reductase inhibitory activity of rosmarinic acid derivatives from the roots of Salvia grandifolia.

    Kang, Jie; Tang, Yanbo; Liu, Quan; Guo, Nan; Zhang, Jian; Xiao, Zhiyan; Chen, Ruoyun; Shen, Zhufang

    2016-07-01

    To find aldose reductase inhibitors, two previously unreported compounds, grandifolias H and I, and five known compounds, including rosmarinic acid and rosmarinic acid derivatives, were isolated from the roots of Salvia grandifolia. A series of rosmarinic acid derivatives was obtained from rosmarinic acid using simple synthetic methods. The aldose reductase inhibitory activity of the isolated and synthesized compounds was assessed. Seven of the tested compounds showed moderate aldose reductase inhibition (IC50=0.06-0.30μM). The structure-activity relationship of aldose reductase inhibitory activity of rosmarinic acid derivatives was discussed for the first time. This study provided useful information that will facilitate the development of aldose reductase inhibitors. PMID:27233987

  11. Description of two Enterococcus strains isolated from traditional Peruvian artisanal-produced cheeses with a bacteriocin-like inhibitory activity

    Aguilar Galvez A.

    2009-01-01

    Full Text Available The aim of this work was to isolate and to characterize strains of lactic acid bacteria (LAB with bacteriocin-like inhibitory activity from 27 traditional cheeses artisanal-produced obtained from different Peruvian regions. Twenty Gram+ and catalasenegative strains among 2,277 isolates exhibited bacteriocin-like inhibitory activity against Listeria monocytogenes CWBIB2232 as target strain. No change in inhibitory activity was observed after organic acid neutralization and treatment with catalase of the cell-free supernatant (CFS. The proteinic nature of the antimicrobial activity was confirmed for the twenty LAB strains by proteolytic digestion of the CFS. Two strains, CWBI-B1431 and CWBI-B1430, with the best antimicrobial activity were selected for further researches. These strains were taxonomically identified by phenotypic and genotypic analyses as Enterococcus mundtii (CWBI-B1431 and Enterococcus faecium (CWBI-B1430. The two strains were sensitive to vancomycin (MIC 2 μg.ml-1 and showed absence of haemolysis.

  12. Limonoids from Azadirachta indica var. siamensis extracts and their cytotoxic and melanogenesis-inhibitory activities.

    Manosroi, Aranya; Kitdamrongtham, Worapong; Ishii, Kenta; Shinozaki, Takuro; Tachi, Yosuke; Takagi, Mio; Ebina, Kodai; Zhang, Jie; Manosroi, Jiradej; Akihisa, Rima; Akihisa, Toshihiro

    2014-04-01

    Six new limonoids, 7-benzoyl-17-epinimbocinol (5), 3-acetyl-7-tigloylnimbidinin (8), 1-isovaleroyl-1-detigloylsalanninolide (15), 2,3-dihydro-3α-methoxynimbolide (16), deacetyl-20,21-epoxy-20,22-dihydro-21-deoxyisonimbinolide (26), and deacetyl-20,21,22,23-tetrahydro-20,22-dihydroxy-21,23-dimethoxynimbin (27), along with 28 known limonoids, 1-4, 6, 7, 9-14, 17-25, and 28-34, and two known flavonoids, 35 and 36, have been isolated from the extracts of bark, leaves, roots, and seeds of Azadirachta indica A. Juss. var. siamensis Valeton (Siamese neem tree; Meliaceae). The structures of the new compounds were elucidated on the basis of extensive spectroscopic analysis and comparison with literature data. All of these compounds were evaluated for their cytotoxic activities against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3) cancer cell lines. Eleven compounds, 1, 2, 4-7, 13, 16, 17, 29, and 30, exhibited potent cytotoxicities against one or more cell lines with IC50 values in the range of 0.1-9.3 μM. Compound 16 induced apoptotic cell death in AZ521 cells upon evaluation of the apoptosis-inducing activity by flow cytometric analysis. Western blot analysis on AZ521 cells revealed that compound 16 activated caspases-3, -8, and -9, while increasing the ratio of Bax/Bcl-2. This suggested that 16 induced apoptosis via both mitochondrial and death receptor pathways in AZ521. In addition, upon evaluation of all compounds against the melanogenesis in B16 melanoma cells induced with α-melanocyte-stimulating hormone (α-MSH), 20 limonoids, i.e., 1-3, 6, 9-11, 18, 19, 21-29, 32, and 34, and two flavonoids, 35 and 36, exhibited melanogenesis-inhibitory activities, with no, or almost no, toxicities to the cells at lower and/or higher concentrations, which were more potent than the reference arbutin, a known melanogenesis inhibitor. Western blot analysis showed that nimbin (18) reduced the protein levels of microphtalmia-associated transcription factor

  13. UV-B Radiation Induces Macrophage Migration Inhibitory Factor–Mediated Melanogenesis through Activation of Protease-Activated Receptor-2 and Stem Cell Factor in Keratinocytes

    Enomoto, Akiko; Yoshihisa, Yoko; Yamakoshi, Takako; Ur Rehman, Mati; Norisugi, Osamu; HARA Hiroshi; Matsunaga, Kenji; Makino, Teruhiko; Nishihira, Jun; Shimizu, Tadamichi

    2011-01-01

    UV radiation indirectly regulates melanogenesis in melanocytes through a paracrine regulatory mechanism involving keratinocytes. Protease-activated receptor (PAR)-2 activation induces melanosome transfer by increasing phagocytosis of melanosomes by keratinocytes. This study demonstrated that macrophage migration inhibitory factor (MIF) stimulated PAR-2 expression in human keratinocytes. In addition, we showed that MIF stimulated stem cell factor (SCF) release in keratinocytes; however, MIF ha...

  14. Inhibitory effects of SKF96365 on the activities of K(+) channels in mouse small intestinal smooth muscle cells.

    Tanahashi, Yasuyuki; Wang, Ban; Murakami, Yuri; Unno, Toshihiro; Matsuyama, Hayato; Nagano, Hiroshi; Komori, Seiichi

    2016-03-01

    In order to investigate the effects of SKF96365 (SKF), which is a non-selective cationic channel blocker, on K(+) channel currents, we recorded currents through ATP sensitive K(+) (IKATP), voltage-gated K(+) (IKv) and Ca(2+) activated K(+) channels (IBK) in the absence and presence of SKF in single small intestinal myocytes of mice with patch-clamp techniques. SKF (10 µM) reversibly abolished IKATP that was induced by cromakalim (10 µM), which is a selective ATP sensitive K(+) channel opener. These inhibitory effects were induced in a concentration-dependent and voltage-independent manner. The 50% inhibitory concentration (IC50) was 0.85 µM, which was obviously lower than that reported for the muscarinic cationic current. In addition, SKF (1 µM ≈ the IC50 value in IKATP suppression) reversibly inhibited the IKv that was induced by repetitive depolarizing pulses from -80 to 20 mV. However, the extent of the inhibitory effects was only ~30%. In contrast, SKF (1 µM) had no significant effects on spontaneous transient IBK and caffeine-induced IBK. These results indicated that SKF inhibited ATP sensitive K(+) channels and voltage-gated K(+) channels, with the ATP sensitive K(+) channels being more sensitive than the voltage-gated K(+) channels. These inhibitory effects on K(+) channels should be considered when SKF is used as a cationic channel blocker. PMID:26498720

  15. Merkel cell polyomavirus large T antigen has growth-promoting and inhibitory activities.

    Cheng, Jingwei; Rozenblatt-Rosen, Orit; Paulson, Kelly G; Nghiem, Paul; DeCaprio, James A

    2013-06-01

    Merkel cell carcinoma (MCC) is a rare and aggressive form of skin cancer. In at least 80% of all MCC, Merkel cell polyomavirus (MCPyV) DNA has undergone clonal integration into the host cell genome, and most tumors express the MCPyV large and small T antigens. In all cases of MCC reported to date, the integrated MCPyV genome has undergone mutations in the large T antigen. These mutations result in expression of a truncated large T antigen that retains the Rb binding or LXCXE motif but deletes the DNA binding and helicase domains. However, the transforming functions of full-length and truncated MCPyV large T antigen are unknown. We compared the transforming activities of full-length, truncated, and alternatively spliced 57kT forms of MCPyV large T antigen. MCPyV large T antigen could bind to Rb but was unable to bind to p53. Furthermore, MCPyV-truncated large T antigen was more effective than full-length and 57kT large T antigen in promoting the growth of human and mouse fibroblasts. In contrast, expression of the MCPyV large T antigen C-terminal 100 residues could inhibit the growth of several different cell types. These data imply that the deletion of the C terminus of MCPyV large T antigen found in MCC serves not only to disrupt viral replication but also results in the loss of a distinct growth-inhibitory function intrinsic to this region. PMID:23514892

  16. Biological activity of a genetically modified BMP-2 variant with inhibitory activity

    Kübler Alexander C

    2009-02-01

    Full Text Available Abstract Background Alterations of the binding epitopes of bone morphogenetic protein-2 (BMP-2 lead to a modified interaction with the ectodomains of BMP receptors. In the present study the biological effect of a BMP-2 double mutant with antagonistic activity was evaluated in vivo. Methods Equine-derived collagenous carriers were loaded with recombinant human BMP-2 (rhBMP-2 in a well-known dose to provide an osteoinductive stimulus. The study was performed in a split animal design: carriers only coupled with rhBMP-2 (control were implanted into prepared cavities of lower limb muscle of rats, specimens coupled with rhBMP-2 as well as BMP-2 double mutant were placed into the opposite limb in the same way. After 28 days the carriers were explanted, measured radiographically and characterized histologically. Results As expected, the BMP-2 loaded implants showed a typical heterotopic bone formation. The specimens coupled with both proteins showed a significant decreased bone formation in a dose dependent manner. Conclusion The antagonistic effect of a specific BMP-2 double mutant could be demonstrated in vivo. The dose dependent influence on heterotopic bone formation by preventing rhBMP-2 induced osteoinduction suggests a competitive receptor antagonism.

  17. Acetylcholinesterase as a Biomarker in Environmental and Occupational Medicine: New Insights and Future Perspectives

    Trifone Schettino; Maria Elena Giordano; Antonio Calisi; Maria Giulia Lionetto; Roberto Caricato

    2013-01-01

    Acetylcholinesterase (AChE) is a key enzyme in the nervous system. It terminates nerve impulses by catalysing the hydrolysis of neurotransmitter acetylcholine. As a specific molecular target of organophosphate and carbamate pesticides, acetylcholinesterase activity and its inhibition has been early recognized to be a human biological marker of pesticide poisoning. Measurement of AChE inhibition has been increasingly used in the last two decades as a biomarker of effect on nervous system follo...

  18. Acetylcholinesterase assay for cerebrospinal fluid using bupivacaine to inhibit butyrylcholinesterase

    Anders Jens; Pietsch Stefan; Bauer Heike I; Kluge Harald H; Kluge Wolfram H; Venbrocks Rudolf A

    2001-01-01

    Abstract Background Most test systems for acetylcholinesterase activity (E.C.3.1.1.7.) are using toxic inhibitors (BW284c51 and iso-OMPA) to distinguish the enzyme from butyrylcholinesterase (E.C.3.1.1.8.) which occurs simultaneously in the cerebrospinal fluid. Applying Ellman's colorimetric method, we were looking for a non-toxic inhibitor to restrain butyrylcholinesterase activity. Based on results of previous in vitro studies bupivacaine emerged to be a suitable inhibitor. Results Pharmaco...

  19. The Dynamics of Ligand Barrier Crossing inside the Acetylcholinesterase Gorge

    Bui, Jennifer M.; Henchman, Richard H.; McCammon, J. Andrew

    2003-01-01

    The dynamics of ligand movement through the constricted region of the acetylcholinesterase gorge is important in understanding how the ligand gains access to and is released from the active site of the enzyme. Molecular dynamics simulations of the simple ligand, tetramethylammonium, crossing this bottleneck region are conducted using umbrella potential sampling and activated flux techniques. The low potential of mean force obtained is consistent with the fast reaction rate of acetylcholineste...

  20. Effects of gamma radiation on solutions of acetylcholinesterase

    Dilute solutions of bovine erythrocyte acetylcholinesterase were irradiated by 30, 60, 90, and 120 krad of 60Co gamma rays under air at around 50C. The enzyme activity decreased progressively with radiation dose. Ultraviolet spectra measurements indicated conformational changes in the enzyme with radiation dose. Part of the decrease in the activity of the enzyme after irradiation by 120 krad could be accounted for by the splitting of the enzyme into two pieces of molecular weights 73,000 and 7500