Improving the acetylcholinesterase inhibitory effect of Illigera henryi by solid-state fermentation with Clonostachys rogersoniana.

Science.gov (United States)

Li, Xue-Jiao; Dong, Jian-Wei; Cai, Le; Mei, Rui-Feng; Ding, Zhong-Tao

2017-11-01

Illigera henryi, an endemic traditional Chinese medicine, contains abundant aporphine alkaloids that possess various bioactivities. In the present study, tubers of I. henryi were fermented by several fungi, and the acetylcholinesterase (AChE) inhibitory activities of non-fermented and fermented I. henryi were measured. The results showed that the fermentation of I. henryi with Clonostachys rogersoniana 828H2 is effective for improving the AChE inhibitory activity. A key biotransformation was found during the C. rogersoniana fermentation for clarifying the improvement of the AChE inhibitory activity of I. henryi: (S)-actinodaphnine (1) was converted to a new 4-hydroxyaporphine alkaloid (4R,6aS)-4-hydroxyactinodaphnine (2) that possessed a stronger AChE inhibitory activity, with an IC 50 value of 17.66±0.06 μM. This paper is the first to report that the pure strain fermentation processing of I. henryi and indicated C. rogersoniana fermentation might be a potential processing method for I. henryi. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

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

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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.

Inhibition of acetylcholinesterase activity in brain and behavioral analysis in adult rats after chronic administration of fenproporex.

Science.gov (United States)

Rezin, Gislaine T; Scaini, Giselli; Ferreira, Gabriela K; Cardoso, Mariane R; Gonçalves, Cinara L; Constantino, Larissa S; Deroza, Pedro F; Ghedim, Fernando V; Valvassori, Samira S; Resende, Wilson R; Quevedo, João; Zugno, Alexandra I; Streck, Emilio L

2012-12-01

Fenproporex is an amphetamine-based anorectic and it is rapidly converted in vivo into amphetamine. It elevates the levels of extracellular dopamine in the brain. Acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine. Thus, we investigated whether the effects of chronic administration of fenproporex in adult rats alters acquisition and retention of avoidance memory and acetylcholinesterase activity. Adult male Wistar rats received repeated (14 days) intraperitoneal injection of vehicle or fenproporex (6.25, 12.5 or 25 mg/kg i.p.). For behavioral assessment, animals were submitted to inhibitory avoidance (IA) tasks and continuous multiple trials step-down inhibitory avoidance (CMIA). Acetylcholinesterase activity was measured in the prefrontal cortex, hippocampus, hypothalamus and striatum. The administration of fenproporex (6.25, 12.5 and 25 mg/kg) did not induce impairment in short and long-term IA or CMIA retention memory in rats. In addition, longer periods of exposure to fenproporex administration decreased acetylcholinesterase activity in prefrontal cortex and striatum of rats, but no alteration was verified in the hippocampus and hypothalamus. In conclusion, the present study showed that chronic fenproporex administration decreased acetylcholinesterase activity in the rat brain. However, longer periods of exposure to fenproporex did not produce impairment in short and long-term IA or CMIA retention memory in rats.

Antimicrobial activity and acetylcholinesterase inhibition by extracts from chromatin modulated fungi

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Matheus Thomaz Nogueira Silva Lima

Full Text Available ABSTRACT Major health challenges as the increasing number of cases of infections by antibiotic multiresistant microorganisms and cases of Alzheimer's disease have led to searching new control drugs. The present study aims to verify a new way of obtaining bioactive extracts from filamentous fungi with potential antimicrobial and acetylcholinesterase inhibitory activities, using epigenetic modulation to promote the expression of genes commonly silenced. For such finality, five filamentous fungal species (Talaromyces funiculosus, Talaromyces islandicus, Talaromyces minioluteus, Talaromyces pinophilus, Penicillium janthinellum were grown or not with DNA methyltransferases inhibitors (procainamide or hydralazine and/or a histone deacetylase inhibitor (suberohydroxamic acid. Extracts from T. islandicus cultured or not with hydralazine inhibited Listeria monocytogenes growth in 57.66 ± 5.98% and 15.38 ± 1.99%, respectively. Increment in inhibition of acetylcholinesterase activity was observed for the extract from P. janthinellum grown with procainamide (100%, when compared to the control extract (39.62 ± 3.76%. Similarly, inhibition of acetylcholinesterase activity increased from 20.91 ± 3.90% (control to 92.20 ± 3.72% when the tested extract was obtained from T. pinophilus under a combination of suberohydroxamic acid and procainamide. Concluding, increases in antimicrobial activity and acetylcholinesterase inhibition were observed when fungal extracts in the presence of DNA methyltransferases and/or histone deacetylase modulators were tested.

Acetylcholinesterase and Butyrylcholinesterase Inhibitory Activities of β-Carboline and Quinoline Alkaloids Derivatives from the Plants of Genus Peganum

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Ting Zhao

2013-01-01

Full Text Available It was reported that the main chemical constituents in plants of genus Peganum were a serial of β-carboline and quinoline alkaloids. These alkaloids were quantitatively assessed for selective inhibitory activities on acetylcholinesterase (AChE and butyrylcholinesterase (BChE by in vitro Ellman method. The results indicated that harmane was the most potent selective AChE inhibitor with an IC50 of 7.11 ± 2.00 μM and AChE selectivity index (SI, IC50 of BChE/IC50 of AChE of 10.82. Vasicine was the most potent BChE inhibitor with feature of dual AChE/BChE inhibitory activity, with an IC50 versus AChE/BChE of 13.68 ± 1.25/2.60 ± 1.47 μM and AChE SI of 0.19. By analyzing and comparing the IC50 and SI of those chemicals, it was indicated that the β-carboline alkaloids displayed more potent AChE inhibition but less BChE inhibition than quinoline alkaloids. The substituent at the C7 position of the β-carboline alkaloids and C3 and C9 positions of quinoline alkaloids played a critical role in AChE or BChE inhibition. The potent inhibition suggested that those alkaloids may be used as candidates for treatment of Alzheimer’s disease. The analysis of the quantitative structure-activity relationship of those compounds investigated might provide guidance for the design and synthesis of AChE and BChE inhibitors.

2-(2-(4-Benzoylpiperazin-1-ylethylisoindoline-1,3-dione derivatives: Synthesis, docking and acetylcholinesterase inhibitory evaluation as anti-alzheimer agents

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Ahmad Mohammadi-Farani

2017-01-01

Full Text Available Objective(s: Alzheimer’s disease (AD as progressive cognitive decline and the most common form of dementia is due to degeneration of the cholinergic neurons in the brain. Therefore, administration of the acetylcholinesterase (AChE inhibitors such as donepezil is the first choice for treatment of the AD. In the present study, we focused on the synthesis and anti-cholinesterase evaluation of new donepezil like analogs. Materials and Methods: A new series of phthalimide derivatives (compounds 4a-4j were synthesized via Gabriel protocol and subsequently amidation reaction was performed using various benzoic acid derivatives. Then, the corresponding anti-acetylcholinesterase activity of the prepared derivatives (4a-4j was assessed by utilization of the Ellman's test and obtained results were compared to donepezil. Besides, docking study was also carried out to explore the likely in silico binding interactions.  Results: According to the obtained results, electron withdrawing groups (Cl, F at position 3 and an electron donating group (methoxy at position 4 of the phenyl ring enhanced the acetylcholinesterase inhibitory activity. Compound 4e (m-Fluoro, IC50 = 7.1 nM and 4i (p-Methoxy, IC50 = 20.3 nM were the most active compounds in this series and exerted superior potency than donepezil (410 nM. Moreover, a similar binding mode was observed in silico for all ligands in superimposition state with donepezil into the active site of acetylcholinesterase. Conclusion: Studied compounds could be potential leads for discovery of novel anti-Alzheimer agents in the future.

The inhibitory effect of manganese on acetylcholinesterase activity enhances oxidative stress and neuroinflammation in the rat brain

International Nuclear Information System (INIS)

Santos, Dinamene; Milatovic, Dejan; Andrade, Vanda; Batoreu, M. Camila; Aschner, Michael; Marreilha dos Santos, A.P.

2012-01-01

Highlights: ► Acetylcholinesterase (AChE) is a target of Mn in the central nervous system. ► Mn inhibits AChE, representing a novel mechanistic finding for its mode of action. ► AChE inhibition may trigger or contribute to the development of oxidative stress. ► Excess Mn can trigger the release of inflammatory mediators. ► AChE activity may serve as an early biomarker of Mn neurotoxicity. -- Abstract: Background: Manganese (Mn) is a naturally occurring element and an essential nutrient for humans and animals. However, exposure to high levels of Mn may cause neurotoxic effects. The pathological mechanisms associated with Mn neurotoxicity are poorly understood, but several reports have established it is mediated, at least in part, by oxidative stress. Objectives: The present study was undertaken to test the hypothesis that a decrease in acetylcholinesterase (AChE) activity mediates Mn-induced neurotoxicity. Methods: Groups of 6 rats received 4 or 8 intraperitoneal (i.p.) injections of 25 mg MnCl 2 /kg/day, every 48 h. Twenty-four hours after the last injection, brain AChE activity and the levels of F 2 -isoprostanes (F 2 -IsoPs) and F 4 -neuroprostanes (F 4 -NPs) (biomarkers of oxidative stress), as well as prostaglandin E 2 (PGE 2 ) (biomarker of neuroinflammation) were analyzed. Results: The results showed that after either 4 or 8 Mn doses, brain AChE activity was significantly decreased (p 2 -IsoPs and PGE 2 levels, but only after 8 doses. In rats treated with 4 Mn doses, a significant increase (p 4 -NPs levels was found. To evaluate cellular responses to oxidative stress, we assessed brain nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) and Mn-superoxide dismutase (Mn-SOD, SOD2) protein expression levels. A significant increase in Mn-SOD protein expression (p < 0.05) and a trend towards increased Nrf2 protein expression was noted in rat brains after 4 Mn doses vs. the control group, but the expression of these proteins was decreased after 8 Mn

Acetyl-cholinesterase Enzyme Inhibitory Effect of Calophyllum species

African Journals Online (AJOL)

Purpose: To search for new acetylcholinesterase enzyme inhibitors from Calopyllum species. Methods: Six stem bark extracts of Calophyllum inophyllum, C. soulattri, C. teysmannii, C. lowii, C. benjaminum and C. javanicum were subjected to anti-cholinesterase analysis against acetylcholinesterase (AChE) enzyme using ...

Antioxidant and anti-acetylcholinesterase activities of extracts from Rapistrum rugosum in Tunisia

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Omri Hichri Amel

2017-07-01

Full Text Available Objective: To investigate the antioxidant potential and anti-acetylcholinesterase activity of Rapistrum rugosum extracts. Methods: The crude, ethyl acetate, butanol and water extracts prepared from flowers, roots, stems and leaves of Rapistrum rugosum were tested at 1 mg/mL to determine their total polyphenol content, total flavonoid content and total condensed tannin content. Their antioxidant activity was assessed at different concentrations (0.0312, 0.0625, 0.1250, 0.25, 0.50 and 1.00 mg/ mL by using DPPH, ABTS, reducing power and β-carotene bleAChIng inhibition activity. Antiacetylcholinesterase activity was also determined. Results: The extract of leaves and stems had the highest total phenolic content [(110.45依0.03 mg gallic acid equivalent/g dry weight]. The ethyl acetate extract of flowers had the highest total flavonoid content [(24.62依0.13 mg quercetin equivalent/g dry weight]. The butanolic fraction of flowers had the highest total condensed tannin content [(317.85依0.01 mg catechin equivalent/g dry weight]. The crude extracts of flowers exhibited an interesting antioxidant activity for DPPH assay (93.00依0.01% at 1 mg/mL. The greatest acetylcholinesterase inhibitory activity (IC50=1.60 mg/mL was exhibited by the crude extracts from the flowers. Conclusions: The results demonstrated that Rapistrum rugosum contains active constituents which possess antioxidant and anti-acetylcholinesterase activities.

Screening for acetylcholinesterase inhibitory activity in cyanobacteria of the genus Nostoc

Czech Academy of Sciences Publication Activity Database

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

Synthesis of Novel Chalcones as Acetylcholinesterase Inhibitors

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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.

Acetylcholinesterase-Inhibiting Activity of Salicylanilide N-Alkylcarbamates and Their Molecular Docking

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Josef Jampilek

2012-08-01

Full Text Available A series of twenty-five novel salicylanilide N-alkylcarbamates were investigated as potential acetylcholinesterase inhibitors. The compounds were tested for their ability to inhibit acetylcholinesterase (AChE from electric eel (Electrophorus electricus L.. Experimental lipophilicity was determined, and the structure-activity relationships are discussed. The mode of binding in the active site of AChE was investigated by molecular docking. All the discussed compounds expressed significantly higher AChE inhibitory activity than rivastigmine and slightly lower than galanthamine. Disubstitution by chlorine in C'_(3,4 of the aniline ring and the optimal length of hexyl-undecyl alkyl chains in the carbamate moiety provided the most active AChE inhibitors. Monochlorination in C'₍₄ exhibited slightly more effective AChE inhibitors than in C'₍₃. Generally it can be stated that compounds with higher lipophilicity showed higher inhibition, and the activity of the compounds is strongly dependent on the length of the N-alkyl chain.

Screening of plants used in the European traditional medicine to treat memory disorders for acetylcholinesterase inhibitory activity and anti amyloidogenic activity

DEFF Research Database (Denmark)

Lobbens, Eva S B; Vissing, Karina J.; Jorgensen, Lene

2017-01-01

and the ability to inhibit the enzymatic activity of acetylcholinesterase was evaluated monitoring the hydrolysis of acetylthiocholine Results Under the experimental conditions investigated, extracts of two plants, Carum carvi and Olea sylvestris, inhibited amyloid beta fibrillation considerably, eight plant...

Phytochemical Quantification and the In Vitro Acetylcholinesterase Inhibitory Activity of Phellodendron chinense and Its Components.

Science.gov (United States)

Kim, Yu Jin; Lim, Hye-Sun; Kim, Yoonju; Lee, Jun; Kim, Bu-Yeo; Jeong, Soo-Jin

2017-06-02

The dried bark of Phellodendron chinense has been used as a traditional herbal medicine to remove damp heat, relieve consumptive fever, and cure dysentery and diarrhea. In the present study, we performed quantitative analyses of the two components of P. chinense , phellodendrine and berberine, using high-performance liquid chromatography. A 70% ethanol extract of P. chinense was prepared and the two components were separated on a C-18 analytical column using a gradient solvent system of acetonitrile and 0.1% ( v / v ) aqueous trifluoroacetic acid. The ultraviolet wavelength used for detection was 200 nm for phellodendrine and 226 nm for berberine. The analytical method established here showed high linearity (correlation coefficient, ≥0.9991). The amount of phellodendrine and berberine used was 22.255 ± 0.123 mg/g and 269.651 ± 1.257 mg/g, respectively. Moreover, we performed an in vitro acetylcholinesterase (AChE) activity assay and an amyloid-β aggregation test to examine the biological properties of phellodendrine and berberine as therapeutic drugs for Alzheimer's disease. Phellodendrine and berberine inhibited AChE activity in a dose-dependent manner (IC 50 = 36.51 and 0.44 μM, respectively). In contrast, neither phellodendrine nor berberine had an effect on amyloid-β aggregation. The P. chinense extract and phellodendrine, but not berberine, exhibited antioxidant activity by increasing radical scavenging activity. Moreover, P. chinense demonstrated a neuroprotective effect in hydrogen peroxide-treated HT22 hippocampal cells. Overall, our findings suggest that P. chinense has potential as an anti-Alzheimer's agent via the suppression of the enzymatic activity of acetylcholinesterase and the stimulation of antioxidant activity.

Chitooligosaccharides suppress the level of protein expression and acetylcholinesterase activity induced by Abeta25-35 in PC12 cells.

Science.gov (United States)

Lee, Sang-Hoon; Park, Jin-Sook; Kim, Se-Kwon; Ahn, Chang-Bum; Je, Jae-Young

2009-02-01

Clinical applications of acetylcholinesterase (AChE) inhibitors are widespread in Alzheimer's sufferers in order to activate central cholinergic system and alleviate cognitive deficits by inhibiting the hydrolysis of acetylcholine. In this study, six kinds of chitooligosaccharides (COSs) with different molecular weight and degree of deacetylation were examined for their inhibitory effects against AChE. The 90-COSs exhibited potent AChE inhibitory activities compared to 50-COSs, while 90-MMWCOS (1000-5000 Da) in the 90-COSs showed the highest activity. Cell culture experiment revealed that 90-MMWCOS suppressed the level of AChE protein expression and AChE activity induced by Abeta(25-35) in PC12 cell lines.

Screening of acetylcholinesterase inhibitors in marine organisms from the Caribbean Sea.

Science.gov (United States)

Castellanos, Fabio; Amaya-García, Fabián; Tello, Edisson; Ramos, Freddy Alejandro; Umaña, Adriana; Puyana, Mónica; Resende, Jackson A L C; Castellanos, Leonardo

2018-06-04

The acetylcholinesterase inhibitory activity of 89 organic extracts from marine organisms was evaluated through a TLC bioautography methodology. Extracts from soft corals (Eunicea and Plexaura) were the most active compared with extracts from sponges. The bioguided chemical study of the most active extract, obtained from Pseudoplexaura porosa, led to the isolation of a diterpene with spectroscopic properties consistent to those published to the cembrane Steylolide. However, further analysis by X-ray diffraction indicated that the compound was the 14-acetoxycrassine (1), correcting the structure reported to the Styelolide. Additionally, the acetylcholinesterase inhibitory activity of fourteen cembranoids (2-15) isolated from soft corals Eunicea knighti and Pseudoplexaura flagellosa was evaluated. Cembranoids 2, 3 and 4 were the most active compounds in the TLC bioassay. Then, the most promising cembranoids, 14-acetoxycrassine (1) and asperdiol (2), were tested quantitatively and they exhibited IC 50 values of 1.40 ± 0.113 and 0.358 ± 0.130 μM, respectively.

Antioxidant Activity and Acetylcholinesterase Inhibition of Grape Skin Anthocyanin (GSA

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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.

Cholinesterase inhibitory activity and structure elucidation of a new phytol derivative and a new cinnamic acid ester from Pycnanthus angolensis

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Taiwo O. Elufioye

Full Text Available ABSTRACT The leaves of Pycnanthus angolensis (Welw. Warb., Myristicaceae, are used as memory enhancer and anti-ageing in Nigerian ethnomedicine. This study aimed at evaluating the cholinesterase inhibitory property as well as isolates the bioactive compounds from the plant. The acetylcholinesterase and butyrylcholinesterase inhibitory potentials of extracts, fractions, and isolated compounds were evaluated by colorimetric and TLC bioautographic assay techniques. The extract inhibited both enzymes with activity increasing with purification, ethyl acetate fraction being most active fraction at 65.66 ± 1.06% and 49.38 ± 1.66% against acetylcholinesterase and butyrylcholinesterase, respectively while the supernatant had 77.44 ± 1.18 inhibition against acetylcholinesterase. Two new bioactive compounds, (2E, 18E-3,7,11,15,18-pentamethylhenicosa-2,18-dien-1-ol (named eluptol and [12-(4-hydroxy-3-methyl-oxo-cyclopenta-1,3-dien-1yl-11-methyl-dodecyl](E-3-(3,4-dimethylphenylprop-2-enoate (named omifoate A were isolated from the plant with IC50 of 22.26 µg/ml (AChE, 34.61 µg/ml (BuChE and 6.51 µg/ml (AChE, 9.07 µg/ml (BuChE respectively. The results showed that the plant has cholinesterase inhibitory activity which might be responsible for its memory enhancing action, thus justifying its inclusion in traditional memory enhancing preparations

Design, synthesis and structure-activity relationships of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease.

Science.gov (United States)

Toda, Narihiro; Tago, Keiko; Marumoto, Shinji; Takami, Kazuko; Ori, Mayuko; Yamada, Naho; Koyama, Kazuo; Naruto, Shunji; Abe, Kazumi; Yamazaki, Reina; Hara, Takao; Aoyagi, Atsushi; Abe, Yasuyuki; Kaneko, Tsugio; Kogen, Hiroshi

2003-05-01

We have designed and synthesized a dual inhibitor of acetylcholinesterase (AChE) and serotonin transporter (SERT) as a novel class of treatment drugs for Alzheimer's disease on the basis of a hypothetical model of the AChE active site. Dual inhibitions of AChE and SERT would bring about greater therapeutic effects than AChE inhibition alone and avoid adverse peripheral effects caused by excessive AChE inhibition. Compound (S)-6j exhibited potent inhibitory activities against AChE (IC(50)=101 nM) and SERT (IC(50)=42 nM). Furthermore, (S)-6j showed inhibitory activities of both AChE and SERT in mice brain following oral administration.

Acetyl-cholinesterase Enzyme Inhibitory Effect of Calophyllum species

African Journals Online (AJOL)

1Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, ... Purpose: To search for new acetylcholinesterase enzyme inhibitors from ... Index Medicus, JournalSeek, Journal Citation Reports/Science Edition, .... The data are expressed as mean ± standard .... The authors acknowledge financial support from.

A simple radiometric in vitro assay for acetylcholinesterase inhibitors

International Nuclear Information System (INIS)

Guilarte, T.R.; Burns, H.D.; Dannals, R.F.; Wagner, H.N. Jr.

1983-01-01

A radiometric method for screening acetylcholinesterase inhibitors has been described. The method is based on the production of [ 14 C]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

Phytochemical profiles, antioxidant and anti-acetylcholinesterasic activities of the leaf extracts of Rhamnus lycioides subsp. oleoides (L.) Jahand. & Maire in different solvents.

Science.gov (United States)

Benamar, Houari; Rarivoson, Elonge; Tomassini, Lamberto; Frezza, Claudio; Marouf, Abderrazak; Bennaceur, Malika; Nicoletti, Marcello

2018-01-05

In this work, the extracts obtained with different solvents from the leaves of Rhamnus lycioides subsp. oleoides (L.) Jahand. & Maire were studied for their phytochemical profile and then for their antioxidant and acetylcholinesterase inhibitory activities. The phytochemical profiles of the extracts in n-hexane, dichloromethane, ethyl acetate, methanol, anthraquinone rich and water, showed the presence of different compounds belonging to several classes of natural products such as flavonoids, anthraquinones, saccharides and fatty acids. For what concerns the biological tests, the ethyl acetate, methanol and anthraquinone rich extracts showed the highest activities in both assays due to the high amount of compounds possessing those properties such as flavonoids and anthraquinones. By consequence, these specific extracts of the species may be considered to be potential sources of natural antioxidant and anti-acetylcholinesterasic compounds.

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

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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.

Novel coumarin derivatives bearing N-benzyl pyridinium moiety: potent and dual binding site acetylcholinesterase inhibitors.

Science.gov (United States)

Alipour, Masoumeh; Khoobi, Mehdi; Foroumadi, Alireza; Nadri, Hamid; Moradi, Alireza; Sakhteman, Amirhossein; Ghandi, Mehdi; Shafiee, Abbas

2012-12-15

A novel series of coumarin derivatives linked to benzyl pyridinium group were synthesized and biologically evaluated as inhibitors of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The enzyme inhibitory activity of synthesized compounds was measured using colorimetric Ellman's method. It was revealed that compounds 3e, 3h, 3l, 3r and 3s have shown higher activity compared with donepezil hydrochloride as standard drug. Most of the compounds in these series had nanomolar range IC(50) in which compound 3r (IC(50) = 0.11 nM) was the most active compound against acetylcholinesterase enzyme. Copyright © 2012 Elsevier Ltd. All rights reserved.

Design and synthesis of dual inhibitors of acetylcholinesterase and serotonin transporter targeting potential agents for Alzheimer's disease.

Science.gov (United States)

Kogen, Hiroshi; Toda, Narihiro; Tago, Keiko; Marumoto, Shinji; Takami, Kazuko; Ori, Mayuko; Yamada, Naho; Koyama, Kazuo; Naruto, Shunji; Abe, Kazumi; Yamazaki, Reina; Hara, Takao; Aoyagi, Atsushi; Abe, Yasuyuki; Kaneko, Tsugio

2002-10-03

Highly efficient acetylcholinesterase (AChE) and serotonin transporter (SERT) dual inhibitors, (S)-4 and (R)-13 were designed and synthesized on the basis of the hypothetical model of AChE active site. Both compounds showed potent inhibitory activities against AChE and SERT. [structure: see text

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

Science.gov (United States)

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.

Acute administration of fenproporex increased acetylcholinesterase activity in brain of young rats.

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Teodorak, Brena P; Ferreira, Gabriela K; Scaini, Giselli; Wessler, Letícia B; Heylmann, Alexandra S; Deroza, Pedro; Valvassori, Samira S; Zugno, Alexandra I; Quevedo, João; Streck, Emilio L

2015-08-01

Fenproporex is the second most commonly amphetamine-based anorectic consumed worldwide; this drug is rapidly converted into amphetamine, in vivo, and acts by increasing dopamine levels in the synaptic cleft. Considering that fenproporex effects on the central nervous system are still poorly known and that acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine, the present study investigated the effects of acute administration of fenproporex on acetylcholinesterase activity in brain of young rats. Young male Wistar rats received a single injection of fenproporex (6.25, 12.5 or 25mg/kg i.p.) or vehicle (2% Tween 80). Two hours after the injection, the rats were killed by decapitation and the brain was removed for evaluation of acetylcholinesterase activity. Results showed that fenproporex administration increased acetylcholinesterase activity in the hippocampus and posterior cortex, whereas in the prefrontal cortex, striatum and cerebellum the enzyme activity was not altered. In conclusion, in the present study we demonstrated that acute administration of fenproporex exerts an effect in the cholinergic system causing an increase in the activity of acetylcholinesterase in a dose-dependent manner in the hippocampus and posterior cortex. Thus, we suggest that the imbalance in cholinergic homeostasis could be considered as an important pathophysiological mechanism underlying the brain damage observed in patients who use amphetamines such as fenproporex.

Acute administration of fenproporex increased acetylcholinesterase activity in brain of young rats

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BRENA P. TEODORAK

2015-08-01

Full Text Available Fenproporex is the second most commonly amphetamine-based anorectic consumed worldwide; this drug is rapidly converted into amphetamine, in vivo, and acts by increasing dopamine levels in the synaptic cleft. Considering that fenproporex effects on the central nervous system are still poorly known and that acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine, the present study investigated the effects of acute administration of fenproporex on acetylcholinesterase activity in brain of young rats. Young male Wistar rats received a single injection of fenproporex (6.25, 12.5 or 25mg/kg i.p. or vehicle (2% Tween 80. Two hours after the injection, the rats were killed by decapitation and the brain was removed for evaluation of acetylcholinesterase activity. Results showed that fenproporex administration increased acetylcholinesterase activity in the hippocampus and posterior cortex, whereas in the prefrontal cortex, striatum and cerebellum the enzyme activity was not altered. In conclusion, in the present study we demonstrated that acute administration of fenproporex exerts an effect in the cholinergic system causing an increase in the activity of acetylcholinesterase in a dose-dependent manner in the hippocampus and posterior cortex. Thus, we suggest that the imbalance in cholinergic homeostasis could be considered as an important pathophysiological mechanism underlying the brain damage observed in patients who use amphetamines such as fenproporex.

Dihydroagarofuranoid Sesquiterpenes as Acetylcholinesterase Inhibitors from Celastraceae Plants: Maytenus disticha and Euonymus japonicus.

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Alarcón, Julio; Cespedes, Carlos L; Muñoz, Evelyn; Balbontin, Cristian; Valdes, Francisco; Gutierrez, Margarita; Astudillo, Luis; Seigler, David S

2015-12-02

Natural cholinesterase inhibitors have been found in many biological sources. Nine compounds with agarofuran (epoxyeudesmane) skeletons were isolated from seeds and aerial parts of Maytenus disticha and Euonymus japonicus. The identification and structural elucidation of compounds were based on spectroscopic data analyses. All compounds had inhibitory acetylcholinesterase (AChE) activity. These natural compounds, which possessed mixed or uncompetitive mechanisms of inhibitory activity against AChE, may be considered as models for the design and development of new naturally occurring drugs for management strategies for neurodegenerative diseases. This is the first report of these chemical structures for seeds of M. disticha.

A novel biosensor method for surfactant determination based on acetylcholinesterase inhibition

International Nuclear Information System (INIS)

Kucherenko, I S; Soldatkin, O O; Arkhypova, V M; Dzyadevych, S V; Soldatkin, A P

2012-01-01

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. (paper)

Changes in acetylcholinesterase activities in the developing and ...

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Changes in acetylcholinesterase activities in the developing and aging pig brain and hypophyses. ... International Journal of Agriculture and Rural Development. Journal Home · ABOUT ... Open Access DOWNLOAD FULL TEXT Subscription ...

Acetylcholinesterase Inhibition and Antioxidant Activity of N-trans-Caffeoyldopamine and N-trans-Feruloyldopamine

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Muamer Dizdar

2018-04-01

Full Text Available Phenolic acids and their derivatives found in nature are well-known for their potential biological activity. In this study, two amides derived from trans-caffeic/ferulic acid and dopamine were synthesized and characterized by Fourier-transform infrared spectroscopy (FTIR, mass spectrometry, proton and carbon-13 nuclear magnetic resonance spectroscopy. The compounds were tested for the inhibition of acetylcholinesterase (AChE from Electrophorus electricus and for antioxidant activity by scavenging 2,2-diphenyl-1-pycrylhydrazyl free radical (DPPH• and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulphonic acid radical cation (ABTS•+, reducing ferric ions, and ferrous ions chelation. N-trans-Feruloyldopamine displayed the highest inhibitory effect on AChE with half-maximal inhibitory concentration (IC50 values of 8.52 μM. In addition, an in silico study was done to determine the most favorable AChE cluster with the synthesized compounds. Further, these clusters were investigated for binding positions at the lowest free binding energy. Both synthesized hydroxycinnamates were found to be better antioxidants than the parent acids in in vitro tests applied. N-trans-Caffeoyldopamine showed the best antioxidant activity in the three tested methods—against non-biological stable free radicals IC50 5.95 μM for DPPH•, 0.24 μM for the ABTS•+ method, and for reducing power (ascorbic acid equivalent (AAE 822.45 μmol/mmol—while for chelation activity against Fe2+ ions N-trans-feruloyldopamine had slightly better antioxidant activity (IC50 3.17 mM.

New Indole Alkaloids from the Bark of Rauvolfia Reflexa and their Cholinesterase Inhibitory Activity

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Mehran Fadaeinasab

2015-11-01

Full Text Available Background/Aims: Rauvolfia reflexa is a member of the Apocynaceae family. Plants from the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders Methods and Results: Two new indole alkaloids, rauvolfine C (1 and 3-methyl-10,11-dimethoxy-6-methoxycarbonyl-β-carboline (2, along with five known, macusine B (3, vinorine (4, undulifoline (5, isoresrpiline (6 and rescinnamine (7 were isolated from the bark of Rauvolfia reflexa. Cholinesterase inhibitory assay and molecular docking were performed to get insight of the inhibitory activity and molecular interactions of the compounds. The compounds showed good to moderate cholinesterase inhibitory activity with IC50 values in the range of 8.06 to 73.23 µM. Compound 7 was found to be the most potent inhibitor of both acetylcholinesterase (AChE and butyrylcholinesterase (BChE. Compounds 1, 2, 5 and 6 were found to be selective towards BChE, while compounds 3, 4 and 7 were dual inhibitors, having almost equal inhibitory activity on both AChE and BChE. Molecular docking revealed that compounds 6 and 7 interacted differently on AChE and BChE, by means of hydrophobic interactions and hydrogen bonding. In AChE, the indole moiety of both compounds interacted with the residues lining the peripheral anionic site, whereas in BChE, their methoxy groups are primarily responsible for the strong inhibitory activity via interactions with residues at the active site of the enzyme. Conclusion: Two new and five known indole alkaloids were isolated from R. reflexa. Among the compounds, 7 and 6 showed the most potent and promising cholinesterase inhibitory activity, worthy for further investigations.

New Indole Alkaloids from the Bark of Rauvolfia Reflexa and their Cholinesterase Inhibitory Activity.

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Fadaeinasab, Mehran; Basiri, Alireza; Kia, Yalda; Karimian, Hamed; Ali, Hapipah Mohd; Murugaiyah, Vikneswaran

2015-01-01

Rauvolfia reflexa is a member of the Apocynaceae family. Plants from the Apocynaceae family have been traditionally used in the treatment of age-related brain disorders Methods and Results: Two new indole alkaloids, rauvolfine C (1) and 3-methyl-10,11-dimethoxy-6-methoxycarbonyl-β-carboline (2), along with five known, macusine B (3), vinorine (4), undulifoline (5), isoresrpiline (6) and rescinnamine (7) were isolated from the bark of Rauvolfia reflexa. Cholinesterase inhibitory assay and molecular docking were performed to get insight of the inhibitory activity and molecular interactions of the compounds. The compounds showed good to moderate cholinesterase inhibitory activity with IC50 values in the range of 8.06 to 73.23 µM. Compound 7 was found to be the most potent inhibitor of both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Compounds 1, 2, 5 and 6 were found to be selective towards BChE, while compounds 3, 4 and 7 were dual inhibitors, having almost equal inhibitory activity on both AChE and BChE. Molecular docking revealed that compounds 6 and 7 interacted differently on AChE and BChE, by means of hydrophobic interactions and hydrogen bonding. In AChE, the indole moiety of both compounds interacted with the residues lining the peripheral anionic site, whereas in BChE, their methoxy groups are primarily responsible for the strong inhibitory activity via interactions with residues at the active site of the enzyme. Two new and five known indole alkaloids were isolated from R. reflexa. Among the compounds, 7 and 6 showed the most potent and promising cholinesterase inhibitory activity, worthy for further investigations. © 2015 S. Karger AG, Basel.

Xanthone and Flavone Derivatives as Dual Agents with Acetylcholinesterase Inhibition and Antioxidant Activity as Potential Anti-Alzheimer Agents

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Inês Cruz

2017-01-01

Full Text Available Alzheimer’s disease (AD is a multifactorial neurodegenerative disorder that is associated with the elderly. The current therapy that is used to treat AD is based mainly on the administration of acetylcholinesterase (AChE inhibitors. Due to their low efficacy there is a considerable need for other therapeutic strategies. Considering that the malfunctions of different, but interconnected, biochemical complex pathways play an important role in the pathogenesis of this disease, a promising therapy may consist in administration of drugs that act on more than a target on biochemical scenery of AD. In this work, the synthesis and evaluation of xanthone and flavone derivatives as antioxidants with AChE inhibitory activity were accomplished. Among the obtained compounds, Mannich bases 3 and 14 showed capacity to inhibit AChE and antioxidant property, exerting dual activity. Moreover, for the most promising AChE inhibitors, docking studies on the target have been performed aiming to predict the binding mechanism. The results presented here may help to identify new xanthone and flavone derivatives as dual anti-Alzheimer agents with AChE inhibitory and antioxidant activities.

Novel hybrids of oxoisoaporphine-tryptamine as acetylcholinesterase-induced β-amyloid aggregation inhibitors with improved antioxidant properties

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Zhao Hai-Tao

2015-01-01

Full Text Available A series of dual binding site acetylcholinesterase (AChE inhibitors have been designed, synthesized, and tested for their antioxidant ability and inhibitory potency on AChE and AChE-induced b-amyloid (Ab aggregation. The new hybrids consist of a unit of 1-azabenzanthrone and a tryptamine or its derivative, connected through a a,w - alkyldiamide bridge. These hybrids exhibit moderate AChE inhibitory activity with IC50 values in the micromolar range and significant in vitro inhibitory activity toward the AChE-induced Ab aggregation. Moreover, six out of the nine hybrids of this series exhibit a higher oxygen radical absorbance capacity than trolox, which makes them promising anti-Alzheimer drug candidates.

Inhibitory effect of ebselen on cerebral acetylcholinesterase activity in vitro: kinetics and reversibility of inhibition.

Science.gov (United States)

Martini, Franciele; Bruning, César Augusto; Soares, Suelen Mendonca; Nogueira, Cristina Wayne; Zeni, Gilson

2015-01-01

Ebselen is a synthetic organoselenium compound that has been considered a potential pharmacological agent with low toxicity, showing antioxidant, anti-inflammatory and neuroprotective effects. It is bioavailable, blood-brain barrier permeant and safe based on cellular toxicity and Phase I-III clinical trials. There is evidence that ebselen inhibits acetylcholinesterase (AChE) activity, an enzyme that plays a key role in the cholinergic system by hydrolyzing acetylcholine (ACh), in vitro and ex vivo. This system has a well-known relationship with cognitive process, and AChE inhibitors, such as donepezil and galantamine, have been used to treat cognitive deficits, mainly in the Alzheimer's Disease (AD). However, these drugs have poor bioavailability and a number of side effects, including gastrointestinal upsets and hepatotoxicity. In this way, this study aimed to evaluate the effect of ebselen on cerebral AChE activity in vitro and to determine the kinetic profile and the reversibility of inhibition by dialysis. Ebselen inhibited the cerebral AChE activity with an IC50 of 29 µM, similar to IC50 found with pure AChE from electric eel, demonstrating a mixed and reversible inhibition of AChE, since it increased Km and decreased Vmax. The AChE activity was recovered within 60 min of dialysis. Therefore, the use of ebselen as a therapeutic agent for treatment of AD should be considered, although memory behavior tasks are needed to support such hypothesis.

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

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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. Copyright © 2015 Elsevier B.V. All rights reserved.

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

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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.

Arisugacins A and B, novel and selective acetylcholinesterase inhibitors from Penicillium sp. FO-4259. I. Screening, taxonomy, fermentation, isolation and biological activity.

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Kuno, F; Otoguro, K; Shiomi, K; Iwai, Y; Omura, S

1996-08-01

An in vitro screening method for selective acetylcholinesterase (AChE) inhibitors was established. Inhibitory activity of AChE and butyrylcholinesterase (BuChE) was measured and the culture broths of microorganisms that showed selective inhibition against AChE were characterized. By using this method, a strain producing the novel and selective inhibitors of AChE, arisugacins A and B, was picked out among over seven thousand microorganisms tested. Arisugacins were obtained as white powders from the culture broth together with three known compounds, territrems B and C and cyclopenin that also showed selective inhibition against AChE. Arisugacins and territrems are members of the meroterpenoid compounds. They showed potent inhibitory activities against AChE with IC50 values in range of 1.0 approximately 25.8 nM. Furthermore, they showed greater than 2,000-fold more potent inhibition against AChE than BuChE.

Chemical Composition and Cholinesterase Inhibitory Activity of Different Parts of Daucus aristidis Coss. Essential Oils from Two Locations in Algeria

OpenAIRE

Mebarka Lamamra; Hocine Laouer; Smain Amira; Ilkay Erdogan Orhan; Fatma Sezer Senol; Betul Demirci; Salah Akkal

2017-01-01

The chemical composition of the essential oils obtained by hydrodistillation from the different parts of Daucus aristidis Coss. (syn. Ammiopsis aristidis Batt.) (Apiaceae) from two locations (Ghoufi and Bousaada) in East of Algeria, was investigated for the first time by GC and GC-MS and evaluated for their in vitro acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity, the enzymes linked to Alzheimer’s disease, by a spectrophotometric method of Ellman using ELISA m...

Rapid Screening and Characterization of Acetylcholinesterase Inhibitors from Yinhuang Oral Liquid Using Ultrafiltration-liquid Chromatography-electrospray Ionization Tandem Mass Spectrometry.

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Zhang, Haomin; Guo, Yinan; Meng, Lingwen; Sun, Hui; Yang, Yinping; Gao, Ying; Sun, Jiaming

2018-01-01

At present, approximately 17-25 million people in the world suffer from Alzheimer's disease (AD). The most efficacious and acceptable therapeutic drug clinically are the acetylcholinesterase inhibitors (AChEIs). Yinhuang oral liquid is a Chinese medicine preparation which contains AChEIs according to the literatures. However, no strategy has been presented for rapid screening and identification of AChEIs from Yinhuang oral liquid. To develop a method for rapid screening and identification of AChEIs from Yinhuang oral liquid using ultrafiltration-liquid chromatography-electrospray ionization tandem mass spectrometry (UF-LC-ESI-MS/MS). In this study, UF incubation conditions such as enzyme concentration, incubation time, and incubation temperature were optimized so as to get better screening results. The AChEIs from Yinhuang oral liquid were identified by high-performance liquid chromatography-ESI-MS and the improved Ellman method was used for the AChE inhibitory activity test in vitro . The results showed that Yinhuang oral liquid can inhibit the activity of AChE. We screened and identified seven compounds with potential AChE inhibitory activity from Yinhuang oral liquid, which provided experimental basis for the treatment and prevention of AD. The current technique was used to directly screen the active ingredients with acetylcholinesterase inhibition from complex traditional Chinese medicine, which was simple, rapid, accurate, and suitable for high-throughput screening of AChEI from complex systems. A UF-LC-ESI-MS/MS method for rapid screening and identification of AChEIs from Yinhuang oral liquid was developedSeven compounds were screened and identified with potential AChE inhibitory activity from Yinhuang oral liquidIt provided experimental basis of Yinhuang oral liquid for the treating and preventing AD. Abbreviations used: (AD): Alzheimer's disease; (UF-LC-ESI-MS/MS): ultrafiltration-liquid chromatography-electrospray ionization tandem mass spectrometry; (ACh

Rapid Screening and Characterization of Acetylcholinesterase Inhibitors from Yinhuang Oral Liquid Using Ultrafiltration-liquid Chromatography-electrospray Ionization Tandem Mass Spectrometry

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Zhang, Haomin; Guo, Yinan; Meng, Lingwen; Sun, Hui; Yang, Yinping; Gao, Ying; Sun, Jiaming

2018-01-01

Background: At present, approximately 17–25 million people in the world suffer from Alzheimer's disease (AD). The most efficacious and acceptable therapeutic drug clinically are the acetylcholinesterase inhibitors (AChEIs). Yinhuang oral liquid is a Chinese medicine preparation which contains AChEIs according to the literatures. However, no strategy has been presented for rapid screening and identification of AChEIs from Yinhuang oral liquid. Objective: To develop a method for rapid screening and identification of AChEIs from Yinhuang oral liquid using ultrafiltration–liquid chromatography–electrospray ionization tandem mass spectrometry (UF-LC-ESI-MS/MS). Materials and Methods: In this study, UF incubation conditions such as enzyme concentration, incubation time, and incubation temperature were optimized so as to get better screening results. The AChEIs from Yinhuang oral liquid were identified by high-performance liquid chromatography-ESI-MS and the improved Ellman method was used for the AChE inhibitory activity test in vitro. Results: The results showed that Yinhuang oral liquid can inhibit the activity of AChE. We screened and identified seven compounds with potential AChE inhibitory activity from Yinhuang oral liquid, which provided experimental basis for the treatment and prevention of AD. Conclusion: The current technique was used to directly screen the active ingredients with acetylcholinesterase inhibition from complex traditional Chinese medicine, which was simple, rapid, accurate, and suitable for high-throughput screening of AChEI from complex systems. SUMMARY A UF-LC-ESI-MS/MS method for rapid screening and identification of AChEIs from Yinhuang oral liquid was developedSeven compounds were screened and identified with potential AChE inhibitory activity from Yinhuang oral liquidIt provided experimental basis of Yinhuang oral liquid for the treating and preventing AD. Abbreviations used: (AD): Alzheimer's disease; (UF

Cholinesterase inhibitory activity and chemical constituents of Stenochlaena palustris fronds at two different stages of maturity

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Nelson Jeng-Yeou Chear

2016-04-01

Full Text Available Stenochlaena palustris fronds are popular as a vegetable in Southeast Asia. The objectives of this study were to evaluate the anticholinesterase properties and phytochemical profiles of the young and mature fronds of this plant. Both types of fronds were found to have selective inhibitory effect against butyrylcholinesterase compared with acetylcholinesterase. However, different sets of compounds were responsible for their activity. In young fronds, an antibutyrylcholinesterase effect was observed in the hexane extract, which was comprised of a variety of aliphatic hydrocarbons, fatty acids, and phytosterols. In the mature fronds, inhibitory activity was observed in the methanol extract, which contained a series of kaempferol glycosides. Our results provided novel information concerning the ability of S. palustris to inhibit cholinesterase and its phytochemical profile. Further research to investigate the potential use of this plant against Alzheimer's disease is warranted, however, young and mature fronds should be distinguished due to their phytochemical differences.

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

Energy Technology Data Exchange (ETDEWEB)

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)

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

International Nuclear Information System (INIS)

Zhang, Sh.; Li, Sh.; Ma, J.; Xiong, F.; Qu, S.; Zhang, Sh.; Li, Sh.

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 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

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

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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

Synthesis of Amide and Ester Derivatives of Cinnamic Acid and Its Analogs: Evaluation of Their Free Radical Scavenging and Monoamine Oxidase and Cholinesterase Inhibitory Activities.

Science.gov (United States)

Takao, Koichi; Toda, Kazuhiro; Saito, Takayuki; Sugita, Yoshiaki

2017-01-01

A series of cinnamic acid derivatives, amides (1-12) and esters (13-22), were synthesized, and structure-activity relationships for antioxidant activity, and monoamine oxidases (MAO) A and B, acetylcholinesterase, and butyrylcholinesterase (BChE) inhibitory activities were analyzed. Among the synthesized compounds, compounds 1-10, 12-18, and rosmarinic acid (23), which contained catechol, o-methoxyphenol or 5-hydroxyindole moieties, showed potent 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity. Compounds 9-11, 15, 17-22 showed potent and selective MAO-B inhibitory activity. Compound 20 was the most potent inhibitor of MAO-B. Compounds 18 and 21 showed moderate BChE inhibitory activity. In addition, compound 18 showed potent antioxidant activity and MAO-B inhibitory activity. In a comparison of the cinnamic acid amides and esters, the amides exhibited more potent DPPH free radical scavenging activity, while the esters showed stronger inhibitory activities against MAO-B and BChE. These results suggested that cinnamic acid derivatives such as compound 18, p-coumaric acid 3,4-dihydroxyphenethyl ester, and compound 20, p-coumaric acid phenethyl ester, may serve as lead compounds for the development of novel MAO-B inhibitors and candidate lead compounds for the prevention or treatment of Alzheimer's disease.

Inhibition of acetylcholinesterase activity by essential oil from Citrus paradisi.

Science.gov (United States)

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.

A New Acetylcholinesterase Inhibitor from Green Glycosylation of Trachyloban-19-oic Acid by Mucor plumbeus.

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Santos, Gabriel F Dos; Takahashi, Jacqueline A

2017-01-01

The in vitro metabolism of a widespread natural product, trachyloban-19-oic acid (1), by the fungal species Mucor plumbeus was studied in a sucrose-yeast liquid medium. Two products were isolated, and their structures were determined by spectroscopic means as 7β-hydroxytrachyloban-19-oic acid (5) and trachyloban-19-O-β-D-glucopyranosyl ester (6). To the best of our knowledge, compound 6 is herein reported by the first time in the literature. These compounds were assayed for acetylcholinesterase inhibition along with some related compounds. Compound 6 showed the highest acetylcholinesterase inhibitory activity at 10000 µg/mL among the tested compounds, a result (92.89%) comparable to the activity of the positive control, galanthamine (94.21%). Therefore, biotransformation of the natural product 1 by M. plumbeus produced a novel compound with potential as a new lead to develop anti-Alzheimer medicines.

A New Acetylcholinesterase Inhibitor from Green Glycosylation of Trachyloban-19-oic Acid by Mucor plumbeus

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GABRIEL F. DOS SANTOS

2017-10-01

Full Text Available ABSTRACT The in vitro metabolism of a widespread natural product, trachyloban-19-oic acid (1, by the fungal species Mucor plumbeus was studied in a sucrose-yeast liquid medium. Two products were isolated, and their structures were determined by spectroscopic means as 7β-hydroxytrachyloban-19-oic acid (5 and trachyloban-19-O-β-D-glucopyranosyl ester (6. To the best of our knowledge, compound 6 is herein reported by the first time in the literature. These compounds were assayed for acetylcholinesterase inhibition along with some related compounds. Compound 6 showed the highest acetylcholinesterase inhibitory activity at 10000 µg/mL among the tested compounds, a result (92.89% comparable to the activity of the positive control, galanthamine (94.21%. Therefore, biotransformation of the natural product 1 by M. plumbeus produced a novel compound with potential as a new lead to develop anti-Alzheimer medicines.

Synthesis and study of thiocarbonate derivatives of choline as potential inhibitors of acetylcholinesterase.

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Boyle, N A; Talesa, V; Giovannini, E; Rosi, G; Norton, S J

1997-09-12

Fourteen alkyl and aryl thiocarbonate derivatives of choline were synthesized and studied as potential inhibitors of acetylcholinesterase (AChE). Twelve of the compounds inhibited AChEs derived from calf forebrain, human red blood cells, and octopus brain ranging from low to moderately high inhibition potency. The concentration of each inhibitory compound giving 50% inhibition of enzyme activity (IC50 values, which ranged from 1 x 10(-2) to 8 x 10(-7) M) was determined and is reported; inhibitor constants (Ki values) for the most inhibitory compounds, (1-pentylthiocarbonyl)choline chloride and (1-heptylthiocarbonyl)choline chloride, were calculated from kinetic data and are also reported. The inhibitors are competitive with substrate, and they are not hydrolyzed by the AChE activities. Certain of these new compounds may provide direction for the development of new drugs that have anticholinesterase activity and may be used for the treatment of Alzheimer's disease.

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

OpenAIRE

Arruda, Miguel; Viana, Hugo; Rainha, Nuno; Neng, Nuno R.; Rosa, José Silvino; Nogueira, José M. F.; Barreto, Maria do Carmo

2012-01-01

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 composi...

Brain acetylcholinesterase activity controls systemic cytokine levels through the cholinergic anti-inflammatory pathway

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Pavlov, Valentin A.; Parrish, William R.; Rosas-Ballina, Mauricio; Ochani, Mahendar; Puerta, Margot; Ochani, Kanta; Chavan, Sangeeta; Al-Abed, Yousef; Tracey, Kevin J.

2015-01-01

The excessive release of cytokines by the immune system contributes importantly to the pathogenesis of inflammatory diseases. Recent advances in understanding the biology of cytokine toxicity led to the discovery of the “cholinergic anti-inflammatory pathway,” defined as neural signals transmitted via the vagus nerve that inhibit cytokine release through a mechanism that requires the alpha7 subunit-containing nicotinic acetylcholine receptor (α7nAChR). Vagus nerve regulation of peripheral functions is controlled by brain nuclei and neural networks, but despite considerable importance, little is known about the molecular basis for central regulation of the vagus nerve-based cholinergic anti-inflammatory pathway. Here we report that brain acetylcholinesterase activity controls systemic and organ specific TNF production during endotoxemia. Peripheral administration of the acetylcholinesterase inhibitor galantamine significantly reduced serum TNF levels through vagus nerve signaling, and protected against lethality during murine endotoxemia. Administration of a centrally-acting muscarinic receptor antagonist abolished the suppression of TNF by galantamine, indicating that suppressing acetylcholinesterase activity, coupled with central muscarinic receptors, controls peripheral cytokine responses. Administration of galantamine to α7nAChR knockout mice failed to suppress TNF levels, indicating that the α7nAChR-mediated cholinergic anti-inflammatory pathway is required for the anti-inflammatory effect of galantamine. These findings show that inhibition of brain acetylcholinesterase suppresses systemic inflammation through a central muscarinic receptor-mediated and vagal- and α7nAChR-dependent mechanism. Our data also indicate that a clinically used centrally-acting acetylcholinesterase inhibitor can be utilized to suppress abnormal inflammation to therapeutic advantage. PMID:18639629

Acetylcholinesterase inhibitors rapidly activate Trk neurotrophin receptors in the mouse hippocampus

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Autio, Henri; Mätlik, Kert; Rantamäki, Tomi; Lindemann, Lothar; Hoener, Marius C; Chao, Moses; Arumäe, Urmas; Castrén, Eero

2014-01-01

Acetylcholinesterase inhibitors are first-line therapies for Alzheimer's disease. These drugs increase cholinergic tone in the target areas of the cholinergic neurons of the basal forebrain. Basal forebrain cholinergic neurons are dependent upon trophic support by nerve growth factor (NGF) through its neurotrophin receptor, TrkA. In the present study, we investigated whether the acetylcholinesterase inhibitors donepezil and galantamine could influence neurotrophin receptor signaling in the brain. Acute administration of donepezil (3 mg/kg, i.p.) led to the rapid autophosphorylation of TrkA and TrkB neurotrophin receptors in the adult mouse hippocampus. Similarly, galantamine dose-dependently (3, 9 mg/kg, i.p.) increased TrkA and TrkB phosphorylation in the mouse hippocampus. Both treatments also increased the phosphorylation of transcription factor CREB and tended to increase the phosphorylation of AKT kinase but did not alter the activity of MAPK42/44. Chronic treatment with galantamine (3 mg/kg, i.p., 14 days), did not induce changes in hippocampal NGF and BDNF synthesis or protein levels. Our findings show that acetylcholinesterase inhibitors are capable of rapidly activating hippocampal neurotrophin signaling and thus suggest that therapies targeting Trk signaling may already be in clinical use in the treatment of AD. PMID:21820453

Effects of Chlorophenoxy Herbicides and Their Main Transformation Products on DNA Damage and Acetylcholinesterase Activity

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Sofia Benfeito

2014-01-01

Full Text Available Persistent pesticide transformation products (TPs are increasingly being detected among different environmental compartments, including groundwater and surface water. However, there is no sufficient experimental data on their toxicological potential to assess the risk associated with TPs, even if their occurrence is known. In this study, the interaction of chlorophenoxy herbicides (MCPA, mecoprop, 2,4-D and dichlorprop and their main transformation products with calf thymus DNA by UV-visible absorption spectroscopy has been assessed. Additionally, the toxicity of the chlorophenoxy herbicides and TPs was also assessed evaluating the inhibition of acetylcholinesterase activity. On the basis of the results found, it seems that AChE is not the main target of chlorophenoxy herbicides and their TPs. However, the results found showed that the transformation products displayed a higher inhibitory activity when compared with the parent herbicides. The results obtained in the DNA interaction studies showed, in general, a slight effect on the stability of the double helix. However, the data found for 4-chloro-2-methyl-6-nitrophenol suggest that this transformation product can interact with DNA through a noncovalent mode.

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

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Stasiuk, Maria; Janiszewska, Alicja; Kozubek, Arkadiusz

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, showing a correlation with changes in the conformation of the enzyme tested by the intrinsic fluorescence of the Trp residues of the protein. PMID:24787269

Evaluation of cholinesterase inhibitory and antioxidant activities of wild and cultivated samples of sage (Salvia fruticosa) by activity-guided fractionation.

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Senol, Fatma Sezer; Orhan, Ilkay Erdogan; Erdem, Sinem Aslan; Kartal, Murat; Sener, Bilge; Kan, Yüksel; Celep, Ferhat; Kahraman, Ahmet; Dogan, Musa

2011-11-01

In European folk medicine, Salvia species have traditionally been used to enhance memory. In our previous study of 55 Salvia taxa, we explored significant anticholinesterase activity of cultivated S. fruticosa. In this study, we compared the inhibitory activity of dichloromethane, ethyl acetate, and ethanol extracts of 3 wild-grown samples and 1 cultivated sample of S. fruticosa against acetylcholinesterase and butyrylcholinesterase enzymes (which are associated with pathogenesis of Alzheimer's disease) by using the spectrophotometric Ellman method. Antioxidant activities were assessed by determining 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity, iron-chelating capacity, and ferric-reducing antioxidant power. The dichloromethane extract of the cultivated sample was then subjected to fractionation by using open column chromatography and medium-pressure liquid chromatography to obtain the most active fraction by activity-guided fractionation. All fractions and subfractions were tested in the same manner, and inactive subfractions were discarded. The essential oil of the cultivated sample was analyzed by gas chromatography-mass spectrometry.

Interleukin 6 modulates acetylcholinesterase activity of brain neurons

International Nuclear Information System (INIS)

Clarencon, D.; Multon, E.; Galonnier, M.; Estrade, M.; Fournier, C.; Mathieu, J.; Mestries, J.C.; Testylier, G.; Fatome, M.

1995-01-01

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)

Repetitive obidoxime treatment induced increase of red blood cell acetylcholinesterase activity even in a late phase of a severe methamidophos poisoning: A case report.

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Steinritz, Dirk; Eyer, Florian; Worek, Franz; Thiermann, Horst; John, Harald

2016-02-26

Accidental self-poisoning or deliberate use in suicidal intent of organophosphorus pesticides (OPP), which are widely used in agriculture, represent a health problem worldwide. Symptoms of poisoning are characterized by acute cholinergic crisis caused by inhibition of acetylcholinesterase. A 75-year-old male patient ingested 20ml of an OPP solution containing 10% methamidophos in suicidal intent. In the course of poisoning typical clinical symptoms of cholinergic crisis (miosis, bradycardia, hypotension, hypersalivation and impairment of neurologic status) were evident. Butyryl (plasma) cholinesterase (BChE) and red blood cell acetylcholinesterase (RBC-AChE) revealed decreased activities, thus specific treatment with the enzyme reactivator obidoxime was started. Inhibitory activity of the patient's plasma indicated significant amounts of persisting methamidophos in the circulation and was still found on day 4 after ingestion. Due to missing spontaneous breathing on day 6, obidoxime was administered again. Afterwards a significant increase of RBC-AChE activity was found. The patient was extubated on day 10 and a restitution ad integrum was achieved. In conclusion, obidoxime is a potent reactivator of OPP-inhibited AChE. A repetitive and prolonged administration of obidoxime should be considered in cases of severe methamidophos poisoning and should be tailored with an advanced analytical biomonitoring. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Methyl jasmonate enhances memory performance through inhibition of oxidative stress and acetylcholinesterase activity in mice.

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Eduviere, Anthony T; Umukoro, S; Aderibigbe, Adegbuyi O; Ajayi, Abayomi M; Adewole, Folashade A

2015-07-01

Current research effort focuses on the development of safer natural compounds with multipronged mechanisms of action that could be used to ameliorate memory deficits in patients with Alzheimer's disease, as cure for the disease still remains elusive. In this study, we evaluated the effect of methyl jasmonate (MJ), a naturally occurring bioactive compound on memory, acetylcholinesterase activity and biomarkers of oxidative stress in mice. Male Swiss mice were treated with intraperitoneal injection of MJ (10-40 mg/kg) alone or in combination with scopolamine (3mg/kg) once daily for 7 days. Thirty minutes after the last treatment, memory functions were assessed using Y-maze and object recognition tests. Thereafter, acetylcholinesterase activity and levels of biomarkers of oxidative stress were assessed in mice brains using standard biochemical procedures. MJ significantly enhanced memory performance and reversed scopolamine-induced cognitive impairment in mice. MJ demonstrated significant inhibition of acetylcholinesterase activity suggesting increased cholinergic neurotransmission. It further decreased malondialdehyde concentrations in mouse brain indicating antioxidant activity. Moreover, MJ significantly increased glutathione levels and activity of antioxidant enzymes (catalase and superoxide dismutase) in mice brains. The increased oxidative stress; evidenced by elevated levels of malondialdehyde and decreased antioxidant defense systems in scopolamine-treated mice was attenuated by MJ. The results of this study suggest that MJ may be useful in conditions associated with memory dysfunctions or age-related cognitive decline. The positive effect of MJ on memory may be related to inhibition of oxidative stress and enhancement of cholinergic neurotransmission through inhibition of acetylcholinesterase activity. Copyright © 2015 Elsevier Inc. All rights reserved.

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

International Nuclear Information System (INIS)

Mejri, Najoua

2007-01-01

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)

Micropropagation of Ficus religiosa L. via leaf explants and comparative evaluation of acetylcholinesterase inhibitory activity in the micropropagated and conventionally grown plants.

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Siwach, Priyanka; Gill, Anita Rani

2014-10-01

A high-frequency, season-independent, in vitro regeneration of Ficusreligiosa was developed, followed by comparative acetylcholinesterase inhibitory (AChEI) activity assay of the in vitro raised and conventionally grown plants. The use of AChEI activity is the most accepted strategy for the treatment of Alzheimer disease. Fully expanded, mature leaves were cut into different segments to initiate the cultures. The middle section of the leaf in vertical orientation with cut portion inserted inside the medium was found most suitable for direct shoot regeneration. Leaf explants responded with nearly consistent frequency (60-66.67 %) throughout the year. To obtain high frequency response with enhanced shoot multiplication rate, 32 plant growth regulator regimes were screened amongst which benzylaminopurine at 5.0 mg/l was found most suitable, yielding 100 % response and maximum number of shoots per explant (7.93); same concentration was also most supportive for repeated multiplication (6.53 shoots). The quality of the shoots and multiplication rate could be significantly enhanced (24.35 shoots) when adenine sulphate, glutamine and phloroglucinol, in an optimised concentration, were additionally supplemented. The clonal nature of the micropropagated plants was confirmed by random amplified polymorphic DNA analysis. A comparative analysis of AChEI activity was carried out amongst the methanolic extracts of stem segments of the mother plant, randomly selected seedlings of different age (4 and 6 months old) of the same mother plant and randomly selected micropropagated plants of different age (3 and 6 months age). The mother plant sample showed effective AChEI activity, with IC 50 of 66.46 μg/ml while seedlings, of different age groups, performed poorly (6-month-old seedlings, Se-1 6M , yielded IC 50 of 20,538.46 μg/ml, while two randomly selected 4 months' aged seedlings, Se-2 4M and Se-3 4M exhibited IC 50 of 19,341.03 and 24,281.70 μg/ml). On the other hand

Maytenus distichophylla and Salacia crassifolia: source of products with potential acetylcholinesterase inhibition

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Fernanda L. Ferreira

Full Text Available ABSTRACT The phytochemical study of the extract leaves from Maytenus distichophylla Mart. and Salacia crassifolia (Mart. ex Schult. G. Don, Celastraceae, resulted in the isolation of 3-oxofriedelane, 3β-hydroxyfriedelane, 3β,24-dihydroxyfriedelane, 3-oxo-28,29-dihydroxyfriedelane, two mixtures of pentacyclic triterpenes (α-amyrin with β-amyrin and 3β-stearyloxy-urs-12-ene with 3β-stearyloxy-olean-12-ene, 3β-palmityloxy-urs-12-ene, the steroid β-sitosterol and its glycosylated derivative β-glucosyl-β-sitosterol, tritriacontanoic acid and the natural polymer gutta percha. The chemical structures of these constituents were established by IR, 1H and 13C NMR spectral data. Crude extracts, the mixtures of triterpenes and the isolated constituents were subjected to in vitro acetylcholinesterase inhibitory evaluation. Acetylcholinesterase inhibitory effect was observed for crude chloroform extract leaves from M. distichophylla (100% and S. crassifolia (97.93 ± 5.63% and for the triterpenes 3β,24-dihydroxyfriedelane (99.05 ± 1.12%, 3-oxo-28,29-dihydroxyfriedelane (90.59 ± 3.76% and 3β-palmityloxy-urs-12-ene (97.93 ± 1.47%. The percent inhibitions induced by these natural products were very similar to those produced by physostigmine (93.94 ± 2.10% a standard acetylcholinesterase inhibitor. Therefore, these results open perspectives for the use of these species as source of compounds with similar physostigmine pharmacological effect.

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

International Nuclear Information System (INIS)

Kaushik, R.; Rosenfeld, Clint A.; Sultatos, L.G.

2007-01-01

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

In vitro screening for anti-cholinesterase and antioxidant activity of methanolic extracts of ayurvedic medicinal plants used for cognitive disorders.

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Maya Mathew

Full Text Available Inhibition of Acetylcholinesterase (AChE is still considered as the main therapeutic strategy against Alzheimer's disease (AD. Many plant derived phytochemicals have shown AChE inhibitory activity in addition to the currently approved drugs for AD. In the present study, methanolic extracts of 20 plants used in Indian Ayurvedic system of medicine for improving cognitive function were screened for acetylcholinesterase inhibitory activity by Ellman's microplate colorimetric method. Out of 20 extracts, Emblica officinalis, Nardostachys jatamansi, Nelumbo nucifera, Punica granatum and Raulfia Serpentina showed IC50 values <100 µg/ml for acetylcholinesterase inhibitory activity. Antioxidant activities of these plants were assessed by DPPH scavenging assay. Among the extracts used, antioxidant activity was highest for Terminalia chebula and Emblica officinalis with IC50 values <10 µg/ml. Considering the complex multifactorial etiology of AD, these plant extracts will be safer and better candidates for the future disease modifying therapies against this devastating disease.

In Vitro Screening for Anti-Cholinesterase and Antioxidant Activity of Methanolic Extracts of Ayurvedic Medicinal Plants Used for Cognitive Disorders

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Mathew, Maya; Subramanian, Sarada

2014-01-01

Inhibition of Acetylcholinesterase (AChE) is still considered as the main therapeutic strategy against Alzheimer’s disease (AD). Many plant derived phytochemicals have shown AChE inhibitory activity in addition to the currently approved drugs for AD. In the present study, methanolic extracts of 20 plants used in Indian Ayurvedic system of medicine for improving cognitive function were screened for acetylcholinesterase inhibitory activity by Ellman’s microplate colorimetric method. Out of 20 extracts, Emblica officinalis, Nardostachys jatamansi, Nelumbo nucifera, Punica granatum and Raulfia Serpentina showed IC50 values <100 µg/ml for acetylcholinesterase inhibitory activity. Antioxidant activities of these plants were assessed by DPPH scavenging assay. Among the extracts used, antioxidant activity was highest for Terminalia chebula and Emblica officinalis with IC50 values <10 µg/ml. Considering the complex multifactorial etiology of AD, these plant extracts will be safer and better candidates for the future disease modifying therapies against this devastating disease. PMID:24466247

Potential anti-cholinesterase and β-site amyloid precursor protein cleaving enzyme 1 inhibitory activities of cornuside and gallotannins from Cornus officinalis fruits.

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Bhakta, Himanshu Kumar; Park, Chan Hum; Yokozawa, Takako; Tanaka, Takashi; Jung, Hyun Ah; Choi, Jae Sue

2017-07-01

Cholinesterase (ChE) and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors are promising agents for the treatment of Alzheimer's disease (AD). In the present study, we examined the inhibitory activity of seven compounds isolated from the fruits of Cornus officinalis, cornuside, polymeric proanthocyanidins, 1,2,3-tri-O-galloyl-β-D-glucose, 1,2,3,6-tetra-O-galloyl-β-D-glucose, tellimagrandin I, tellimagrandin II, and isoterchebin, against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and BACE1. All of the compounds displayed concentration-dependent in vitro inhibitory activity toward the ChEs and BACE1. Among them, tellimagrandin II exhibited the best inhibitory activity toward ChEs, whereas the best BACE1 inhibitor was 1,2,3,6-tetra-O-galloyl-β-D-glucose. Isoterchebin and polymeric proanthocyanidins were also significant ChE inhibitors. The kinetic and docking studies demonstrated that all compounds interacted with both the catalytic active sites and the peripheral anionic sites of the ChEs and BACE1. Tellimagrandin II, isoterchebin, and the polymeric proanthocyanidins exhibited concentration-dependent inhibition of peroxynitrite-mediated protein tyrosine nitration. In conclusion, we identified significant ChE and BACE1 inhibitors from Corni Fructus that could have value as new multi-targeted compounds for anti-AD agents.

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

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Gülsen Tel

2016-01-01

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.

Hyperglycemia induces memory impairment linked to increased acetylcholinesterase activity in zebrafish (Danio rerio).

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Capiotti, Katiucia Marques; De Moraes, Daiani Almeida; Menezes, Fabiano Peres; Kist, Luiza Wilges; Bogo, Maurício Reis; Da Silva, Rosane Souza

2014-11-01

Diabetes mellitus, which causes hyperglycemia, affects the central nervous system and can impairs cognitive functions, such as memory. The aim of this study was to investigate the effects of hyperglycemia on memory as well as on the activity of acethylcholinesterase. Hyperglycemia was induced in adult zebrafish by immersion in glucose 111mM by 14 days. The animals were divided in 4 groups: control, glucose-treated, glucose-washout 7-days and glucose-washout 14-days. We evaluated the performance in inhibitory avoidance task and locomotor activity. We also determined acethylcholinesterase activity and gene expression from whole brain. In order to counteract the effect of hyperglycemia underlined by effects on acethylcholinesterase activity, we treated the animals with galantamine (0.05ng/g), an inhibitor of this enzyme. Also we evaluated the gene expression of insulin receptor and glucose transporter from zebrafish brain. The hyperglycemia promoted memory deficit in adult zebrafish, which can be explained by increased AChE activity. The ache mRNA levels from zebrafish brain were decrease in 111mM glucose group and returned to normal levels after 7 days of glucose withdrawal. Insulin receptors (insra-1, insra-2, insrb-1 and insrb-2) and glut-3 mRNA levels were not significantly changed. Our results also demonstrated that galantamine was able to reverse the memory deficit caused by hyperglycemia, demonstrating that these effects involve modulation of AChE activity. These data suggest that the memory impairment induced by hyperglycemia is underlined by the cholinergic dysfunction caused by the mechanisms involving the control of acetylcholinesterase function and gene expression. Copyright © 2014 Elsevier B.V. All rights reserved.

Acetylcholinesterase activity in seabirds affected by the Prestige oil spill on the Galician coast (Spain)

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Oropesa, Ana-Lourdes; Perez-Lopez, Marcos; Hernandez, David; Soler, Francisco [Toxicology Area, Faculty of Veterinary Science (UEX), Avda. de la Universidad s/n. 10071 Caceres (Spain); Garcia, Jesus-Pablo [Toxicology Area, National Centre of Environmental Health, Instituto de Salud Carlos III, Majadahonda, Madrid (Spain); Fidalgo, Luis-Eusebio; Lopez-Beceiro, Ana [Rof Codina Clinical Hospital, Faculty of Veterinary Science (USC), Estrada de Granxa s/n. 27003 Lugo (Spain)

2007-01-01

In November 2002, the tanker Prestige broke in two and sank at the bottom of the ocean spilling about 70,000 t of fuel oil, which reached the coast of Galicia. It was considered the largest spill in maritime history, greatly affecting marine and related avian species. The spilled fuel oil contained high concentrations of polycyclic aromatic hydrocarbons (PAHs). Many species were affected and were found dead, although ongoing research is still being carried out on the sublethal effects. In this sense, little is known about the action of PAHs on Cholinesterase activity in seabirds. Consequently, the purpose of this study was to provide more information on the neurotoxicity of fuel oil on the seabirds most affected by the Prestige accident: common guillemot, Atlantic puffin and razorbill. On the other hand, data on normal values of acetylcholinesterase (AChE) activity were obtained to supply non-exposed values in seabirds. The oil spill produced a clear inhibitory effect on brain AChE activity in common guillemot (16%, p {<=} 0.01) and razorbill (22%, p {<=} 0.01), but not in Atlantic puffin (4%). Physiological levels of brain AChE, expressed in nmol acetylcholine hydrolysed min{sup -} {sup 1} mg{sup -} {sup 1} protein were similar in non-exposed common guillemot (388.6 {+-} 95.0) and Atlantic puffin (474.0 {+-} 60.7), however, razorbill values were higher (644.6 {+-} 66.9). (author)

Anti-acetylcholinesterase activity and antioxidant properties of extracts and fractions of Carpolobia lutea.

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Nwidu, Lucky Legbosi; Elmorsy, Ekramy; Thornton, Jack; Wijamunige, Buddhika; Wijesekara, Anusha; Tarbox, Rebecca; Warren, Averil; Carter, Wayne Grant

2017-12-01

There is an unmet need to discover new treatments for Alzheimer's disease. This study determined the anti-acetylcholinesterase (AChE) activity, DPPH free radical scavenging and antioxidant properties of Carpolobia lutea G. Don (Polygalaceae). The objective of this study is to quantify C. lutea anti-AChE, DPPH free radical scavenging, and antioxidant activities and cell cytotoxicity. Plant stem, leaves and roots were subjected to sequential solvent extractions, and screened for anti-AChE activity across a concentration range of 0.02-200 μg/mL. Plant DPPH radical scavenging activity, reducing power, and total phenolic and flavonoid contents were determined, and cytotoxicity evaluated using human hepatocytes. Carpolobia lutea exhibited concentration-dependent anti-AChE activity. The most potent inhibitory activity for the stem was the crude ethanol extract and hexane stem fraction oil (IC 50  = 140 μg/mL); for the leaves, the chloroform leaf fraction (IC 50  = 60 μg/mL); and for roots, the methanol, ethyl acetate and aqueous root fractions (IC 50  = 0.3-3 μg/mL). Dose-dependent free radical scavenging activity and reducing power were observed with increasing stem, leaf or root concentration. Total phenolic contents were the highest in the stem: ∼632 mg gallic acid equivalents/g for a hexane stem fraction oil. Total flavonoid content was the highest in the leaves: ∼297 mg quercetin equivalents/g for a chloroform leaf fraction. At 1 μg/mL, only the crude ethanol extract oil was significantly cytotoxic to hepatocytes. Carpolobia lutea possesses anti-AChE activity and beneficial antioxidant capacity indicative of its potential development as a treatment of Alzheimer's and other diseases characterized by a cholinergic deficit.

Synthesis, DNA Cleavage Activity, Cytotoxicity, Acetylcholinesterase Inhibition, and Acute Murine Toxicity of Redox-Active Ruthenium(II) Polypyridyl Complexes.

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Alatrash, Nagham; Narh, Eugenia S; Yadav, Abhishek; Kim, Mahn-Jong; Janaratne, Thamara; Gabriel, James; MacDonnell, Frederick M

2017-07-06

Four mononuclear [(L-L) 2 Ru(tatpp)] 2+ and two dinuclear [(L-L) 2 Ru(tatpp)Ru(L-L) 2 ] 4+ ruthenium(II) polypyridyl complexes (RPCs) containing the 9,11,20,22-tetraazatetrapyrido[3,2-a:2',3'-c:3'',2''-l:2''',3'''-n]pentacene (tatpp) ligand were synthesized, in which L-L is a chelating diamine ligand such as 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 3,4,7,8-tetramethyl-1,10-phenanthroline (Me 4 phen) or 4,7-diphenyl-1,10-phenanthroline (Ph 2 phen). These Ru-tatpp analogues all undergo reduction reactions with modest reducing agents, such as glutathione (GSH), at pH 7. These, plus several structurally related but non-redox-active RPCs, were screened for DNA cleavage activity, cytotoxicity, acetylcholinesterase (AChE) inhibition, and acute mouse toxicity, and their activities were examined with respect to redox activity and lipophilicity. All of the redox-active RPCs show single-strand DNA cleavage in the presence of GSH, whereas none of the non-redox-active RPCs do. Low-micromolar cytotoxicity (IC 50 ) against malignant H358, CCL228, and MCF7 cultured cell lines was mainly restricted to the redox-active RPCs; however, they were substantially less toxic toward nonmalignant MCF10 cells. The IC 50 values for AChE inhibition in cell-free assays and the acute toxicity of RPCs in mice revealed that whereas most RPCs show potent inhibitory action against AChE (IC 50 values <15 μm), Ru-tatpp complexes as a class are surprisingly well tolerated in animals relative to other RPCs. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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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...

Toxicological effect of herbicides (diuron and bentazon) on snake venom and electric eel acetylcholinesterase.

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Ahmed, Mushtaq; Latif, Nadia; Khan, Rehmat Ali; Ahmad, Akhlaq

2012-08-01

The toxicological effects of the active ingredients of the herbicides diuron and bentazon on the activity of acetylcholinesterase (AChE) of krait (Bungarus sindanus) venom and electric eel (Electrophorus electricus) were studied. The diuron and entazon caused non-competitive inhibition of AChE from both species. For the venom AChE, the calculated IC50 for diuron and bentazon were found to be 3.25 and 0.14 μM, while for eel AChE, the respective IC50 values were 3.6 and 0.135 μM. In comparison, bentazon was a more potent inhibitor than diuron of AChE from both species. The insecticide lindane did not have any inhibitory effect on AChE activity in either species, even when tested at high concentrations (200-800 μM).

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

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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.

Effect of viologen-phosphorus dendrimers on acetylcholinesterase and butyrylcholinesterase activities.

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Ciepluch, Karol; Weber, Monika; Katir, Nadia; Caminade, Anne-Marie; El Kadib, Abdelkrim; Klajnert, Barbara; Majoral, Jean Pierre; Bryszewska, Maria

2013-03-01

The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is the first step in checking whether new compounds can be considered as drugs for treating neurodegenerative diseases. The effect of viologen-phosphorus dendrimers on AChE and BChE activities was studied. The results show that the effects on the cholinesterase activities depend on dendrimer type and size. Viologen dendrimers can interact with the enzymes in two ways: they can bind either to a peripheral site of the enzyme or to amino acids located near the active site, inhibiting catalysis by both cholinesterases. All tested non-toxic viologen-phosphorus dendrimers inhibited the activities of both cholinesterases, showing their potential as new drugs for treating neurodegenerative diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

Synthesis, enzyme inhibitory kinetics mechanism and computational study of N-(4-methoxyphenethyl-N-(substituted-4-methylbenzenesulfonamides as novel therapeutic agents for Alzheimer’s disease

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Muhammad Athar Abbasi

2018-06-01

Full Text Available The present study comprises the synthesis of a new series of sulfonamides derived from 4-methoxyphenethylamine (1. The synthesis was initiated by the reaction of 1 with 4-methylbenzenesulfonyl chloride (2 in aqueous sodium carbonate solution at pH 9 to yield N-(4-methoxyphenethyl-4-methylbenzensulfonamide (3.This parent molecule 3 was subsequently treated with various alkyl/aralkyl halides, (4a–j, using N,N-dimethylformamide (DMF as solvent and LiH as activator to produce a series of new N-(4-methoxyphenethyl-N-(substituted-4-methylbenzenesulfonamides (5a–j. The structural characterization of these derivatives was carried out by spectroscopic techniques like IR, 1H-NMR, and 13C-NMR. The elemental analysis data was also coherent with spectral data of these molecules. The inhibitory effects on acetylcholinesterase and DPPH were evaluated and it was observed that N-(4-Methoxyphenethyl-4-methyl-N-(2-propylbenzensulfonamide (5c showed acetylcholinesterase inhibitory activity 0.075 ± 0.001 (IC50 0.075 ± 0.001 µM comparable to Neostigmine methylsulfate (IC50 2.038 ± 0.039 µM.The docking studies of synthesized ligands 5a–j were also carried out against acetylcholinesterase (PDBID 4PQE to compare the binding affinities with IC50 values. The kinetic mechanism analyzed by Lineweaver-Burk plots demonstrated that compound (5c inhibits the acetylcholinesterase competitively to form an enzyme inhibitor complex. The inhibition constants Ki calculated from Dixon plots for compound (5c is 2.5 µM. It was also found from kinetic analysis that derivative 5c irreversible enzyme inhibitor complex. It is proposed on the basis of our investigation that title compound 5c may serve as lead structure for the design of more potent acetylcholinesterase inhibitors.

Phytochemical Characterization, Antibacterial, Acetylcholinesterase Inhibitory and Cytotoxic Properties of Cryptostephanus vansonii, an Endemic Amaryllid

Czech Academy of Sciences Publication Activity Database

Moyo, M.; Aremu, A.O.; Chukwujekwu, J. C.; Grúz, Jiří; Skořepa, Jiří; Doležal, Karel; Katsvanga, C. A. T.; Van Staden, J.

2017-01-01

Roč. 31, č. 5 (2017), s. 713-720 ISSN 0951-418X R&D Projects: GA MŠk(CZ) LO1204; GA MŠk LK21306 Institutional support: RVO:61389030 Keywords : in-vitro * alzheimers-disease * alkaloids * extracts * antioxidant * coumarins * apoptosis * phylogeny * medicine * bacteria * acetylcholinesterase inhibition * Amaryllidaceae * antibacterial * cytotoxicity * flavonoids * phenolic acids Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Plant sciences, botany Impact factor: 3.092, year: 2016

Crystal structure of snake venom acetylcholinesterase in complex with inhibitory antibody fragment Fab410 bound at the peripheral site: evidence for open and closed states of a back door channel.

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Bourne, Yves; Renault, Ludovic; Marchot, Pascale

2015-01-16

The acetylcholinesterase found in the venom of Bungarus fasciatus (BfAChE) is produced as a soluble, non-amphiphilic monomer with a canonical catalytic domain but a distinct C terminus compared with the other vertebrate enzymes. Moreover, the peripheral anionic site of BfAChE, a surface site located at the active site gorge entrance, bears two substitutions altering sensitivity to cationic inhibitors. Antibody Elec410, generated against Electrophorus electricus acetylcholinesterase (EeAChE), inhibits EeAChE and BfAChE by binding to their peripheral sites. However, both complexes retain significant residual catalytic activity, suggesting incomplete gorge occlusion by bound antibody and/or high frequency back door opening. To explore a novel acetylcholinesterase species, ascertain the molecular bases of inhibition by Elec410, and document the determinants and mechanisms for back door opening, we solved a 2.7-Å resolution crystal structure of natural BfAChE in complex with antibody fragment Fab410. Crystalline BfAChE forms the canonical dimer found in all acetylcholinesterase structures. Equally represented open and closed states of a back door channel, associated with alternate positions of a tyrosine phenol ring at the active site base, coexist in each subunit. At the BfAChE molecular surface, Fab410 is seated on the long Ω-loop between two N-glycan chains and partially occludes the gorge entrance, a position that fully reflects the available mutagenesis and biochemical data. Experimentally based flexible molecular docking supports a similar Fab410 binding mode onto the EeAChE antigen. These data document the molecular and dynamic peculiarities of BfAChE with high frequency back door opening, and the mode of action of Elec410 as one of the largest peptidic inhibitors targeting the acetylcholinesterase peripheral site. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Linarin Inhibits the Acetylcholinesterase Activity In-vitro and Ex-vivo

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Feng, Xinchi; Wang, Xin; Liu, Youping; Di, Xin

2015-01-01

Linarin is a flavone glycoside in the plants Flos chrysanthemi indici, Buddleja officinalis, Cirsium setosum, Mentha arvensis and Buddleja davidii, and has been reported to possess analgesic, antipyretic, anti-inflammatory and neuroprotective activities. In this paper, linarin was investigated for its AChE inhibitory potential both in-vitro and ex-vivo. Ellman’s colorimetric method was used for the determination of AChE inhibitory activity in mouse brain. In-vitro assays revealed that linarin inhibited AChE activity with an IC50 of 3.801 ± 1.149 μM. Ex-vivo study showed that the AChE activity was significantly reduced in both the cortex and hippocampus of mice treated intraperitoneally with various doses of linarin (35, 70 and 140 mg/Kg). The inhibition effects produced by high dose of linarin were the same as that obtained after huperzine A treatment (0.5 mg/Kg). Molecular docking study revealed that both 4’-methoxyl group and 7-O-sugar moiety of linarin played important roles in ligand-receptor binding and thus they are mainly responsible for AChE inhibitory activity. In view of its potent AChE inhibitory activity, linarin may be a promising therapeutic agent for the treatment of some diseases associated with AChE, such as glaucoma, myasthenia gravis, gastric motility and Alzheimer’s disease. PMID:26330885

Interleukin 6 modulates acetylcholinesterase activity of brain neurons; Effet de l`interleukine 6 sur l`activite de l`acetylcholinesterase des neurones centraux

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Clarencon, D.; Multon, E.; Galonnier, M.; Estrade, M.; Fournier, C.; Mathieu, J.; Mestries, J.C.; Testylier, G.; Fatome, M.

1995-12-31

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). 3 refs.

Acetylcholinesterase assay for cerebrospinal fluid using bupivacaine to inhibit butyrylcholinesterase

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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.

Curcumin administration suppress acetylcholinesterase gene expression in cadmium treated rats.

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Akinyemi, Ayodele Jacob; Oboh, Ganiyu; Fadaka, Adewale Oluwaseun; Olatunji, Babawale Peter; Akomolafe, Seun

2017-09-01

Curcumin, the main polyphenolic component of turmeric (Curcuma longa) rhizomes have been reported to exert anticholinesterase potential with limited information on how they regulate acetylcholinesterase (AChE) gene expression. Hence, this study sought to evaluate the effect of curcumin on cerebral cortex acetylcholinesterase (AChE) activity and their mRNA gene expression level in cadmium (Cd)-treated rats. Furthermore, in vitro effect of different concentrations of curcumin (1-5μg/mL) on rat cerebral cortex AChE activity was assessed. Animals were divided into six groups (n=6): group 1 serve as control (without Cd) and receive saline/vehicle, group 2 receive saline plus curcumin at 25mg/kg, group 3 receive saline plus curcumin 50mg/kg, group 4 receive Cd plus vehicle, group 5 receive Cd plus curcumin at 25mg/kg and group 6 receive Cd plus curcumin at 50mg/kg. Rats received Cd (2.5mg/kg) and curcumin (25 and 50mg/kg, respectively) by oral gavage for 7days. Acetylcholinesterase activity was measured by Ellman's method and AChE expression was carried out by a quantitative reverse transcriptase polymerase chain reaction (RT-qPCR) assay. We observed that acute administration of Cd increased acetylcholinesterase activity and in addition caused a significant (Pcurcumin inhibited AChE activity and alters AChE mRNA levels when compared to Cd-treated group. In addition, curcumin inhibits rat cerebral cortex AChE activity in vitro. In conclusion, curcumin exhibit anti-acetylcholinesterase activity and suppressed AChE mRNA gene expression level in Cd exposed rats, thus providing some biochemical and molecular evidence on the therapeutic effect of this turmeric-derived compound in treating neurological disorders including Alzheimer's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of acetylcholinesterase-inhibition by itopride.

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Iwanaga, Y; Kimura, T; Miyashita, N; Morikawa, K; Nagata, O; Itoh, Z; Kondo, Y

1994-11-01

Itopride is a gastroprokinetic benzamide derivative. This agent inhibited both electric eel acetylcholinesterase (AChE) and horse serum butyrylcholinesterase (BuChE). The IC50 of itopride with AChE (2.04 +/- 0.27 microM) was, however, 100-fold less than that with BuChE, whereas in the case of neostigmine with AChE (11.3 +/- 3.4 nM), it was 10-fold less. The recovery of AChE activity inhibited by 10(-7) M neostigmine was partial, but that inhibited by up to 3 x 10(-5) M itopride was complete when the reaction mixture was subjected to ultrafiltration. Double reciprocal plots of the experimental data showed that both Km and Vmax were affected by itopride, suggesting that the inhibition is a "mixed" type, although primarily being an uncompetitive one. The inhibitory effect of itopride on cholinesterase (ChE) activity in guinea pig gastrointestine was much weaker than that on pure AChE. However, in the presence of a low dose of diisopropyl fluorophosphate, just enough to inhibit BuChE but not AChE, the IC50s of itopride against ChE activities were found to be about 0.5 microM. In conclusion, itopride exerts reversible and a "mixed" type of inhibition preferably against AChE. The IC50 of itopride for electric eel and guinea pig gastrointestinal AChE inhibition was 200 times and 50 times as large as that of neostigmine, respectively.

Acotiamide hydrochloride (Z-338) enhances gastric motility and emptying by inhibiting acetylcholinesterase activity in rats.

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Kawachi, Masanao; Matsunaga, Yugo; Tanaka, Takao; Hori, Yuko; Ito, Katsunori; Nagahama, Kenji; Ozaki, Tomoko; Inoue, Naonori; Toda, Ryoko; Yoshii, Kazuyoshi; Hirayama, Masamichi; Kawabata, Yoshihiro; Takei, Mineo

2011-09-01

In clinical trials, acotiamide hydrochloride (acotiamide: Z-338) has been reported to be useful in the treatment of functional dyspepsia. Here, we investigated the effects of acotiamide on gastric contraction and emptying activities in rats in comparison with itopride hydrochloride (itopride) and mosapride citrate (mosapride). We also examined in vitro the compound's inhibitory effect on acetylcholinesterase (AChE) activity derived from rat stomach. In in vivo studies, acotiamide (30 and 100mg/kg s.c.) and itopride (100mg/kg s.c.) markedly enhanced normal gastric antral motility in rats. In gastric motility dysfunction models, acotiamide (100mg/kg s.c.) and itopride (100mg/kg s.c.) improved both gastric antral hypomotility and the delayed gastric emptying induced by clonidine, an α(2)-adrenoceptor agonist. In contrast, mosapride (10mg/kg s.c.) had no effect on these models. Like the AChE inhibitors itopride (30 mg/kg s.c.) and neostigmine (10 μg/kg s.c.), acotiamide (10mg/kg s.c.) also clearly enhanced gastric body contractions induced by electrical stimulation of the vagus, which were abolished by atropine and hexamethonium, whereas mosapride (3 and 10mg/kg s.c.) did not. In in vitro studies, acotiamide concentration-dependently inhibited rat stomach-derived AChE activity (IC(50)=2.3 μmol/l). In addition, stomach tissue concentrations of acotiamide after administration at 10mg/kg s.c. were sufficient to produce inhibition of AChE activity in rat stomach. These results suggest that acotiamide stimulates gastric motility and improves gastric motility dysfunction in rats by inhibiting AChE activity, and may suggest a role for acotiamide in improving gastric motility dysfunction in patients with functional dyspepsia. Copyright © 2011 Elsevier B.V. All rights reserved.

The Effect of Parathion on Red Blood Cell Acetylcholinesterase in the Wistar Rat

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Naofumi Bunya

2016-01-01

Full Text Available Organophosphorus (OP pesticide poisoning is a significant problem worldwide. Research into new antidotes for these acetylcholinesterase inhibitors, and even optimal doses for current therapies, is hindered by a lack of standardized animal models. In this study, we sought to characterize the effects of the OP pesticide parathion on acetylcholinesterase in a Wistar rat model that included comprehensive medical care. Methods. Male Wistar rats were intubated and mechanically ventilated and then poisoned with between 20 mg/kg and 60 mg/kg of intravenous parathion. Upon developing signs of poisoning, the rats were treated with standard critical care, including atropine, pralidoxime chloride, and midazolam, for up to 48 hours. Acetylcholinesterase activity was determined serially for up to 8 days after poisoning. Results. At all doses of parathion, maximal depression of acetylcholinesterase occurred at 3 hours after poisoning. Acetylcholinesterase recovered to nearly 50% of baseline activity by day 4 in the 20 mg/kg cohort and by day 5 in the 40 and 60 mg/kg cohorts. At day 8, most rats’ acetylcholinesterase had recovered to roughly 70% of baseline. These data should be useful in developing rodent models of acute OP pesticide poisoning.

Effect of fluorocarbons on acetylcholinesterase activity and some counter measures

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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.

Population activity structure of excitatory and inhibitory neurons.

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Bittner, Sean R; Williamson, Ryan C; Snyder, Adam C; Litwin-Kumar, Ashok; Doiron, Brent; Chase, Steven M; Smith, Matthew A; Yu, Byron M

2017-01-01

Many studies use population analysis approaches, such as dimensionality reduction, to characterize the activity of large groups of neurons. To date, these methods have treated each neuron equally, without taking into account whether neurons are excitatory or inhibitory. We studied population activity structure as a function of neuron type by applying factor analysis to spontaneous activity from spiking networks with balanced excitation and inhibition. Throughout the study, we characterized population activity structure by measuring its dimensionality and the percentage of overall activity variance that is shared among neurons. First, by sampling only excitatory or only inhibitory neurons, we found that the activity structures of these two populations in balanced networks are measurably different. We also found that the population activity structure is dependent on the ratio of excitatory to inhibitory neurons sampled. Finally we classified neurons from extracellular recordings in the primary visual cortex of anesthetized macaques as putative excitatory or inhibitory using waveform classification, and found similarities with the neuron type-specific population activity structure of a balanced network with excitatory clustering. These results imply that knowledge of neuron type is important, and allows for stronger statistical tests, when interpreting population activity structure.

Population activity structure of excitatory and inhibitory neurons.

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Sean R Bittner

Full Text Available Many studies use population analysis approaches, such as dimensionality reduction, to characterize the activity of large groups of neurons. To date, these methods have treated each neuron equally, without taking into account whether neurons are excitatory or inhibitory. We studied population activity structure as a function of neuron type by applying factor analysis to spontaneous activity from spiking networks with balanced excitation and inhibition. Throughout the study, we characterized population activity structure by measuring its dimensionality and the percentage of overall activity variance that is shared among neurons. First, by sampling only excitatory or only inhibitory neurons, we found that the activity structures of these two populations in balanced networks are measurably different. We also found that the population activity structure is dependent on the ratio of excitatory to inhibitory neurons sampled. Finally we classified neurons from extracellular recordings in the primary visual cortex of anesthetized macaques as putative excitatory or inhibitory using waveform classification, and found similarities with the neuron type-specific population activity structure of a balanced network with excitatory clustering. These results imply that knowledge of neuron type is important, and allows for stronger statistical tests, when interpreting population activity structure.

Population activity structure of excitatory and inhibitory neurons

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Doiron, Brent

2017-01-01

Many studies use population analysis approaches, such as dimensionality reduction, to characterize the activity of large groups of neurons. To date, these methods have treated each neuron equally, without taking into account whether neurons are excitatory or inhibitory. We studied population activity structure as a function of neuron type by applying factor analysis to spontaneous activity from spiking networks with balanced excitation and inhibition. Throughout the study, we characterized population activity structure by measuring its dimensionality and the percentage of overall activity variance that is shared among neurons. First, by sampling only excitatory or only inhibitory neurons, we found that the activity structures of these two populations in balanced networks are measurably different. We also found that the population activity structure is dependent on the ratio of excitatory to inhibitory neurons sampled. Finally we classified neurons from extracellular recordings in the primary visual cortex of anesthetized macaques as putative excitatory or inhibitory using waveform classification, and found similarities with the neuron type-specific population activity structure of a balanced network with excitatory clustering. These results imply that knowledge of neuron type is important, and allows for stronger statistical tests, when interpreting population activity structure. PMID:28817581

Global loss of acetylcholinesterase activity with mitochondrial complexes inhibition and inflammation in brain of hypercholesterolemic mice.

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Paul, Rajib; Borah, Anupom

2017-12-20

There exists an intricate relationship between hypercholesterolemia (elevated plasma cholesterol) and brain functions. The present study aims to understand the impact of hypercholesterolemia on pathological consequences in mouse brain. A chronic mouse model of hypercholesterolemia was induced by giving high-cholesterol diet for 12 weeks. The hypercholesterolemic mice developed cognitive impairment as evident from object recognition memory test. Cholesterol accumulation was observed in four discrete brain regions, such as cortex, striatum, hippocampus and substantia nigra along with significantly damaged blood-brain barrier by hypercholesterolemia. The crucial finding is the loss of acetylcholinesterase activity with mitochondrial dysfunction globally in the brain of hypercholesterolemic mice, which is related to the levels of cholesterol. Moreover, the levels of hydroxyl radical were elevated in the regions of brain where the activity of mitochondrial complexes was found to be reduced. Intriguingly, elevations of inflammatory stress markers in the cholesterol-rich brain regions were observed. As cognitive impairment, diminished brain acetylcholinesterase activity, mitochondrial dysfunctions, and inflammation are the prima facie pathologies of neurodegenerative diseases, the findings impose hypercholesterolemia as potential risk factor towards brain dysfunction.

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

International Nuclear Information System (INIS)

Yang Dongren; Howard, Angela; Bruun, Donald; Ajua-Alemanj, Mispa; Pickart, Cecile; Lein, Pamela J.

2008-01-01

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

Flavonoids, Antioxidant Potential, and Acetylcholinesterase Inhibition Activity of the Extracts from the Gametophyte and Archegoniophore of Marchantia polymorpha L.

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Xin Wang

2016-03-01

Full Text Available Marchantia polymorpha L. is a representative bryophyte used as a traditional Chinese medicinal herb for scald and pneumonia. The phytochemicals in M. polymorpha L. are terpenoids and flavonoids, among which especially the flavonoids show significant human health benefits. Many researches on the gametophyte of M. polymorpha L. have been reported. However, as the reproductive organ of M. polymorpha L., the bioactivity and flavonoids profile of the archegoniophore have not been reported, so in this work the flavonoid profiles, antioxidant and acetylcholinesterase inhibition activities of the extracts from the archegoniophore and gametophyte of M. polymorpha L. were compared by radical scavenging assay methods (DPPH, ABTS, O2−, reducing power assay, acetylcholinesterase inhibition assay and LC-MS analysis. The results showed that the total flavonoids content in the archegoniophore was about 10-time higher than that of the gametophyte. Differences between the archegoniophore and gametophyte of M. polymorpha L. were observed by LC-MS analysis. The archegoniophore extracts showed stronger bio-activities than those of the gametophyte. The archegoniophore extract showed a significant acetylcholinesterase inhibition, while the gametophyte extract hardly inhibited it.

Recruitment of activation receptors at inhibitory NK cell immune synapses.

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Nicolas Schleinitz

2008-09-01

Full Text Available Natural killer (NK cell activation receptors accumulate by an actin-dependent process at cytotoxic immune synapses where they provide synergistic signals that trigger NK cell effector functions. In contrast, NK cell inhibitory receptors, including members of the MHC class I-specific killer cell Ig-like receptor (KIR family, accumulate at inhibitory immune synapses, block actin dynamics, and prevent actin-dependent phosphorylation of activation receptors. Therefore, one would predict inhibition of actin-dependent accumulation of activation receptors when inhibitory receptors are engaged. By confocal imaging of primary human NK cells in contact with target cells expressing physiological ligands of NK cell receptors, we show here that this prediction is incorrect. Target cells included a human cell line and transfected Drosophila insect cells that expressed ligands of NK cell activation receptors in combination with an MHC class I ligand of inhibitory KIR. The two NK cell activation receptors CD2 and 2B4 accumulated and co-localized with KIR at inhibitory immune synapses. In fact, KIR promoted CD2 and 2B4 clustering, as CD2 and 2B4 accumulated more efficiently at inhibitory synapses. In contrast, accumulation of KIR and of activation receptors at inhibitory synapses correlated with reduced density of the integrin LFA-1. These results imply that inhibitory KIR does not prevent CD2 and 2B4 signaling by blocking their accumulation at NK cell immune synapses, but by blocking their ability to signal within inhibitory synapses.

Effects of endosulfan on brain acetylcholinesterase activity in juvenile bluegill sunfish

International Nuclear Information System (INIS)

Dutta, Hiran M.; Arends, Dane A.

2003-01-01

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

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

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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

Research Advances and Detection Methodologies for Microbe-Derived Acetylcholinesterase Inhibitors: A Systemic Review

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Jingqian Su

2017-01-01

Full Text Available Acetylcholinesterase inhibitors (AChEIs are an attractive research subject owing to their potential applications in the treatment of neurodegenerative diseases. Fungi and bacteria are major producers of AChEIs. Their active ingredients of fermentation products include alkaloids, terpenoids, phenylpropanoids, and steroids. A variety of in vitro acetylcholinesterase inhibitor assays have been developed and used to measure the activity of acetylcholinesterases, including modified Ellman’s method, thin layer chromatography bioautography, and the combined liquid chromatography-mass spectrometry/modified Ellman’s method. In this review, we provide an overview of the different detection methodologies, the microbe-derived AChEIs, and their producing strains.

Avaliação da inibição da acetilcolinesterase por extratos de plantas medicinais Evaluation of acetylcholinesterase inhibition by extracts from medicinal plants

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W.M. Mota

2012-01-01

Full Text Available Neste trabalho foi avaliada a atividade inibitória da acetilcolinesterase (AChE pelo método de Ellman, modificado por Rhee, de extratos aquosos e etanólicos de oito plantas utilizadas na medicina popular da região Nordeste do Brasil. O extrato aquoso de E. velutina não apresentou atividade inibitória enquanto o extrato aquoso de Maytenus rigida apresentou baixa atividade inibitória (percentual de inibição de 4%. Detectou-se atividade inibitória moderada com o extrato aquoso de P. piperoides (percentual de inibição de 40 %, enquanto o extrato de V. agnus-castus L. inibiu 74% da atividade da AChE, caracterizando-se como potente atividade inibitória. A avaliação da inibição da AChE com os extratos etanólicos demonstrou que os extratos de Sideroxylon obtusifolium, Erythrina velutina, Vitex agnus-castus, Phoradendron piperoides, Chrysobalanus icaco, Bauhinia cheilantha e Orbignya phalerata não apresentaram atividade inibitória. Baixa atividade inibitória foi observada com os extratos etanólicos de Maytenus rigida (percentual de inibição de 7% e de Hyptis fruticosa (percentual de inibição de 11%. O extrato etanólico de Moringa oleifera apresentou atividade inibitória moderada, inibindo 47% da atividade dessa enzima. Nenhum dos extratos etanólicos testados apresentou atividade inibitória potente da AChE. Os resultados dos estudos de inibição da acetilcolinesterase permitem concluir que o extrato aquoso de V. agnus-castus L. mostrou-se o mais eficaz quanto a inibição da AChE. Este resultado reforça a necessidade da continuidade do estudo desse extrato, de forma a realizar a partição do extrato e a purificação das frações para isolar a molécula responsável pela inibição observada.In this study, we evaluated the inhibitory activity against acetylcholinesterase (AChE according to Ellman's method, modified by Rhee, for ethanol and aqueous extracts from eight plants used in folk medicine in the northeast region of

Acetylcholinesterase inhibition and antibacterial activity of Mondia whitei adventitious roots and ex vitro-grown somatic embryogenic-biomass

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Ponnusamy Baskaran

2016-10-01

Full Text Available Mondia whitei (Hook.f. Skeels is an important endangered medicinal and commercial plant in South Africa. In vitro propagation systems are required for biomass production and bioactivity analysis to supplement wild resources/stocks. Adventitious roots from somatic embryogenic explants using suspension culture and ex vitro-grown plants produced via somatic embryogenesis were established using different plant growth regulator treatments. The adventitious root biomass and different parts of ex vitro-grown and mother plants were used to investigate the potential for acetylcholinesterase (AChE and antibacterial activities. Adventitious roots derived from 2.5 µM indole-3-acetic acid (IAA treatments and ex vitro-grown plants derived from meta-topolin riboside (mTR and IAA treatments gave the best AChE and antibacterial activities. The in vitro-established M. whitei and ex vitro biomass have comparable ability to function as inhibitors of acetylcholinesterase and antibacterial agents, and can be used as potent bioresources in traditional medicine

Enzyme inhibitory activity of selected Philippine plants

International Nuclear Information System (INIS)

Sasotona, Joseph S.; Hernandez, Christine C.

2015-01-01

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)

Fumigant toxicity and acetylcholinesterase inhibitory activity of 4 Asteraceae plant essential oils and their constituents against Japanese termite (Reticulitermes speratus Kolbe).

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Seo, Seon-Mi; Kim, Junheon; Kang, Jaesoon; Koh, Sang-Hyun; Ahn, Young-Joon; Kang, Kyu-Suk; Park, Il-Kwon

2014-07-01

This study investigated the fumigant toxicity of 4 Asteraceae plant essential oils and their constituents against the Japanese termite Reticulitermes speratus Kolbe. Fumigant toxicity varied with plant essential oils or constituents, exposure time, and concentration. Among the tested essential oils, those from Chamaemelum nobile exhibited the strongest fumigant toxicity, followed by those from Santolina chamaecyparissus, Ormenis multicaulis, and Eriocephalus punctulatus at 2 days after treatment. In all, 15, 24, 19, and 9 compounds were identified in the essential oils from C. nobile, E. punctulatus, O. multicaulis, and S. chamaecyparissus, respectively, by using gas chromatography, gas chromatography-mass spectrometry, or open-column chromatography. The identified compounds were tested individually for their fumigant toxicity against Japanese termites. Among the test compounds, trans-pinocarveol, caryophyllene oxide, sabinene hydrate, and santolina alcohol showed strong fumigant toxicity against Japanese termites. Acetylcholinesterase (AChE) inhibition activity of the identified compounds from C. nobile, E. punctulatus, O. multicaulis, and S. chamaecyparissus essential oils were tested to determine the mode of their action. The IC50 values of (+)-α-pinene, (-)-limonene, (-)-α-pinene, β-pinene, and β-phellandrene against Japanese termite AChE were 0.03, 0.13, 0.41, 0.42, and 0.67mg/mL, respectively. Further studies are warranted to determine the potential of these essential oils and their constituents as fumigants for termite control. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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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.

Investigating the Antioxidant and Acetylcholinesterase Inhibition Activities of Gossypium herbaceam

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Haji Akber Aisa

2013-01-01

Full Text Available Our previous research showed that standardized extract from the flowers of the Gossypium herbaceam labeled GHE had been used in clinical trials for its beneficial effects on brain functions, particularly in connection with age-related dementia and Alzheimer’s disease (AD. The aim of this work was to determine the components of this herb and the individual constituents of GHE. In order to better understand this herb for AD treatment, we investigated the acetylcholinesterase (AChE inhibition and antioxidant activity of GHE as well as the protective effects to PC12 cells against cytotoxicity induced by tertiary butyl hydroperoxide (tBHP using in vitro assays. The antioxidant activities were assessed by measuring their capabilities for scavenging 1,1-diphenyl-2-picylhydrazyl (DPPH and 2-2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS free radical as well as in inhibiting lipid peroxidation. Our data showed that GHE exhibited certain activities against AChE and also is an efficient free radical scavenger, which may be helpful in preventing or alleviating patients suffering from AD.

Acetylcholinesterase inhibitory activity of pyrrolizidine alkaloids from Echium confusum Coincy.

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Benamar, Houari; Tomassini, Lamberto; Venditti, Alessandro; Marouf, Abderrazak; Bennaceur, Malika; Serafini, Mauro; Nicoletti, Marcello

2017-06-01

Four pyrrolizidine alkaloids, namely 7-O-angeloyllycopsamine N-oxide 1, echimidine N-oxide 2, echimidine 3 and 7-O-angeloylretronecine 4, were isolated for the first time from the whole plant ethanolic extract of Echium confusum Coincy, through bioassay-guided approach. Their structures were determined by spectroscopic means. All the isolates compounds showed moderate activities in inhibiting AChE, with IC50 0.276-0.769.

Enzymatic and biochemical characterization of Bungarus sindanus snake venom acetylcholinesterase

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M Ahmed

2012-01-01

Full Text Available This study analyses venom from the elapid krait snake Bungarus sindanus, which contains a high level of acetylcholinesterase (AChE activity. The enzyme showed optimum activity at alkaline pH (8.5 and 45ºC. Krait venom AChE was inhibited by substrate. Inhibition was significantly reduced by using a high ionic strength buffer; low ionic strength buffer (10 mM PO4 pH 7.5 inhibited the enzyme by 1. 5mM AcSCh, while high ionic strength buffer (62 mM PO4 pH 7.5 inhibited it by 1 mM AcSCh. Venom acetylcholinesterase was also found to be thermally stable at 45ºC; it only lost 5% of its activity after incubation at 45ºC for 40 minutes. The Michaelis-Menten constant (Km for acetylthiocholine iodide hydrolysis was found to be 0.068 mM. Krait venom acetylcholinesterase was also inhibited by ZnCl2, CdCl2, and HgCl2 in a concentrationdependent manner. Due to the elevated levels of AChE with high catalytic activity and because it is more stable than any other sources, Bungarus sindanus venom is highly valuable for biochemical studies of this enzyme.

Intrinsically-generated fluctuating activity in excitatory-inhibitory networks

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Mastrogiuseppe, Francesca; Ostojic, Srdjan

2017-01-01

Recurrent networks of non-linear units display a variety of dynamical regimes depending on the structure of their synaptic connectivity. A particularly remarkable phenomenon is the appearance of strongly fluctuating, chaotic activity in networks of deterministic, but randomly connected rate units. How this type of intrinsically generated fluctuations appears in more realistic networks of spiking neurons has been a long standing question. To ease the comparison between rate and spiking networks, recent works investigated the dynamical regimes of randomly-connected rate networks with segregated excitatory and inhibitory populations, and firing rates constrained to be positive. These works derived general dynamical mean field (DMF) equations describing the fluctuating dynamics, but solved these equations only in the case of purely inhibitory networks. Using a simplified excitatory-inhibitory architecture in which DMF equations are more easily tractable, here we show that the presence of excitation qualitatively modifies the fluctuating activity compared to purely inhibitory networks. In presence of excitation, intrinsically generated fluctuations induce a strong increase in mean firing rates, a phenomenon that is much weaker in purely inhibitory networks. Excitation moreover induces two different fluctuating regimes: for moderate overall coupling, recurrent inhibition is sufficient to stabilize fluctuations; for strong coupling, firing rates are stabilized solely by the upper bound imposed on activity, even if inhibition is stronger than excitation. These results extend to more general network architectures, and to rate networks receiving noisy inputs mimicking spiking activity. Finally, we show that signatures of the second dynamical regime appear in networks of integrate-and-fire neurons. PMID:28437436

Molecular interaction studies of acetylcholinesterase with potential acetylcholinesterase inhibitors from the root of Rhodiola crenulata using molecular docking and isothermal titration calorimetry methods.

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Li, Fa-Jie; Liu, Yuan; Yuan, Yuan; Yang, Bin; Liu, Zhen-Ming; Huang, Lu-Qi

2017-11-01

(-)-Epicatechin gallate ((-)-ECG), 1,2,3,4,6-O-pentagalloylglucose (PGG), rhodionin, herbacetin and rhodiosin isolated from the root of Rhodiola crenulata exhibited potent, dose-dependent inhibitory effects on acetylcholinesterase (AChE) with IC 50 ranged from 57.50±5.83 to 2.43±0.34μg/mL. With the aim of explaining the differences in activity of these active ingredients and clarifying how they inhibit AChE, the AChE-inhibitor interactions were further explored using molecular docking and isothermal titration calorimetry (ITC) methods in the present study. Molecular docking studies revealed that all compounds except PGG showed binding energy values ranging from -10.30 to -8.00kcal/mol while the binding energy of galantamine, a known AChE inhibitor, was -9.53kcal/mol; they inhibited the AChE by binding into the ligand pocket with the similar binding pattern to that of galantamine by interacting with Glu199 of AChE. Inhibition constant of these active ingredients had a positive correlation with binding energy. The interaction between AChE and PGG was further evaluated with the ITC method and the results indicated that the PGG-AChE interaction was relevant to AChE concentration. The results revealed a possible mechanism for the AChE inhibition activity of these bioactive ingredients, which may provide some help in lead compounds optimization in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

In vitro antioxidant assessment and a rapid HPTLC bioautographic method for the detection of anticholinesterase inhibitory activity of Geophila repens

Institute of Scientific and Technical Information of China (English)

Umesh Chandra Dash; Atish Kumar Sahoo

2017-01-01

OBJECTIVE:Geophila repens (L.) I.M.Johnst.(Rubiaceae),a small,creeping,perennial herb,is claimed to have memory-enhancing property.The goal of this study was to assess its antioxidant and anticholinesterase activity and conduct a rapid bioautographic enzyme assay for screening acetylcholinesterase (ACHE) and butyrylcholinesterase (BChE) inhibition of G.repens extracts.METHODS:Antioxidant activity of G.repens extracts was assessed by performing 1,1-diphenyl-2-picrylhydrazyl (DPPH),nitric oxide (NO),superoxide (SOD),hydroxyl (OH) and total antioxidant capacity (TAC) assays.Anticholinesterase activity was investigated by quantifying the AChE and BChE inhibitory activities of chloroform (CGR),ethyl acetate (EGR) and methanol (MGR) extract fractions from G.repens leaves.A rapid high-performance thin-layer chromatography (HPTLC) bioautographic method for the detection of AChE and BChE inhibition was performed.RESULTS:Among all extract fractions,EGR exhibited the highest half maximal inhibitory concentration (IC50) in DPPH,SOD,NO,OH and TAC assays,with IC50 of (38.33 ± 3.21),(45.14 ± 1.78),(59.81 ± 1.32),(39.45 ± 0.79) and (43.76 ± 0.81) μg/mL respectively.EGR displayed competitive,reversible inhibition of AChE and BChE activities with IC50 of (68.63 ± 0.45) and (59.45 ± 0.45) μg/mL,respectively.Total phenolic and flavonoids contents of EGR were found to be 360.42 mg gallic acid equivalents and 257.31 mg quercetin equivalents per gram of extract.Phytoconstituents of the EGR extract that were inhibitors of cholinesterase produced white spots on the yellow background of HPTLC plates in the bioautographic test.CONCLUSION:The results of this study revealed that phenols and flavonoids could be responsible for the antioxidant,anticholinesterase activities of G.repens.

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

International Nuclear Information System (INIS)

Ballesteros, M.L.; Durando, P.E.; Nores, M.L.; Diaz, M.P.; Bistoni, M.A.; Wunderlin, D.A.

2009-01-01

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.

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

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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.

COMPARATIVE EVALUATION OF INHIBITORY ACTIVITY OF ...

African Journals Online (AJOL)

Osondu

2013-02-26

Feb 26, 2013 ... especially the four bacteria isolates used in this study are present in the epiphgram of both normal and ... Keyword: Albino snail, Archachatina marginata, Inhibitory activity, Epiphgram, Bacteria isolate. Introduction .... evolution.

Acetylcholinesterase inhibition by somes promising Brazilian medicinal plants.

Science.gov (United States)

Feitosa, C M; Freitas, R M; Luz, N N N; Bezerra, M Z B; Trevisan, M T S

2011-08-01

A microplate assay and a thin-layer chromatography (TLC) "in situ" assay based on the Ellman assay was used to screen for acetylcholinesterase inhibitors from ethyl acetate and methanol extracts of Brazilian medicinal plants of families that, according to the literature, have traditional uses that might be connected with acetylcholinesterase inhibition. Eighteen species belonging to Convolvulaceae, Crassulaceae, Euphorbiaceae, Leguminosae, Malvaceae, Moraceae, Nyctaginaceae and Rutaceae families were tested. The most active plants were Ipomoea asarifolia (IC50 = 0.12 mg/mL), Jatropha curcas (IC50 = 0.25 mg/mL), Jatropha gossypiifolia (IC50 = 0.05 mg/mL), Kalanchoe brasiliensis (IC50 = 0.16 mg/mL) and Senna alata (IC50 = 0.08 mg/mL). The most promising extracts were the Jatropha gossypiifolia and Senna alata species assuming there were compounds with a similar activity to galanthamine, which should contain about 1% of an active compound, or if present at lower levels even more active compounds than galanthamine (IC50 = 0.37 x 10-3 mg/mL) should be present.

Acetylcholinesterase inhibition by somes promising Brazilian medicinal plants

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CM. Feitosa

Full Text Available A microplate assay and a thin-layer chromatography (TLC "in situ" assay based on the Ellman assay was used to screen for acetylcholinesterase inhibitors from ethyl acetate and methanol extracts of Brazilian medicinal plants of families that, according to the literature, have traditional uses that might be connected with acetylcholinesterase inhibition. Eighteen species belonging to Convolvulaceae, Crassulaceae, Euphorbiaceae, Leguminosae, Malvaceae, Moraceae, Nyctaginaceae and Rutaceae families were tested. The most active plants were Ipomoea asarifolia (IC50 = 0.12 mg/mL, Jatropha curcas (IC50 = 0.25 mg/mL, Jatropha gossypiifolia (IC50 = 0.05 mg/mL, Kalanchoe brasiliensis (IC50 = 0.16 mg/mL and Senna alata (IC50 = 0.08 mg/mL. The most promising extracts were the Jatropha gossypiifolia and Senna alata species assuming there were compounds with a similar activity to galanthamine, which should contain about 1% of an active compound, or if present at lower levels even more active compounds than galanthamine (IC50 = 0.37 x 10-3 mg/mL should be present.

A conformational restriction approach to the development of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease.

Science.gov (United States)

Toda, Narihiro; Tago, Keiko; Marumoto, Shinji; Takami, Kazuko; Ori, Mayuko; Yamada, Naho; Koyama, Kazuo; Naruto, Shunji; Abe, Kazumi; Yamazaki, Reina; Hara, Takao; Aoyagi, Atsushi; Abe, Yasuyuki; Kaneko, Tsugio; Kogen, Hiroshi

2003-10-01

Alzheimer's disease (AD) has been treated with acetylcholinesterase (AChE) inhibitors such as donepezil. However, the clinical usefulness of AChE inhibitors is limited mainly due to their adverse peripheral effects. Depression seen in AD patients has been treated with serotonin transporter (SERT) inhibitors. We considered that combining SERT and AChE inhibition could improve the clinical usefulness of AChE inhibitors. In a previous paper, we found a potential dual inhibitor, 1, of AChE (IC50=101 nM) and SERT (IC50=42 nM), but its AChE inhibition activity was less than donepezil (IC50=10 nM). Here, we report the conformationally restricted (R)-18a considerably enhanced inhibitory activity against AChE (IC50=14 nM) and SERT (IC50=6 nM).

Analysis of Amaryllidaceae alkaloids from Zephyranthes grandiflora by GC/MS and their cholinesterase activity

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Lucie Cahlíková

2011-05-01

Full Text Available Amaryllidaceae are known as ornamental plants, furthermore some species of this family contain galanthamine, an acetylcholinesterase inhibitor approved for the treatment of Alzheimer's disease, and other alkaloids with interesting pharmacological activity. The chemical composition of alkaloids from Zephyranthes grandiflora Lindl. was analyzed by GC/MS. Seven known compounds, belonging to five structural types of Amaryllidaceae alkaloids, were identified. The alkaloid extract from the bulbs showed promising cholinesterase inhibitory activities against human blood acetylcholinesterase (HuAChE; IC50 39.2±3.0 µg/mL and human plasma butyrylcholinesterase (HuBuChE; IC50 356±9.3 µg/mL.

Analysis of Amaryllidaceae alkaloids from Zephyranthes grandiflora by GC/MS and their cholinesterase activity

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Lucie Cahlíková

2011-08-01

Full Text Available Amaryllidaceae are known as ornamental plants, furthermore some species of this family contain galanthamine, an acetylcholinesterase inhibitor approved for the treatment of Alzheimer's disease, and other alkaloids with interesting pharmacological activity. The chemical composition of alkaloids from Zephyranthes grandiflora Lindl. was analyzed by GC/MS. Seven known compounds, belonging to five structural types of Amaryllidaceae alkaloids, were identified. The alkaloid extract from the bulbs showed promising cholinesterase inhibitory activities against human blood acetylcholinesterase (HuAChE; IC50 39.2±3.0 µg/mL and human plasma butyrylcholinesterase (HuBuChE; IC50 356±9.3 µg/mL.

Testosterone 5alpha-reductase inhibitory active constituents of Piper nigrum leaf.

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Hirata, Noriko; Tokunaga, Masashi; Naruto, Shunsuke; Iinuma, Munekazu; Matsuda, Hideaki

2007-12-01

Previously we reported that Piper nigrum leaf extract showed a potent stimulation effect on melanogenesis and that (-)-cubebin (1) and (-)-3,4-dimethoxy-3,4-desmethylenedioxycubebin (2) were isolated as active constituents. As a part of our continuous studies on Piper species for the development of cosmetic hair-care agents, testosterone 5alpha-reductase inhibitory activity of aqueous ethanolic extracts obtained from several different parts of six Piper species, namely Piper nigrum, P. methysticum, P. betle, P. kadsura, P. longum, and P. cubeba, were examined. Among them, the extracts of P. nigrum leaf, P. nigrum fruit and P. cubeba fruit showed potent inhibitory activity. Activity-guided fractionation of P. nigrum leaf extract led to the isolation of 1 and 2. Fruits of P. cubeba contain 1 as a major lignan, thus inhibitory activity of the fruit may be attributable to 1. As a result of further assay on other known constituents of the cited Piper species, it was found that piperine, a major alkaloid amide of P. nigrum fruit, showed potent inhibitory activity, thus a part of the inhibitory activity of P. nigrum fruit may depend on piperine. The 5alpha-reductase inhibitory activities of 1 and piperine were found for the first time. In addition, the P. nigrum leaf extract showed in vivo anti-androgenic activity using the hair regrowth assay in testosterone sensitive male C57Black/6CrSlc strain mice.

Buprofezin inhibits acetylcholinesterase activity in B-biotype Bemisia tabaci.

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Cottage, Emma L A; Gunning, Robin V

2006-01-01

B-biotype Bemisia tabaci is a severe insect pest worldwide in many ornamental, agricultural, and horticultural industries. Control of this insect is hampered by resistance to many acetylcholinesterase (AChE)-inhibiting insecticides, such as organophosphates and carbamates. Consequently, insect growth regulators such as buprofezin, which act by inhibiting chitin synthesis, are being investigated for use against B-biotype B. tabaci in Australia. This study discusses the effects of buprofezin on B. tabaciAChE.

Identification of a trypsin-like site associated with acetylcholinesterase by affinity labelling with (/sup 3/H)diisopropyl fluorophosphate

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Small, D.H.; Chubb, I.W.

1988-07-01

In addition to its ability to hydrolyze acetylcholine, purified eel acetylcholinesterase possesses a trypsin-like endopeptidase activity. The tryptic activity is associated with a serine residue at a site that is distinct from the esteratic site. To label both the esteratic and tryptic sites, the enzyme was incubated with the serine hydrolase inhibitor (/sup 3/H)diisopropyl fluorophosphate. This compound labelled the protein in a biphasic manner, with both slow and rapid labelling kinetics. The time course of the rapid phase was similar to the time course of inactivation of the esteratic activity. The time course of the slow phase was similar to the time course of inactivation of the tryptic activity. Labelling of the nonesteratic site was inhibited by the trypsin inhibitor N alpha-p-tosyl-L-lysine chloromethyl ketone. The total number of sites labelled by (/sup 3/H)diisopropyl fluorophosphate on eel acetylcholinesterase was 2.6 mol/280,000 g protein, whereas the number of tryptic sites was less (0.52 mol/280,000 g). The results suggest that a subpopulation of acetylcholinesterase molecules may possess tryptic activity. Extensive chromatography of the purified enzyme by ion-exchange and gel filtration failed to separate the labelled tryptic component from acetylcholinesterase. On sodium dodecyl sulfate-polyacrylamide gels, the labelled tryptic component comigrated with a polypeptide of 50,000 molecular weight, which is a major proteolytic digestion product derived from the intact acetylcholinesterase monomer. Because of its localization in many noncholinergic peptide-containing cells, acetylcholinesterase could act as a neuropeptide processing enzyme in these cells.

Decorrelation of Neural-Network Activity by Inhibitory Feedback

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Einevoll, Gaute T.; Diesmann, Markus

2012-01-01

Correlations in spike-train ensembles can seriously impair the encoding of information by their spatio-temporal structure. An inevitable source of correlation in finite neural networks is common presynaptic input to pairs of neurons. Recent studies demonstrate that spike correlations in recurrent neural networks are considerably smaller than expected based on the amount of shared presynaptic input. Here, we explain this observation by means of a linear network model and simulations of networks of leaky integrate-and-fire neurons. We show that inhibitory feedback efficiently suppresses pairwise correlations and, hence, population-rate fluctuations, thereby assigning inhibitory neurons the new role of active decorrelation. We quantify this decorrelation by comparing the responses of the intact recurrent network (feedback system) and systems where the statistics of the feedback channel is perturbed (feedforward system). Manipulations of the feedback statistics can lead to a significant increase in the power and coherence of the population response. In particular, neglecting correlations within the ensemble of feedback channels or between the external stimulus and the feedback amplifies population-rate fluctuations by orders of magnitude. The fluctuation suppression in homogeneous inhibitory networks is explained by a negative feedback loop in the one-dimensional dynamics of the compound activity. Similarly, a change of coordinates exposes an effective negative feedback loop in the compound dynamics of stable excitatory-inhibitory networks. The suppression of input correlations in finite networks is explained by the population averaged correlations in the linear network model: In purely inhibitory networks, shared-input correlations are canceled by negative spike-train correlations. In excitatory-inhibitory networks, spike-train correlations are typically positive. Here, the suppression of input correlations is not a result of the mere existence of correlations between

NK cell activation: distinct stimulatory pathways counterbalancing inhibitory signals.

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Bakker, A B; Wu, J; Phillips, J H; Lanier, L L

2000-01-01

A delicate balance between positive and negative signals regulates NK cell effector function. Activation of NK cells may be initiated by the triggering of multiple adhesion or costimulatory molecules, and can be counterbalanced by inhibitory signals induced by receptors for MHC class I. A common pathway of inhibitory signaling is provided by immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in the cytoplasmic domains of these receptors which mediate the recruitment of SH2 domain-bearing tyrosine phosphate-1 (SHP-1). In contrast to the extensive progress that has been made regarding the negative regulation of NK cell function, our knowledge of the signals that activate NK cells is still poor. Recent studies of the activating receptor complexes have shed new light on the induction of NK cell effector function. Several NK receptors using novel adaptors with immunoreceptor tyrosine-based activation motifs (ITAMs) and with PI 3-kinase recruiting motifs have been implicated in NK cell stimulation.

Chagas disease: modulation of the inflammatory response by acetylcholinesterase in hematological cells and brain tissue.

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Silva, Aniélen D; Bottari, Nathieli B; do Carmo, Guilherme M; Baldissera, Matheus D; Souza, Carine F; Machado, Vanessa S; Morsch, Vera M; Schetinger, Maria Rosa C; Mendes, Ricardo E; Monteiro, Silvia G; Da Silva, Aleksandro S

2018-01-01

Chagas disease is an acute or chronic illness that causes severe inflammatory response, and consequently, it may activate the inflammatory cholinergic pathway, which is regulated by cholinesterases, including the acetylcholinesterase. This enzyme is responsible for the regulation of acetylcholine levels, an anti-inflammatory molecule linked to the inflammatory response during parasitic diseases. Thus, the aim of this study was to investigate whether Trypanosoma cruzi infection can alter the activity of acetylcholinesterase and acetylcholine levels in mice, and whether these alterations are linked to the inflammatory cholinergic signaling pathway. Twenty-four mice were divided into two groups: uninfected (control group, n = 12) and infected by T. cruzi, Y strain (n = 12). The animals developed acute disease with a peak of parasitemia on day 7 post-infection (PI). Blood, lymphocytes, and brain were analyzed on days 6 and 12 post-infection. In the brain, acetylcholine and nitric oxide levels, myeloperoxidase activity, and histopathology were analyzed. In total blood and brain, acetylcholinesterase activity decreased at both times. On the other hand, acetylcholinesterase activity in lymphocytes increased on day 6 PI compared with the control group. Infection by T. cruzi increased acetylcholine and nitric oxide levels and histopathological damage in the brain of mice associated to increased myeloperoxidase activity. Therefore, an intense inflammatory response in mice with acute Chagas disease in the central nervous system caused an anti-inflammatory response by the activation of the cholinergic inflammatory pathway.

Inhibitory effect of burdock leaves on elastase and tyrosinase activity

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Horng, Chi-Ting; Wu, Hsing-Chen; Chiang, Ni-Na; Lee, Chiu-Fang; Huang, Yu-Syuan; Wang, Hui-Yun; Yang, Jai-Sing; Chen, Fu-An

2017-01-01

Burdock (Arctium lappa L.) leaves generate a considerable amount of waste following burdock root harvest in Taiwan. To increase the use of burdock leaves, the present study investigated the optimal methods for producing burdock leaf extract (BLE) with high antioxidant polyphenolic content, including drying methods and solvent extraction concentration. In addition, the elastase and tyrosinase inhibitory activity of BLE was examined. Burdock leaves were dried by four methods: Shadow drying, oven drying, sun drying and freeze-drying. The extract solution was then subjected to total polyphenol content analysis and the method that produced BLE with the highest amount of total antioxidant components was taken forward for further analysis. The 1,1-diphenyl-2-pycrylhydrazyl scavenging, antielastase and antityrosinase activity of the BLE were measured to enable the evaluation of the antioxidant and skin aging-associated enzyme inhibitory activities of BLE. The results indicated that the total polyphenolic content following extraction with ethanol (EtOH) was highest using the freeze-drying method, followed by the oven drying, shadow drying and sun drying methods. BLE yielded a higher polyphenol content and stronger antioxidant activity as the ratio of the aqueous content of the extraction solvent used increased. BLE possesses marked tyrosinase and elastase inhibitory activities, with its antielastase activity notably stronger compared with its antityrosinase activity. These results indicate that the concentration of the extraction solvent was associated with the antioxidant and skin aging-associated enzyme inhibitory activity of BLE. The reactive oxygen species scavenging theory of skin aging may explain the tyrosinase and elastase inhibitory activity of BLE. In conclusion, the optimal method for obtaining BLE with a high antioxidant polyphenolic content was freeze-drying followed by 30–50% EtOH extraction. In addition, the antielastase and antityrosinase activities of the

Acetylcholinesterase inhibition and antioxidant activity of essential oils from Schinus areira L. and Schinus longifolia (Lindl.) Speg.

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Murray, Ana P; Gurovic, Maria S Vela; Rodriguez, Silvana A; Murray, María G; Ferrero, Adriana A

2009-06-01

The essential oils of Schinus areira L. and S. longifolia (Lindl.) Speg. (Anacardiaceae) have been studied for their in vitro anti-acetylcholinesterase and antioxidant activities. The chemical composition of the oils obtained by hydrodistillation was determined by GC-MS. Fruit and leaf oils of S. areira were analyzed separately. The essential oil from S. longifolia elicited marked enzymatic inhibition (IC50 = 20.0 +/- 1.0 microg/mL) and showed radical scavenger activity (IC50 = 25.2 +/- 2.4 microg/mL). The essential oil from S. areira leaves was more active than that of the fruits in both bioassays.

Histamine release inhibitory activity of Piper nigrum leaf.

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Hirata, Noriko; Naruto, Shunsuke; Inaba, Kazunori; Itoh, Kimihisa; Tokunaga, Masashi; Iinuma, Munekazu; Matsuda, Hideaki

2008-10-01

Oral administration of a methanolic extract of Piper nigrum leaf (PN-ext, 50, 200 and 500 mg/kg) showed a potent dose-dependent inhibition of dinitrofluorobenzene (DNFB)-induced cutaneous reaction at 1 h [immediate phase response (IPR)] after and 24 h [late phase response (LPR)] after DNFB challenge in mice which were passively sensitized with anti-dinitrophenyl (DNP) IgE antibody. Ear swelling inhibitory effect of PN-ext (50, 200 and 500 mg/kg, per os (p.o.)) on very late phase response (vLPR) in the model mice was significant but weaker than that on IPR. Oral administration of PN-ext (50, 200 and 500 mg/kg for 7 d) inhibited picryl chloride (PC)-induced ear swelling in PC sensitized mice. PN-ext exhibited in vitro inhibitory effect on compound 48/80-induced histamine release from rat peritoneal mast cells. Two lignans of PN-ext, (-)-cubebin (1) and (-)-3,4-dimethoxy-3,4-desmethylenedioxycubebin (2), were identified as major active principles having histamine release inhibitory activity.

Novel acetylcholinesterase inhibitors from Zijuan tea and biosynthetic pathway of caffeoylated catechin in tea plant.

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Wang, Wei; Fu, Xi-Wen; Dai, Xin-Long; Hua, Fang; Chu, Gang-Xiu; Chu, Ming-Jie; Hu, Feng-Lin; Ling, Tie-Jun; Gao, Li-Ping; Xie, Zhong-Wen; Wan, Xiao-Chun; Bao, Guan-Hu

2017-12-15

Zijuan tea is a special cultivar of Yunnan broad-leaf tea (Camellia sinensis var. assamica) with purple buds, leaves, and stems. Phytochemical study on this tea led to the discovery of three hydroxycinnamoylated catechins (HCCs) (1-3), seven other catechins (4-10), three proanthocyanidins (11-13), five flavones and flavone glycosides (14-18), two alkaloids (19, 20), one steroid (21), and one phenylpropanoid glycoside (22). The isolation and structural elucidation of the caffeoylated catechin (1) by means of spectroscopic techniques were described. We also provide the first evidence that 1 is synthesized via a two-step pathway in tea plant. The three HCCs (1-3) were investigated on their bioactivity through molecular modeling simulation and biochemical experiments. Our results show that they bind acetylcholinesterase (AChE) tightly and have strong AChE inhibitory activity with IC 50 value at 2.49, 11.41, 62.26μM, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antioxidant and Antiacetylcholinesterase Activities of Some Commercial Essential Oils and Their Major Compounds

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Smail Aazza

2011-09-01

Full Text Available The commercial essential oils of Citrus aurantium L., Cupressus sempervirens L., Eucalyptus globulus Labill., Foeniculum vulgare Mill. and Thymus vulgaris L., isolated by steam distillation by a company of Morocco were evaluated in terms of in vitro antioxidant activity through several methods. In vitro acetylcholinesterase inhibitory activity was also determined. Citrus limon (L. Burm. f. oil was also studied, but it was obtained by peel expression. The best antioxidant was T. vulgaris oil, independent of the method used, mainly due to the presence of the phenolic monoterpenes thymol and carvacrol, which when studied as single compounds also presented the best activities. Concerning the acetylcholinesterase inhibition activity, E. globulus was the most effective. Nevertheless its main components 1,8-cineole and limonene were not the most active, a feature that corresponded to d-3-carene.

Fruit Wines Inhibitory Activity Against α-Glucosidase.

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Cakar, Uros; Grozdanic, Nada; Petrovic, Aleksandar; Pejin, Boris; Nastasijevic, Branislav; Markovic, Bojan; Dordevic, Brizita

2017-01-01

Fruit wines are well known for their profound health-promoting properties including both enzyme activations and inhibitions. They may act preventive in regard to diabetes melitus and other chronic diseases. Potential α-glucosidase inhibitory activity of fruit wines made from blueberry, black chokeberry, blackberry, raspberry and sour cherry was the subject of this study. In order to increase the alcohol content due to enriched extraction of total phenolics, sugar was added in the fruit pomace of the half of the examined fruit wine samples. Compared with acarbose used as a positive control (IC50 = 73.78 µg/mL), all fruit wine samples exhibited higher α-glucosidase inhibitory activity. Indeed, blueberry wine samples stood out, both prepared with IC50 = 24.14 µg/mL, lyophilised extract yield 3.23% and without IC50 = 46.39 µg/mL, lyophilised extract yield 2.89% and with addition of sugar before fermentation. Chlorogenic acid predominantly contributed to α-glucosidase inhibitory activity of the blueberry, black chokeberry and sour cherry wine samples. However, ellagic acid, a potent α-glucosidase inhibitor possessing a planar structure, only slightly affected the activity of the blueberry wine samples, due to the lower concentration. In addition to this, molecular docking study of chlorogenic acid pointed out the importance of binding energy (-8.5 kcal/mol) for the inhibition of the enzyme. In summary, fruit wines made from blueberry should be primarily taken into consideration as a medicinal food targeting diabetes mellitus type 2 in the early stage, if additional studies would confirm their therapeutic potential for the control of postprandial hyperglycemia. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Analogous β-Carboline Alkaloids Harmaline and Harmine Ameliorate Scopolamine-Induced Cognition Dysfunction by Attenuating Acetylcholinesterase Activity, Oxidative Stress, and Inflammation in Mice

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Li, Shu-Ping; Wang, Yu-Wen; Qi, Sheng-Lan; Zhang, Yun-Peng; Deng, Gang; Ding, Wen-Zheng; Ma, Chao; Lin, Qi-Yan; Guan, Hui-Da; Liu, Wei; Cheng, Xue-Mei; Wang, Chang-Hong

2018-01-01

The analogous β-carboline alkaloids, harmaline (HAL) and harmine (HAR), possess a variety of biological properties, including acetylcholinesterase (AChE) inhibitory activity, antioxidant, anti-inflammatory, and many others, and have great potential for treating Alzheimer’s disease (AD). However, studies have showed that the two compounds have similar structures and in vitro AChE inhibitory activities but with significant difference in bioavailability. The objective of this study was to comparatively investigate the effects of HAL and HAR in memory deficits of scopolamine-induced mice. In the present study, mice were pretreated with HAL (2, 5, and 10 mg/kg), HAR (10, 20, and 30 mg/kg) and donepezil (5 mg/kg) by intragastrically for 7 days, and were daily intraperitoneal injected with scopolamine (1 mg/kg) to induce memory deficits and then subjected to behavioral evaluation by Morris water maze. To further elucidate the underlying mechanisms of HAL and HAR in improving learning and memory, the levels of various biochemical factors and protein expressions related to cholinergic function, oxidative stress, and inflammation were examined. The results showed that HAL and HAR could effectively ameliorate memory deficits in scopolamine-induced mice. Both of them exhibited an enhancement in cholinergic function by inhibiting AChE and inducing choline acetyltransferase (ChAT) activities, and antioxidant defense via increasing the antioxidant enzymes activities of superoxide dismutase and glutathione peroxidase, and reducing maleic diadehyde production, and anti-inflammatory effects through suppressing myeloperoxidase, tumor necrosis factor α, and nitric oxide as well as modulation of critical neurotransmitters such as acetylcholine (ACh), choline (Ch), L-tryptophan (L-Trp), 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (γ-GABA), and L-glutamic acid (L-Glu). Furthermore, the regulations of HAL on cholinergic function, inflammation, and neurotransmitters were more

Variation of Musca domestica L. acetylcholinesterase in Danish housefly populations

DEFF Research Database (Denmark)

Kristensen, Michael; Huang, Jing; Qiao, Chuan-Ling

2006-01-01

Anti-cholinesterase resistance is in many cases caused by modified acetylcholinesterase (MACE). A comparison was made of toxicological data and AChE activity gathered from 21 field populations and nine laboratory strains of houseflies, Musca domestica L., to elucidate the best way of generating...... data to provide advice for management strategies and gathering information for resistance risk assessment on the organophosphates azamethiphos and dimethoate and the carbamate methomyl, which have been the primary insecticides used against adult houseflies in Denmark. Cluster analysis was performed...... and > 2000 houseflies were assigned to one of three phenotypes based on total acetylcholinesterase activity as well as inhibition by azamethiphos, methomyl or omethoate. A cluster, i.e. a phenotype, with high total AChE activity and high sensitivity to azamethiphos and less sensitivity to inhibition...

An evaluation of the inhibition of human butyrylcholinesterase and acetylcholinesterase by the organophosphate chlorpyrifos oxon

International Nuclear Information System (INIS)

Shenouda, Josephine; Green, Paula; Sultatos, Lester

2009-01-01

Acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8) are enzymes that belong to the superfamily of α/β-hydrolase fold proteins. While they share many characteristics, they also possess many important differences. For example, whereas they have about 54% amino acid sequence identity, the active site gorge of acetylcholinesterase is considerably smaller than that of butyrylcholinesterase. Moreover, both have been shown to display simple and complex kinetic mechanisms, depending on the particular substrate examined, the substrate concentration, and incubation conditions. In the current study, incubation of butyrylthiocholine in a concentration range of 0.005-3.0 mM, with 317 pM human butyrylcholinesterase in vitro, resulted in rates of production of thiocholine that were accurately described by simple Michaelis-Menten kinetics, with a K m of 0.10 mM. Similarly, the inhibition of butyrylcholinesterase in vitro by the organophosphate chlorpyrifos oxon was described by simple Michaelis-Menten kinetics, with a k i of 3048 nM -1 h -1 , and a K D of 2.02 nM. In contrast to inhibition of butyrylcholinesterase, inhibition of human acetylcholinesterase by chlorpyrifos oxon in vitro followed concentration-dependent inhibition kinetics, with the k i increasing as the inhibitor concentration decreased. Chlorpyrifos oxon concentrations of 10 and 0.3 nM gave k i s of 1.2 and 19.3 nM -1 h -1 , respectively. Although the mechanism of concentration-dependent inhibition kinetics is not known, the much smaller, more restrictive active site gorge of acetylcholinesterase almost certainly plays a role. Similarly, the much larger active site gorge of butyrylcholinesterase likely contributes to its much greater reactivity towards chlorpyrifos oxon, compared to acetylcholinesterase.

Plants from Brazilian Cerrado with potent tyrosinase inhibitory activity.

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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.

Chemical Composition, Antioxidant and Anticholinesterase Activities of the Essential Oil of Salvia chrysophylla Staph

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Mehmet Emin Duru

2012-01-01

Full Text Available The essential oil from the aerial parts of Salvia chrysophylla Staph (Lamiaceae, endemic to Turkey, was investigated by using GC and GC-MS. Fifty-four of 55 components, represented 99.52% of the total oil were identified. The major components of the essential oil were found to be α-terpinenyl acetate (36.31%, β-caryophyllene (15.29%, linalool (8.12% and β-elemene (4.26%. The antioxidant activity of the oil was investigated by using 2,2-diphenyl-1-picrylhydrazyl (DPPH and β-carotene/linoleic acid tests. Anticholinesterase activity was screened against acetylcholinesterase and butyrylcholinesterase which are the chief enzymes of Alzheimer’s diseases. The essential oil showed weak antioxidant activity. However, at 1 mg/mL concentration, the essential oil exhibited mild acetylcholinesterase (52.5±2.0% and modarate butyrylcholinesterase (76.5±2.7% inhibitory activity.

Coconut (Cocos nucifera) Ethanolic Leaf Extract Reduces Amyloid-β (1-42) Aggregation and Paralysis Prevalence in Transgenic Caenorhabditis elegans Independently of Free Radical Scavenging and Acetylcholinesterase Inhibition.

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Manalo, Rafael Vincent; Silvestre, Maries Ann; Barbosa, Aza Lea Anne; Medina, Paul Mark

2017-04-21

Virgin coconut oil (VCO) has been the subject of several studies which have aimed to alleviate Alzheimer's disease (AD) pathology, focusing on in vitro antioxidant and acetylcholinesterase (AChE) inhibitory activities. Here, we studied an underutilized and lesser-valued part of the coconut tree, specifically the leaves, using in vitro and in vivo approaches. Coconut leaf extract (CLE) was screened for antioxidant and AChE inhibitory properties in vitro and therapeutic effects in two strains of transgenic Caenorhabditis elegans expressing amyloid-β 1-42 (Aβ 1-42 ) in muscle cells. CLE demonstrated free radical scavenging activity with an EC 50 that is 79-fold less compared to ascorbic acid, and an AChE inhibitory activity that is 131-fold less compared to Rivastigmine. Surprisingly, in spite of its low antioxidant activity and AChE inhibition, CLE reduced Aβ deposits by 30.31% in CL2006 in a dose-independent manner, and reduced the percentage of paralyzed nematodes at the lowest concentration of CLE (159.38 μg/mL), compared to dH₂O/vehicle (control). Phytochemical analysis detected glycosides, anthocyanins, and hydrolyzable tannins in CLE, some of which are known to be anti-amyloidogenic. Taken together, these findings suggest that CLE metabolites alternatively decrease AB 1-42 aggregation and paralysis prevalence independently of free radical scavenging and AChE inhibition, and this warrants further investigation on the bioactive compounds of CLE.

Comparison of antioxidant, anticholinesterase, and antidiabetic activities of three curcuminoids isolated from Curcuma longa L.

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Kalaycıoğlu, Zeynep; Gazioğlu, Işıl; Erim, F Bedia

2017-12-01

Antioxidant, anticholinesterase and antidiabetic activities of three curcuminoids isolated from the Curcuma longa were simultaneously tested and compared in this study. The highest antioxidant power was detected for curcumin with the applied methods. The drug potentials of curcuminoids for Alzheimer's disease were controlled. Bisdemethoxycurcumin (BDMC) showed substantial inhibitory activity. The activity of demethoxycurcumin (DMC) followed BDMC, whereas curcumin showed very little acetylcholinesterase inhibition activity. Antidiabetic activity of curcuminoids was evaluated by their α-glucosidase inhibitory activities. All curcuminoids show activities with decreasing order as BDMC > curcumin > DMC. The significant activities of BDMC compared to its isomers and examination of chemical structures of isomers might be a starting point in designing new drugs for Alzheimer's and Diabetes Mellitus.

Shift in aggregation, ROS generation, antioxidative defense, lysozyme and acetylcholinesterase activities in the cells of an Indian freshwater sponge exposed to washing soda (sodium carbonate).

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Mukherjee, Soumalya; Ray, Mitali; Ray, Sajal

2016-09-01

Washing soda, chemically identified as anhydrous sodium carbonate, is a popular cleaning agent among the rural and urban populations of India which often contaminates the freshwater ponds and lakes, the natural habitat of sponge Eunapius carteri. Present investigation deals with estimation of cellular aggregation, generation of ROS and activities of antioxidant enzymes, lysozyme and acetylcholinesterase in the cells of E. carteri under the environmentally realistic concentrations of washing soda. Prolonged treatment of washing soda inhibited the degree of cellular aggregation. Experimental exposure of 8 and 16mg/l of sodium carbonate for 48h elevated the physiological level of reactive oxygen species (ROS) generation in the agranulocytes, semigranulocytes and granulocytes of E. carteri, whereas, treatment of 192h inhibited the ROS generation in three cellular morphotypes. Activities of superoxide dismutase, catalase and glutathione-S-transferase were recorded to be inhibited under prolonged exposure of washing soda. Washing soda mediated inhibition of ROS generation and depletion in the activities of antioxidant enzymes were indicative to an undesirable shift in cytotoxic status and antioxidative defense in E. carteri. Inhibition in the activity of lysozyme under the treatment of sodium carbonate was suggestive to a severe impairment of the innate immunological efficiency of E. carteri distributed in the washing soda contaminated habitat. Washing soda mediated inhibition in the activity of acetylcholinesterase indicated its neurotoxicity in E. carteri. Washing soda, a reported environmental contaminant, affected adversely the immunophysiological status of E. carteri with reference to cellular aggregation, oxidative stress, antioxidative defense, lysozyme and acetylcholinesterase activity. Copyright © 2016 Elsevier Inc. All rights reserved.

Geissoschizine methyl ether N-oxide, a new alkaloid with antiacetylcholinesterase activity from Uncaria rhynchophylla.

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Jiang, Wei-Wei; Su, Jia; Wu, Xing-De; He, Juan; Peng, Li-Yan; Cheng, Xiao; Zhao, Qin-Shi

2015-01-01

Geissoschizine methyl ether N-oxide, a new oxindole alkaloid, along with 14 known alkaloids, was isolated from the aerial part of Uncaria rhynchophylla. Their structures were identified by comprehensive spectral methods, including 2D NMR experiments, and confirmed by comparing with the literature data. In vitro acetylcholinesterase (AChE) inhibitory activity assay showed that the new compound exhibited anti-AChE activity with IC₅₀ value of 23.4 μM.

Internal Diffusion-Controlled Enzyme Reaction: The Acetylcholinesterase Kinetics.

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Lee, Sangyun; Kim, Ji-Hyun; Lee, Sangyoub

2012-02-14

Acetylcholinesterase is an enzyme with a very high turnover rate; it quenches the neurotransmitter, acetylcholine, at the synapse. We have investigated the kinetics of the enzyme reaction by calculating the diffusion rate of the substrate molecule along an active site channel inside the enzyme from atomic-level molecular dynamics simulations. In contrast to the previous works, we have found that the internal substrate diffusion is the determinant of the acetylcholinesterase kinetics in the low substrate concentration limit. Our estimate of the overall bimolecular reaction rate constant for the enzyme is in good agreement with the experimental data. In addition, the present calculation provides a reasonable explanation for the effects of the ionic strength of solution and the mutation of surface residues of the enzyme. The study suggests that internal diffusion of the substrate could be a key factor in understanding the kinetics of enzymes of similar characteristics.

HPLC based activity profiling for 5-lipoxygenase inhibitory activity in Isatis tinctoria leaf extracts.

Science.gov (United States)

Oberthür, C; Jäggi, R; Hamburger, M

2005-06-01

In the pursuit of the anti-inflammatory constituents in lipophilic woad extracts, the 5-lipoxygenase (5-LOX) inhibitory activity was investigated by HPLC-based activity profiling. In a low-resolution profiling, two time windows with peaks of activity were found. The first coincided with tryptanthrin, a known dual inhibitor of cyclooxygenase-2 (COX-2) and 5-LOX, whereas the major inhibitory fraction was towards the end of the HPLC run. The active fractions were profiled in a peak-resolved manner, and the compounds analyzed by LC-MS, GC and TLC. The activity in the lipophilic fractions of the Isatis extract could be linked to an unsaturated fatty acid, alpha-linolenic acid.

Improving the knowledge on Piper betle: targeted metabolite analysis and effect on acetylcholinesterase.

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Valentão, Patrícia; Gonçalves, Rui F; Belo, Cristóvão; de Pinho, Paula Guedes; Andrade, Paula B; Ferreres, Federico

2010-10-01

Piper betle is a species growing in South East Asia, where its leaves are economically and medicinally important. To screen the highest possible number of volatile and semivolatile components, the leaves were subjected to headspace solid-phase microextraction, hydrodistillation and Soxhlet extraction, prior to analysis by GC/MS. Fifty compounds (identified by comparison with standard compounds or tentatively by National Institute of Standards and Technology database) were determined, 23 being described for the first time in this matrix. An aqueous extract was also analysed, in which only seven compounds were characterized. The organic acids' composition of this extract was determined by HPLC/UV and eight compounds are reported for the first time in P. betle. This extract also displayed acetylcholinesterase inhibitory capacity.

New polyacetylenes glycoside from Eclipta prostrate with DGAT inhibitory activity.

Science.gov (United States)

Meng, Xiao; Li, Ban-Ban; Lin, Xin; Jiang, Yi-Yu; Zhang, Le; Li, Hao-Ze; Cui, Long

2018-06-08

One new polyacetylene glycoside eprostrata Ⅰ (1), together with seven known compounds (2-8), were isolated from Eclipta prostrata. Their structures were elucidated on the basis of spectroscopic and physico-chemical analyses. All the isolates were evaluated inhibitory activity on DGAT in an in vitro assay. Compounds 1-8 were found to exhibit inhibitory activity of DGAT1 with IC 50 values ranging from 74.4 ± 1.3 to 101.1 ± 1.1 μM.

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

International Nuclear Information System (INIS)

Schallreuter, Karin U.; University of Bradford; Elwary, Souna M.; Parkin, Susan M.; Wood, John M.

2007-01-01

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 -3 M) via a specific EF-hand calcium binding site, whereas acetylcholinesterase (AchE) is not affected. 45 Calcium labelling and computer simulation confirmed the presence of one EF-hand binding site per subunit which is disrupted by H 2 O 2 -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 m 2 surface area with its calcium gradient in the 10 -3 M range, our results implicate calcium-activated BuchE as a major protective mechanism against suicide inhibition of AchE by organophosphates in this non-neuronal tissue

Hydrogen peroxide modifies both activity and isoforms of acetylcholinesterase in human neuroblastoma SH-SY5Y cells

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Alba Garcimartín

2017-08-01

Full Text Available The involvement of cholinergic system and the reactive oxygen species (ROS in the pathogenesis of some degenerative diseases has been widely reported; however, the specific impact of hydrogen peroxide (H2O2 on the acetylcholinesterase (AChE activity as well as AChE isoform levels has not been clearly established. Hence, the purpose of present study is to clarify whether H2O2 alters these parameters.Human neuroblastoma SH-SY5Y cells were treated with H2O2 (1–1000 µM for 24 h and AChE activity and AChE and cytochrome c levels were evaluated. AChE activity was strongly increased from 1 µM to 1000 µM of H2O2. The results of the kinetic study showed that H2O2 affected Vmax but not Km; and also that H2O2 changed the sigmoid kinetic observed in control samples to hyperbolic kinetic. Thus, results suggest that H2O2 acts as an allosteric activators. In addition, H2O2, (100–1000 µM reduced the total AChE content and modified its isoform profile (mainly 50-, 70-, and 132-kDa·H2O2 from 100 µM to 1000 µM induced cytochrome c release confirming cell death by apoptosis. All these results together suggest: a the involvement of oxidative stress in the imbalance of AChE; and b treatment with antioxidant agents may be a suitable strategy to protect cholinergic system alterations promoted by oxidative stress. Keywords: Acetylcholinesterase, Hydrogen peroxide, Alternative splicing, Cell culture, Cell death

Discovery of potent and selective acetylcholinesterase (AChE) inhibitors: acacetin 7-O-methyl ether Mannich base derivatives synthesised from easy access natural product naringin.

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Liu, Hao-Ran; Men, Xue; Gao, Xiao-Hui; Liu, Lin-Bo; Fan, Hao-Qun; Xia, Xin-Hua; Wang, Qiu-An

2018-03-01

Naringin, as a component universal existing in the peel of some fruits or medicinal plants, was usually selected as the material to synthesise bioactive derivates since it was easy to gain with low cost. In present investigation, eight new acacetin-7-O-methyl ether Mannich base derivatives (1-8) were synthesised from naringin. The bioactivity evaluation revealed that most of them exhibited moderate or potent acetylcholinesterase (AChE) inhibitory activity. Among them, compound 7 (IC 50 for AChE = 0.82 ± 0.08 μmol•L -1 , IC 50 for BuChE = 46.30 ± 3.26 μmol•L -1 ) showed a potent activity and high selectivity compared with the positive control Rivastigmine (IC 50 for AChE = 10.54 ± 0.86 μmol•L -1 , IC 50 for BuChE = 0.26 ± 0.08 μmol•L -1 ). The kinetic study suggested that compound 7 bind to AChE with mix-type inhibitory profile. Molecular docking study revealed that compound 7 could combine both catalytic active site (CAS) and peripheral active site (PAS) of AChE with four points (Trp84, Trp279, Tyr70 and Phe330), while it could bind with BuChE via only His 20.

Guarana (Paullinia cupana) ameliorates memory impairment and modulates acetylcholinesterase activity in Poloxamer-407-induced hyperlipidemia in rat brain.

Science.gov (United States)

Ruchel, Jader B; Braun, Josiane B S; Adefegha, Stephen A; Guedes Manzoni, Alessandra; Abdalla, Fátima H; de Oliveira, Juliana S; Trelles, Kelly; Signor, Cristiane; Lopes, Sônia T A; da Silva, Cássia B; Castilhos, Lívia G; Rubin, Maribel A; Leal, Daniela B R

2017-01-01

Hyperlipidemia is a risk factor for the development of cognitive dysfunction and atherosclerosis. Natural compounds have recently received special attention in relation to the treatment of disease due to their low cost and wide margin of safety. Thus, the aim of this study was to determine the possible preventive effect of guarana powder (Paullinia cupana) on memory impairment and acetylcholinesterase (AChE) activity in the brain structures of rats with Poloxamer-407-induced hyperlipidemia. Adult male Wistar rats were pretreated with guarana (12.5, 25 and 50mg/kg/day) and caffeine (0.2mg/kg/day) by gavage for a period of 30days. Simvastatin (0.04mg/kg) was administered as a comparative standard. Acute hyperlipidemia was induced with intraperitoneal injections of 500mg/kg of Poloxamer-407. Memory tests and evaluations of anxiety were performed. The cortex, cerebellum, hippocampus, hypothalamus and striatum were separated to assess acetylcholinesterase activity. Our results revealed that guarana powder was able to reduce the levels of TC and LDL-C in a manner similar to simvastatin. Guarana powder also partially reduced the liver damage caused by hyperlipidemia. Guarana was able to prevent changes in the activity of AChE and improve memory impairment due to hyperlipidemia. Guarana powder may therefore be a source of promising phytochemicals that can be used as adjuvant therapy in the management of hyperlipidemia and cognitive disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

Antibacterial and glucosyltransferase enzyme inhibitory activity of helmyntostachyszelanica

Science.gov (United States)

Kuspradini, H.; Putri, AS; Mitsunaga, T.

2018-04-01

Helminthostachyszeylanica is a terrestrial, herbaceous, fern-like plant of southeastern Asia and Australia, commonly known as tunjuk-langit. This kind of plant have a medicinal properties such as treatment of malaria, dysentery and can be eaten with betel in the treatment of whooping cough. To evaluate the scientific basis for the use of the plant, the antimicrobial activities of extracts of the stem and leaves were evaluated. The bacteria used in this study is Streptococcus sobrinus, a species of gram-positive, that may be associated with human dental caries. The dried powdered plant parts were extracted using methanol and 50% aqueous extract and screened for their antibacterial effects of Streptococcus sobrinus using the 96 well-plate microdilution broth method. The inhibitory activities of its related enzyme were also determined. The plant extracts showed variable antibacterial and Glucosyltransferase enzyme inhibitory activity while some extracts could not cause any inhibition. It was shown that 50% ethanolics of Helminthostachyzeylanica stem have a potency as anti dental caries agents.

Dual Binding Site and Selective Acetylcholinesterase Inhibitors Derived from Integrated Pharmacophore Models and Sequential Virtual Screening

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Shikhar Gupta

2014-01-01

Full Text Available In this study, we have employed in silico methodology combining double pharmacophore based screening, molecular docking, and ADME/T filtering to identify dual binding site acetylcholinesterase inhibitors that can preferentially inhibit acetylcholinesterase and simultaneously inhibit the butyrylcholinesterase also but in the lesser extent than acetylcholinesterase. 3D-pharmacophore models of AChE and BuChE enzyme inhibitors have been developed from xanthostigmine derivatives through HypoGen and validated using test set, Fischer’s randomization technique. The best acetylcholinesterase and butyrylcholinesterase inhibitors pharmacophore hypotheses Hypo1_A and Hypo1_B, with high correlation coefficient of 0.96 and 0.94, respectively, were used as 3D query for screening the Zinc database. The screened hits were then subjected to the ADME/T and molecular docking study to prioritise the compounds. Finally, 18 compounds were identified as potential leads against AChE enzyme, showing good predicted activities and promising ADME/T properties.

Screening of acetylcholinesterase inhibitors in snake venom by electrospray mass spectrometry

NARCIS (Netherlands)

Liesener, A.; Perchuc, Anna-Maria; Schöni, Reto; Schebb, Nils Helge; Wilmer, Marianne; Karst, U.

2007-01-01

An electrospray ionization/mass spectrometry (ESI/MS)-based assay for the determination of acetylcholinesterase (AChE)-inhibiting activity in snake venom was developed. It allows the direct monitoring of the natural AChE substrate acetylcholine (AC) and the respective product choline. The assay

Characterization of angiotensin-converting enzyme inhibitory activity of fermented milk produced by Lactobacillus helveticus.

Science.gov (United States)

Chen, Yongfu; Li, Changkun; Xue, Jiangang; Kwok, Lai-yu; Yang, Jie; Zhang, Heping; Menghe, Bilige

2015-08-01

Hypertension affects up to 30% of the adult population in most countries. It is a known risk factor for cardiovascular diseases, including coronary heart disease, peripheral artery disease, and stroke. Owing to the increased health awareness of consumers, the application of angiotensin-converting enzyme (ACE)-inhibitory peptides produced by Lactobacillushelveticus to prevent or control high blood pressure has drawn wide attention. A total of 59 L. helveticus strains were isolated from traditional fermented dairy products and the ACE-inhibitory activity of the fermented milks produced with the isolated microorganisms was assayed. The ACE-inhibitory activity of 38 L. helveticus strains was more than 50%, and 3 strains (IMAU80872, IMAU80852, and IMAU80851) expressing the highest ACE-inhibitory activity were selected for further studies. Particularly, the gastrointestinal protease tolerance and thermostability of the ACE-inhibitory activity in the fermented milks were assessed. Based on these 2 criteria, IMAU80872 was found to be superior over the other 2 strains. Furthermore, IMAU80872 exhibited a high in vitro ACE-inhibitory activity at the following fermentation conditions: fermentation temperature at 40°C, inoculation concentration of 1×10(6) cfu/mL, and fermentation for 18h. Finally, by using ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry analysis, we observed changes of the metabolome along the milk fermentation process of IMAU80872. Furthermore, 6 peptides were identified, which might have ACE-inhibitory activity. In conclusion, we identified a novel ACE-inhibitory L. helveticus strain suitable for the production of fermented milk or other functional dairy products. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

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

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M. Julia Arcos-Martínez

2010-03-01

Full Text Available 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 concentration and potential applied, were established. Under these conditions, repeatability and reproducibility of biosensors were determined, reaching values below 4% in terms of relative standard deviation. The detection limit obtained for arsenic was 1.1 × 10−8 M for Ach/SPCE biosensor. Analysis of the possible effect of the presence of foreign ions in the solution was performed. The method was applied to determine levels of arsenic in spiked tap water samples.

Bovine nucleus caudatus acetylcholinesterase: active site determination and investigation of a dimeric form obtained by selective proteolysis

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Landauer, P.; Ruess, K.P.; Lieflaender, M.

1984-09-01

The number of catalytic subunits of purified bovine nucleus caudatus acetylcholinesterase (E.C. 3.1.1.7) has been determined by active site labelling with (3H)diisopropyl fluorophosphate ((3H)DFP). The 10.5 S, 16 S, and 20 S forms were estimated to contain two, four, and six active sites, respectively, per molecule. A 4.8 S form, which showed a weak amphiphile-dependent activity behavior, was obtained by selective proteolytic digestion with pronase. The inability of the purified 4.8 S form to aggregate after detergent removal, and the molecular mass in the range of 130-165 kD under nondenaturating conditions, indicate that this form is a dimeric form, lacking those hydrophobic regions responsible for aggregation.

Inactivation of acetylcholinesterase by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride.

Science.gov (United States)

Zang, Lun-Yi; Misra, Hara P

2003-12-01

The neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) has been shown to reversibly inhibit the activity of acetylcholinesterase. The inactivation of the enzyme was detected by monitoring the accumulation of yellow color produced from the reaction between thiocholine and dithiobisnitrobenzoate ion. The kinetic parameter, Km for the substrate (acetylthiocholine), was found to be 0.216 mM and Ki for MPTP inactivation of acetylcholinesterase was found to be 2.14 mM. The inactivation of enzyme by MPTP was found to be dose-dependent. It was found that MPTP is neither a substrate of AChE nor the time-dependent inactivator. The studies of reaction kinetics indicate the inactivation of AChE to be a linear mixed-type inhibition. The dilution assays indicate that MPTP is a reversible inhibitor for AChE. These data suggest that once MPTP enters the basal ganglia of the brain, it can inactivate the acetylcholinesterase enzyme and thereby increase the acetylcholine level in the basal ganglia of brain, leading to potential cell dysfunction. It appears that the nigrostriatal toxicity by MPTP leading to Parkinson's disease-like syndrome may, in part, be mediated via the acetylcholinesterase inactivation.

Structural Requirements of Alkylglyceryl-l-Ascorbic Acid Derivatives for Melanogenesis Inhibitory Activity.

Science.gov (United States)

Taira, Norihisa; Katsuyama, Yushi; Yoshioka, Masato; Muraoka, Osamu; Morikawa, Toshio

2018-04-10

l-Ascorbic acid has multifunctional benefits on skin aesthetics, including inhibition of melanin production, and is widely used in cosmetics. It, however, has low stability and poor skin penetration. We hypothesize that alkylglyceryl-l-ascorbic acid derivatives, highly stable vitamin C-alkylglycerol conjugates, would have similar anti-melanogenic activity with better stability and penetration. We test 28 alkylglyceryl-l-ascorbic acid derivatives ( 1 - 28 ) on theophylline-stimulated B16 melanoma 4A5 cells to determine if they inhibit melanogenesis and establish any structure-function relationships. Although not the most potent inhibitors, 3- O -(2,3-dihydroxypropyl)-2- O -hexyl-l-ascorbic acid ( 6 , IC 50 = 81.4 µM) and 2- O -(2,3-dihydroxypropyl)-3- O -hexyl-l-ascorbic acid ( 20 , IC 50 = 117 µM) are deemed the best candidate derivatives based on their inhibitory activities and low toxicities. These derivatives are also found to be more stable than l-ascorbic acid and to have favorable characteristics for skin penetration. The following structural requirements for inhibitory activity of alkylglyceryl-l-ascorbic acid derivatives are also determined: (i) alkylation of glyceryl-l-ascorbic acid is essential for inhibitory activity; (ii) the 3- O -alkyl-derivatives ( 2 - 14 ) exhibit stronger inhibitory activity than the corresponding 2- O -alkyl-derivatives ( 16 - 28 ); and (iii) derivatives with longer alkyl chains have stronger inhibitory activities. Mechanistically, our studies suggest that l-ascorbic acid derivatives exert their effects by suppressing the mRNA expression of tyrosinase and tyrosine-related protein-1.

Synthesis, docking and acetylcholinesterase inhibitory assessment of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives with potential anti-Alzheimer effects

Science.gov (United States)

2013-01-01

Background Alzheimer’s disease (AD) as neurodegenerative disorder, is the most common form of dementia accounting for about 50-60% of the overall cases of dementia among persons over 65 years of age. Low acetylcholine (ACh) concentration in hippocampus and cortex areas of the brain is one of the main reasons for this disease. In recent years, acetylcholinesterase (AChE) inhibitors like donepezil with prevention of acetylcholine hydrolysis can enhance the duration of action of acetylcholine in synaptic cleft and improve the dementia associated with Alzheimer’s disease. Results Design, synthesis and assessment of anticholinesterase activity of 2-(2-(4-Benzylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives showed prepared compounds can function as potential acetylcholinesterase inhibitor. Among 12 synthesized derivatives, compound 4a with ortho chlorine moiety as electron withdrawing group exhibited the highest potency in these series (IC50 = 0.91 ± 0.045 μM) compared to donepezil (IC50 = 0.14 ± 0.03 μM). The results of the enzyme inhibition test (Ellman test) showed that electron withdrawing groups like Cl, F and NO2 can render the best effect at position ortho and para of the phenyl ring. But compound 4g with methoxy group at position 3(meta) afforded a favorable potency (IC50 = 5.5 ± 0.7 μM). Furthermore, docking study confirmed a same binding mode like donepezil for compound 4a. Conclusions Synthesized compounds 4a-4l could be proposed as potential anticholinesterase agents. PMID:23758724

Synthesis, Docking and Acetylcholinesterase Inhibitory Assessment of 2-(2-(4-Benzylpiperazin-1-YlEthylIsoindoline-1,3-Dione Derivatives with Potential Anti-Alzheimer Effects

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Ahmad Mohammadi-Farani

2013-06-01

Full Text Available Background:Alzheimer’s disease (AD as neurodegenerative disorder, is the most common form of dementia accounting for about 50-60% of the overall cases of dementia among persons over 65 years of age. Low acetylcholine (ACh concentration in hippocampus and cortex areas of the brain is one of the main reasons for this disease. In recent years, acetylcholinesterase (AChE inhibitors like donepezil with prevention of acetylcholine hydrolysis can enhance the duration of action of acetylcholine in synaptic cleft and improve the dementia associated with Alzheimer’s disease.Results:Design, synthesis and assessment of anticholinesterase activity of 2-(2-(4-Benzylpiperazin-1-ylethylisoindoline-1,3-dione derivatives showed prepared compounds can function as potential acetylcholinesterase inhibitor. Among 12 synthesized derivatives, compound 4a with ortho chlorine moiety as electron withdrawing group exhibited the highest potency in these series (IC50 = 0.91 ± 0.045 μM compared to donepezil (IC50 = 0.14 ± 0.03 μM. The results of the enzyme inhibition test (Ellman test showed that electron withdrawing groups like Cl, F and NO2 can render the best effect at position ortho and para of the phenyl ring. But compound 4g with methoxy group at position 3(meta afforded a favorable potency (IC50 = 5.5 ± 0.7 μM. Furthermore, docking study confirmed a same binding mode like donepezil for compound 4a.Conclusions:Synthesized compounds 4a-4l could be proposed as potential anticholinesterase agents.

Influence of acetylcholinesterase immobilization on the photoluminescence properties of mesoporous silicon surface

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Saleem, Muhammad [Department of Chemistry, Kongju National University, Gongju, Chungnam 314-701 (Korea, Republic of); Rafiq, Muhammad; Seo, Sung-Yum [Department of Biology, Kongju National University, Gongju, Chungnam 314-701 (Korea, Republic of); Lee, Ki Hwan, E-mail: khlee@kongju.ac.kr [Department of Chemistry, Kongju National University, Gongju, Chungnam 314-701 (Korea, Republic of)

2014-07-01

Acetylcholinesterase immobilized p-type porous silicon surface was prepared by covalent attachment. The immobilization procedure was based on support surface chemical oxidation, silanization, surface activation with cyanuric chloride and finally covalent attachment of free enzyme on the cyanuric chloride activated porous silicon surface. Different pore diameter of porous silicon samples were prepared by electrochemical etching in HF based electrolyte solution and appropriate sample was selected suitable for enzyme immobilization with maximum trapping ability. The surface modification was studied through field emission scanning electron microscope, EDS, FT-IR analysis, and photoluminescence measurement by utilizing the fluctuation in the photoluminescence of virgin and enzyme immobilized porous silicon surface. Porous silicon showed strong photoluminescence with maximum emission at 643 nm and immobilization of acetylcholinesterase on porous silicon surface cause considerable increment on the photoluminescence of porous silicon material while acetylcholinesterase free counterpart did not exhibit any fluorescence in the range of 635–670 nm. The activities of the free and immobilized enzymes were evaluated by spectrophotometric method by using neostigmine methylsulfate as standard enzyme inhibitor. The immobilized enzyme exhibited considerable response toward neostigmine methylsulfate in a dose dependent manner comparable with that of its free counterpart alongside enhanced stability, easy separation from the reaction media and significant saving of enzyme. It was believed that immobilized enzyme can be exploited in organic and biomolecule synthesis possessing technical and economical prestige over free enzyme and prominence of easy separation from the reaction mixture.

Influence of acetylcholinesterase immobilization on the photoluminescence properties of mesoporous silicon surface

International Nuclear Information System (INIS)

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

2014-01-01

Acetylcholinesterase immobilized p-type porous silicon surface was prepared by covalent attachment. The immobilization procedure was based on support surface chemical oxidation, silanization, surface activation with cyanuric chloride and finally covalent attachment of free enzyme on the cyanuric chloride activated porous silicon surface. Different pore diameter of porous silicon samples were prepared by electrochemical etching in HF based electrolyte solution and appropriate sample was selected suitable for enzyme immobilization with maximum trapping ability. The surface modification was studied through field emission scanning electron microscope, EDS, FT-IR analysis, and photoluminescence measurement by utilizing the fluctuation in the photoluminescence of virgin and enzyme immobilized porous silicon surface. Porous silicon showed strong photoluminescence with maximum emission at 643 nm and immobilization of acetylcholinesterase on porous silicon surface cause considerable increment on the photoluminescence of porous silicon material while acetylcholinesterase free counterpart did not exhibit any fluorescence in the range of 635–670 nm. The activities of the free and immobilized enzymes were evaluated by spectrophotometric method by using neostigmine methylsulfate as standard enzyme inhibitor. The immobilized enzyme exhibited considerable response toward neostigmine methylsulfate in a dose dependent manner comparable with that of its free counterpart alongside enhanced stability, easy separation from the reaction media and significant saving of enzyme. It was believed that immobilized enzyme can be exploited in organic and biomolecule synthesis possessing technical and economical prestige over free enzyme and prominence of easy separation from the reaction mixture.

Aldose Reductase Inhibitory and Antiglycation Activities of Four ...

African Journals Online (AJOL)

Aldose Reductase Inhibitory and Antiglycation Activities of Four Medicinal Plant Standardized Extracts and Their Main Constituents for the Prevention of ... levels in galactosemic condition by using reverse phase high pressure liquid chromatography (RP-HPLC) and gas liquid chromatography (GLC) was determined.

Comparative study of acetylcholinesterase and glutathione S-transferase activities of closely related cave and surface Asellus aquaticus (Isopoda: Crustacea.

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Anita Jemec

Full Text Available The freshwater isopod crustacean Asellus aquaticus has recently been developed as an emerging invertebrate cave model for studying evolutionary and developmental biology. Mostly morphological and genetic differences between cave and surface A. aquaticus populations have been described up to now, while scarce data are available on other aspects, including physiology. The purpose of this study was to advance our understanding of the physiological differences between cave A. aquaticus and its surface-dwelling counterparts. We sampled two surface populations from the surface section of the sinking Pivka River (central Slovenia, Europe, i.e. locality Pivka Polje, and locality Planina Polje, and one cave population from the subterranean section of the sinking Pivka River, i.e. locality Planina Cave. Animals were sampled in spring, summer and autumn. We measured the activities of acetylcholinesterase (AChE and glutathione S-transferase (GST in individuals snap-frozen in the field immediately after collection. Acetylcholinesterase is likely related to animals' locomotor activity, while GST activity is related to the metabolic activity of an organism. Our study shows significantly lower AChE and GST activities in the cave population in comparison to both surface A. aquaticus populations. This confirms the assumption that cave A. aquaticus have lower locomotor and metabolic activity than surface A. aquaticus in their respective natural environments. In surface A. aquaticus populations, seasonal fluctuations in GST activity were observed, while these were less pronounced in individuals from the more stable cave environment. On the other hand, AChE activity was generally season-independent in all populations. To our knowledge, this is the first study of its kind conducted in A. aquaticus. Our results show that among closely related cave and surface A. aquaticus populations also physiological differences are present besides the morphological and genetic

Effect of thermal stress and water deprivation on the acetylcholinesterase activity of the pig brain and hypophyses

Science.gov (United States)

Adejumo, D. O.; Egbunike, G. N.

1988-06-01

The effects of direct exposure of boars to thermal stress for 1 h daily for 5 days and to acute water deprivation for 24 or 48 h were studied on the acetylcholinesterase (AChE) activity of porcine brain and hypophysial regions. Mean ambient temperatures, respiratory rates and rectal temperatures in the open were significantly higher than inside the pen. Heat stress induced a rise in AChE activities in the pons, cerebellum, amygdala, hippocampus, hypothalamus, mid-brain and medulla oblongata. However, no significant changes were observed in the cerebral cortex, adenohypophysis and neurohypophysis. Water deprivation significantly ( Pmedulla oblongata were comparable to the amygdala in this respect. The adenohypophysis and neurohypophysis were relatively unaffected.

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

Science.gov (United States)

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. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthesis and Biological Evaluation of Novel Jatrorrhizine Derivatives with Amino Groups Linked at the 3-Position as Inhibitors of Acetylcholinesterase

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Xiaofei Jiang

2017-01-01

Full Text Available Jatrorrhizine was considered as one of the active constituents of Coptis chinensis Franch. Herein, jatrorrhizine derivatives with substituted amino groups linked at the 3-position were designed, synthesized, and biologically evaluated as inhibitors of acetylcholinesterase. Jatrorrhizine derivatives inhibited the activity of acetylcholinesterase (AChE to a greater extent than the lead compound jatrorrhizine. All these jatrorrhizine derivatives were proved to be potent inhibitors of acetylcholinesterase (AChE with submicromolar IC50 values, but less sensitive to butyrylcholinesterase (BuChE, which suggests that these jatrorrhizine derivatives are selective for AChE/BuChE. Compound 3g gave the most potent inhibitor activity for AChE (IC50 = 0.301 μM, which is greater than the lead compound jatrorrhizine. All these results demonstrated that these jatrorrhizine derivatives are potential inhibitors for AChE.

Comparison of Chlorpyrifos-Oxon and Paraoxon Acetylcholinesterase Inhibition Dynamics: Potential role of a peripheral binding site

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Kousba, Ahmed A.; Sultatos, L G.; Poet, Torka S.; Timchalk, Chuck

2004-08-02

The primary mechanism of action for organophosphorus (OP) insecticides involves the inhibition of acetylcholinesterase (AChE) by oxygenated metabolites (oxons). This inhibition has been attributed to the phosphorylation of the serine hydroxyl group located in the active site of the AChE molecule. The rate of phosphorylation is described by the bimolecular inhibitory rate constant (ki), which has been utilized for quantification of OP inhibitory capacity. It has been previously proposed that a peripheral binding site exists on the AChE molecule, which when occupied, reduces the capacity of additional oxon molecules to phosphorylate the active site. The objective of the current study was to evaluate the interaction of chlorpyrifos oxon (CPO) and paraoxon (PO) with rat brain AChE using a modified Ellman assay in conjunction with a pharmacodynamic model to further assess the dynamics of AChE inhibition and the potential role of a peripheral binding site. The ki for AChE inhibition determined at oxon concentrations of 5 x 10{sup -4} 100 nM were 0.212 and 0.0216 nM-1h-1 for CPO and PO, respectively. The spontaneous reactivation rates of the inhibited AChE for CPO and PO were 0.087 and 0.078 h-1, respectively. In contrast, the ki estimated at a low oxon concentration (1 pM) were {approx} 1,000 and 10,000 -fold higher than those determined at high CPO and PO concentrations, respectively. At these low concentrations, the ki estimates were approximately similar for both CPO and PO (180 and 250 nM-1h-1, respectively). This implies that at low exposure concentrations, both oxons exhibited similar inhibitory potency in contrast to the marked difference exhibited at higher concentrations, which is consistent with the presence of a peripheral binding site on the AChE enzyme. These results support the potential importance of a secondary binding site associated with AChE kinetics, particularly at low environmentally relevant concentrations.

Tyrosinase inhibitory components from Aloe vera and their antiviral activity.

Science.gov (United States)

Kim, Jang Hoon; Yoon, Ju-Yeon; Yang, Seo Young; Choi, Seung-Kook; Kwon, Sun Jung; Cho, In Sook; Jeong, Min Hee; Ho Kim, Young; Choi, Gug Seoun

2017-12-01

A new compound, 9-dihydroxyl-2'-O-(Z)-cinnamoyl-7-methoxy-aloesin (1), and eight known compounds (2-9) were isolated from Aloe vera. Their structures were elucidated using 1D/2D nuclear magnetic resonance and mass spectra. Compound 9 exhibited reversible competitive inhibitory activity against the enzyme tyrosinase, with an IC 50 value of 9.8 ± 0.9 µM. A molecular simulation revealed that compound 9 interacts via hydrogen bonding with residues His244, Thr261, and Val283 of tyrosinase. Additionally, compounds 3 and 7 were shown by half-leaf assays to exhibit inhibitory activity towards Pepper mild mottle virus.

Acute administration of fenproporex increased acetylcholinesterase activity in brain of young rats

OpenAIRE

TEODORAK, BRENA P.; FERREIRA, GABRIELA K.; SCAINI, GISELLI; WESSLER, LETÍCIA B.; HEYLMANN, ALEXANDRA S.; DEROZA, PEDRO; VALVASSORI, SAMIRA S.; ZUGNO, ALEXANDRA I.; QUEVEDO, JOÃO; STRECK, EMILIO L.

2015-01-01

Fenproporex is the second most commonly amphetamine-based anorectic consumed worldwide; this drug is rapidly converted into amphetamine, in vivo, and acts by increasing dopamine levels in the synaptic cleft. Considering that fenproporex effects on the central nervous system are still poorly known and that acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine, the present study investigated the effects of acute...

SERUM ACETYLCHOLINESTERASE LEVEL IN THE PATIENTS OF OPIOID (BROWN SUGAR) DEPENDENCE

OpenAIRE

Shah, Nilesh; Dave, Kirti

1992-01-01

The authors compared the serum acetylcholinesterase level in the patients of brown sugar dependence and the normal volunteers. Significantly lower level of serum acetylcholinesterase was found in patients of brown sugar dependence.

Two new lignans from Saururus chinensis and their DGAT inhibitory activity.

Science.gov (United States)

Li, Na; Tuo, Zhen-Dong; Qi, Shi-Zhou; Xing, Shan-Shan; Lee, Hyun-Sun; Chen, Jian-Guang; Cui, Long

2015-03-01

Two new lignans were isolated from Saururus chinensis, along with eight known compounds. Their structures were elucidated on the basis of spectroscopic and physico-chemical analyses. All the isolates were evaluated for in vitro inhibitory activity against DGAT1 and DGAT2. Among them, compounds 2, 3, 5 and 7 were found to exhibit selective inhibitory activity on DGAT1 with IC50 values ranging from 44.3±1.5 to 87.5±1.3μM. Copyright © 2014 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

The cartilage protein melanoma inhibitory activity contributes to inflammatory arthritis

NARCIS (Netherlands)

Yeremenko, Nataliya; Härle, Peter; Cantaert, Tineke; van Tok, Melissa; van Duivenvoorde, Leonie M.; Bosserhoff, Anja; Baeten, Dominique

2014-01-01

Melanoma inhibitory activity (MIA) is a small chondrocyte-specific protein with unknown function. MIA knockout mice (MIA(-/-)) have a normal phenotype with minor microarchitectural alterations of cartilage. Our previous study demonstrated that immunodominant epitopes of MIA are actively presented in

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

International Nuclear Information System (INIS)

Kilbourn, Michael R.; Sherman, Phillip S.; Snyder, Scott E.

1999-01-01

Simplified methods for in vivo studies of acetylcholinesterase (AChE) activity in rodent brain were evaluated using N-[ 11 C]methylpiperidinyl propionate ([ 11 C]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 [ 11 C]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 [ 11 C]PMP are suitable for studies where alterations of the peripheral blood metabolism of the tracer are kept to a minimum

Polypyridylruthenium(II complexes exert in vitro and in vivo nematocidal activity and show significant inhibition of parasite acetylcholinesterases

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Madhu Sundaraneedi

2018-04-01

Full Text Available Over 4.5 billion people are at risk of infection with soil transmitted helminths and there are concerns about the development of resistance to the handful of frontline nematocides in endemic populations. We investigated the anti-nematode efficacy of a series of polypyridylruthenium(II complexes and showed they were active against L3 and adult stages of Trichuris muris, the rodent homologue of the causative agent of human trichuriasis, T. trichiura. One of the compounds, Rubb12-mono, which was among the most potent in its ability to kill L3 (IC50 = 3.1 ± 0.4 μM and adult (IC50 = 5.2 ± 0.3 μM stage worms was assessed for efficacy in a mouse model of trichuriasis by administering 3 consecutive daily oral doses of the drug 3 weeks post infection with the murine whipworm Trichuris muris. Mice treated with Rubb12-mono showed an average 66% reduction (P = 0.015 in faecal egg count over two independent trials. The drugs partially exerted their activity through inhibition of acetylcholinesterases, as worms treated in vitro and in vivo showed significant decreases in the activity of this class of enzymes. Our data show that ruthenium complexes are effective against T. muris, a model gastro-intestinal nematode and soil-transmitted helminth. Further, knowledge of the target of ruthenium drugs can facilitate modification of current compounds to identify analogues which are even more effective and selective against Trichuris and other helminths of human and veterinary importance. Keywords: Acetylcholinesterase, Trichuris muris, Ruthenium complex, Anthelmintic

Inhibitory noise

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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.

New Biflavonoids with α-Glucosidase and Pancreatic Lipase Inhibitory Activities from Boesenbergia rotunda

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Nutputsorn Chatsumpun

2017-10-01

Full Text Available Roots of Boesenbergia rotunda (L. Mansf. are prominent ingredients in the cuisine of several Asian countries, including Thailand, Malaysia, Indonesia, India, and China. An extract prepared from the roots of this plant showed strong inhibitory activity against enzymes α-glucosidase and pancreatic lipase and was subjected to chromatographic separation to identify the active components. Three new biflavonoids of the flavanone-chalcone type (9, 12, and 13 were isolated, along with 12 known compounds. Among the 15 isolates, the three new compounds showed stronger inhibitory activity against α-glucosidase than the drug acarbose but displayed lower pancreatic lipase inhibitory effect than the drug orlistat. The results indicated the potential of B. rotunda roots as a functional food for controlling after-meal blood glucose levels.

Improvement of ACE inhibitory activity of casein hydrolysate by Maillard reaction with xylose.

Science.gov (United States)

Hong, Xu; Meng, Jun; Lu, Rong-Rong

2015-01-01

The Maillard reaction is widely used to improve the functional properties or biological activities of food. The purpose of this study was to investigate the effect of the Maillard reaction on angiotensin I converting enzyme (ACE) inhibitory activity in a casein hydrolysate-xylose system. Two-step hydrolysis was used to prepare casein ACE inhibitory peptides. Maillard reaction products (MRPs) were prepared by heating hydrolyzed casein with xylose at pH 8.0, 110 °C for up to 16 h. The results showed that the content of free amino group decreased (P Maillard reaction (P reaction in the MRPs. The study shows that the Maillard reaction under appropriate conditions can improve the ACE inhibitory activity of casein hydrolysate effectively. © 2014 Society of Chemical Industry.

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

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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.

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

Science.gov (United States)

Yang, Yi; Nguyen, Thanh Thi; Jeong, Min-Hye; Crişan, Florin; Yu, Young Hyun; Ha, Hyung-Ho; Choi, Kyung Hee; Jeong, Hye Gwang; Jeong, Tae Cheon; Lee, Kwang Youl; Kim, Kyung Keun; Hur, Jae-Seoun; Kim, Hangun

2016-01-01

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. PMID:26751081

[Chemical Constituents from Leaves of Hibiscus syriacus and Their α-Glucosidase Inhibitory Activities].

Science.gov (United States)

Wei, Qiang; Ji, Xiao-ying; Xu, Fei; Li, Qian-rong; Yin, Hao

2015-05-01

To study the chemical constituents from Hibiscus syriacus leaves and their α-glucosidase inhibitory activities. Column chromatography including macroporous resins, silica gel and Sephadex LH-20 were used for the isolation and purification of all compounds. Spectroscopic methods including physical and chemical properties, 1H-NMR and 13C-NMR were used for the identification of structures. Their α-glucosidase inhibitory activities were detected by a 96-well microplate. 15 compounds were isolated and identified as β-sitosterol(1), β-daucostero (2), β-amyrin (3), oleanolic acid (4), stigmast-4-en-3-one (5), friedelin (6), syriacusin A (7), kaempferol (8), isovitexin (9), vitexin (10), apigenin (11), apigenin-7-O-β-D-glucopyranoside (12), luteolin-7-O-β-D-glucopyranoside (13), vitexin-7-O-β-D-glucopyranoside (14) and rutin (15). All the compounds are isolated from the leaves of Hibiscus syriacus for the first time. Taking acarbose as positive control, the α-glucosidase inhibitory activities of 15 compounds were evaluated. Compounds 7 and 9 have shown strong α-glucosidase inhibitory activities with IC50 of 39.03 ± 0.38 and 32.12 ± 0.62 mg/L, inhibition ratio of 94.95% and 97.15%, respectively.

Discrimination and Nitric Oxide Inhibitory Activity Correlation of Ajwa Dates from Different Grades and Origin

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Nur Ashikin Abdul-Hamid

2016-10-01

Full Text Available This study was aimed at examining the variations in the metabolite constituents of the different Ajwa grades and farm origins. It is also targeted at establishing the correlations between the metabolite contents and the grades and further to the nitric oxide (NO inhibitory activity. Identification of the metabolites was generated using 1H-NMR spectroscopy metabolomics analyses utilizing multivariate methods. The NO inhibitory activity was determined using a Griess assay. Multivariate data analysis, for both supervised and unsupervised approaches, showed clusters among different grades of Ajwa dates obtained from different farms. The compounds that contribute towards the observed separation between Ajwa samples were suggested to be phenolic compounds, ascorbic acid and phenylalanine. Ajwa dates were shown to have different metabolite compositions and exhibited a wide range of NO inhibitory activity. It is also revealed that Ajwa Grade 1 from the al-Aliah farm exhibited more than 90% NO inhibitory activity compared to the other grades and origins. Phenolic compounds were among the compounds that played a role towards the greater capacity of NO inhibitory activity shown by Ajwa Grade 1 from the al-Aliah farm.

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

International Nuclear Information System (INIS)

Rao, J.V.; Kavitha, P.

2004-01-01

The acute toxicity of azodrin (monocrotophos, an organophosphorus insecticide) was determined on a soil organism, Eisenia foetida. The median lethal concentrations (LC 50 ) were derived from a 48-h paper contact test and from artificial soil tests. The LC 50 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

Effects of carbofuran, diuron, and nicosulfuron on acetylcholinesterase activity in goldfish (Carassius auratus).

Science.gov (United States)

Bretaud, S; Toutant, J P; Saglio, P

2000-10-01

Juvenile goldfish (Carassius auratus) were exposed to three widely used pesticides; carbofuran, diuron, and nicosulfuron. Acetylcholinesterase (AChE) activity and molecular forms of AChE were first characterized in brain and skeletal muscle of unexposed fish. Skeletal muscle had higher AChE activity than brain (306 and 215 nmol/min/mg protein, respectively). In brain, four molecular forms of AChE were found: A12, G4, G2, and G1. In the muscle, three molecular forms were found A12, A8, and G2. AChE activity was then evaluated in both tissues of fish exposed to different concentration of pesticides (5, 50, and 500 microg/L) for 6, 12, 24, and 48 h. In brain, AChE activity was significantly inhibited during all the periods of exposure in response to 50 microg/L (19-28%) and 500 microg/L (85-87%) carbofuran. Such effect was observed in the muscle only at 500 microg/L (86-92%). Carbofuran had no effect on the distribution of molecular forms. Significant inhibitions (9-12%) of brain AChE activity were also observed in response to diuron and nicosulfuron at 500 microg/L during all periods of exposure and for 50 microg/L nicosulfuron after 24 and 48 h. This study pointed out short-term effects of exposure to sublethal concentrations of the three pesticides, ranging among different chemical families, on brain and muscle AChE in goldfish. Copyright 2000 Academic Press.

Surface display and bioactivity of Bombyx mori acetylcholinesterase on Pichia pastoris

Science.gov (United States)

To construct the Pichia pastoris (P. pastoris) cell surface display system of Bombyx mori acetylcholinesterase (BmAChE), the gene for the anchor protein (AGa1) was obtained from Saccharomyces cerevisiae and was fused with the modified Bombyx mori acetylcholinesterase gene (bmace) and transformed int...

Medicinal Plants and Their Inhibitory Activities against Pancreatic Lipase: A Review

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Atefehalsadat Seyedan

2015-01-01

Full Text Available Obesity is recognized as a major life style disorder especially in developing countries and it is prevailing at an alarming speed in new world countries due to fast food intake, industrialization, and reduction of physical activity. Furthermore, it is associated with a vast number of chronic diseases and disabilities. To date, relatively effective drugs, from either natural or synthetic sources, are generally associated with serious side effects, often leading to cessation of clinical trials or even withdrawal from the market. In order to find new compounds which are more effective or with less adverse effects compared to orlistat, the drug that has been approved for obesity, new compounds isolated from natural products are being identified and screened for antiobesity effects, in particular, for their pancreatic lipase inhibitory effect. Pancreatic lipase inhibitory activity has been extensively used for the determination of potential efficacy of natural products as antiobesity agents. In attempts to identify natural products for overcoming obesity, more researches have been focused on the identification of newer pancreatic lipase inhibitors with less unpleasant adverse effects. In this review, we consider the potential role of plants that have been investigated for their pancreatic lipase inhibitory activity.

Diethyl 2-(Phenylcarbamoylphenyl Phosphorothioates: Synthesis, Antimycobacterial Activity and Cholinesterase Inhibition

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Jarmila Vinšová

2014-05-01

Full Text Available A new series of 27 diethyl 2-(phenylcarbamoylphenyl phosphorothioates (thiophosphates was synthesized, characterized by NMR, IR and CHN analyses and evaluated against Mycobacterium tuberculosis H37Rv, Mycobacterium avium and two strains of Mycobacterium kansasii. The best activity against M. tuberculosis was found for O-{4-bromo-2-[(3,4-dichlorophenylcarbamoyl]phenyl} O,O-diethyl phosphorothioate (minimum inhibitory concentration of 4 µM. The highest activity against nontuberculous mycobacteria was exhibited by O-(5-chloro-2-{[4-(trifluoromethylphenyl]carbamoyl}-phenyl O,O-diethyl phosphorothioate with MIC values from 16 µM. Prepared thiophosphates were also evaluated against acetylcholinesterase from electric eel and butyrylcholinesterase from equine serum. Their inhibitory activity was compared to that of the known cholinesterases inhibitors galanthamine and rivastigmine. All tested compounds showed a higher (for AChE inhibition and comparable (for BChE inhibition activity to that of rivastigmine, with IC50s within the 8.04 to 20.2 µM range.

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

Energy Technology Data Exchange (ETDEWEB)

Kilbourn, Michael R. E-mail: mkilbour@umich.edu; Sherman, Phillip S.; Snyder, Scott E

1999-07-01

Simplified methods for in vivo studies of acetylcholinesterase (AChE) activity in rodent brain were evaluated using N-[{sup 11}C]methylpiperidinyl propionate ([{sup 11}C]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 [{sup 11}C]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 [{sup 11}C]PMP are suitable for studies where alterations of the peripheral blood metabolism of the tracer are kept to a minimum.

Two Step Synthesis of a Non-symmetric Acetylcholinesterase Reactivator

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Vit Koleckar

2007-08-01

Full Text Available The newly developed and very promising acetylcholinesterase reactivator (E-1- (2-hydroxyiminomethylpyridinium-4-(4-hydroxyiminomethylpyridinium-but-2-ene dibromide was prepared using two different pathways via a two-step synthesis involving the appropriate (E-1-(4-bromobut-2-enyl-2- or 4-hydroxyiminomethyl-pyridinium bromides. Afterwards, purities and yields of the desired product prepared by both routes were compared. Finally, its potency to reactivate several nerve agent-inhibited acetylcholinesterases was tested.

Quantitative structure-activity analysis of acetylcholinesterase inhibition by oxono and thiono analogues of organophosphorus compounds. (Reannouncement with new availability information)

Energy Technology Data Exchange (ETDEWEB)

Maxwell, D.M.; Brecht, K.M.

1992-02-01

A comparison of the bimolecular rate constants (ki) for inhibition of electric eel acetylcholinesterase (AChE) by the oxono (i.e., P=O) and thiono (i.e., P=S) analogues of parathion, methylparathion, leptophos, fonofos, sarin, and soman revealed that the oxono/thiono ratios of ki values varied from 14 for soman to 1240 for parathion. Analysis of the relative importance of the dissociation equilibrium constant and the phosphorylation rate constant in producing this variation in ki values indicated that the oxono analogues had phosphorylation rate constant values that varied in a narrow range from 8- to 14-fold greater than their thiono counterparts, while the oxono/thiono ratios for dissociation constants varied widely from 1 for soman to 82 for fonofos. The lower affinities of thiono analogues for AChE probably resulted from differences in the hydrophobic binding of oxono and thiono analogues to the active site of AChE, inasmuch as the hydrophobicities (i.e., octanol/water partition coefficients) of thiono organophosphorus compounds were much greater than the hydrophobicities of their oxono analogues. Quantitative structure-activity analysis indicated that the hydrophobic effects of oxono and thiono moieties correlated with log ki for AChE inhibition to a greater extent (r2 = 0.79) than their electronic effects (r2 equal to or less than 0.48). These observations suggest that the differences in hydrophobicity of oxono and thiono analogues of organophosphorus compounds may be as important as their electronic differences in determining their effectiveness as AChE inhibitors. Acetylcholinesterase, soman (GD), structure-activity analysis inhibition, oxono analogues, thiono analogues.

Inhibition of Acetylcholinesterase and Fatty Acid Composition in Theobroma grandiflorum Seeds

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Casandra Valentina Itriago

2017-07-01

Full Text Available Theobroma grandiflorum is an important fruit tree from Sterculiaceae family, native to the Brazilian Amazon, known in the region as cupuaçu. The seeds have a high fat content (24% with characteristics that resemble those of cocoa (Theobroma cacao butter with potential applications in the cosmetic, pharmaceutical and food industries. The main objective of this work was to explore the seed fats from T. grandiflorum that were analyzed for fatty acid composition by Gas Chromatography with Flame Ionization Detector (GC-FID and to analyze their activity for acetylcholinesterase inhibition. Chromatographic analysis provided detection of nine fatty acids. The major fatty acids found in the species were oleic (40.0%, stearic (32.7%, arachidic (10.4% and palmitic (8.0%. The acetylcholinesterase inhibition by fats from seeds was over 40.48%. DOI: http://dx.doi.org/10.17807/orbital.v0i0.894 

Evaluation of phenolic profile, enzyme inhibitory and antimicrobial activities of Nigella sativa L. seed extracts

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Anela Topcagic

2017-11-01

Full Text Available Black cumin (Nigella sativa L. [N.sativa] seed extracts demonstrated numerous beneficial biological effects including, among others, antidiabetic, anticancer, immunomodulatory, antimicrobial, anti-inflammatory, antihypertensive, and antioxidant activity. To better understand the phytochemical composition of N. sativa seeds, methanol seed extracts were analyzed for phenolic acid and flavonoid content. Furthermore, we tested N. sativa methanol, n-hexane, and aqueous seed extracts for their inhibitory activity against butyrylcholinesterase (BChE and catalase (CAT as well as for antimicrobial activity against several bacterial and a yeast strains. The phenolic content of N. sativa was analyzed using ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS. The inhibition of BChE was assessed by modified Ellman’s method, and the inhibition of CAT was determined by monitoring hydrogen peroxide consumption. The extracts were tested against Bacillus subtilis, Staphylococcus aureus, Salmonella enterica, and Escherichia coli using the agar diffusion method. The UHPLC-MS/MS method allowed the identification and quantification of 23 phenolic compounds within 15 minutes. The major components found in N. sativa seed extract were sinapinic acid (7.22 ± 0.73 µg/mg as a phenolic acid and kaempferol (11.74 ± 0.92 µg/mg as a flavonoid. All extracts showed inhibitory activity against BChE, with methanol seed extract demonstrating the highest inhibitory activity (inhibitory concentration 50% [IC50] 79.11 ± 6.06 µg/ml. The methanol seed extract also showed strong inhibitory activity against CAT with an IC50 value of 6.61 ± 0.27 µg/ml. Finally, the methanol extract exhibited considerable inhibitory activity against the tested microbial strains. Overall, this is the first study to investigate the ability of black cumin seed extracts to inhibit CAT. Our results indicate that N. sativa seed can be considered as an effective inhibitor

Effects of incentives, age, and behavior on brain activation during inhibitory control: A longitudinal fMRI study

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David J. Paulsen

2015-02-01

Full Text Available We investigated changes in brain function supporting inhibitory control under age-controlled incentivized conditions, separating age- and performance-related activation in an accelerated longitudinal design including 10- to 22-year-olds. Better inhibitory control correlated with striatal activation during neutral trials, while Age X Behavior interactions in the striatum indicated that in the absence of extrinsic incentives, younger subjects with greater reward circuitry activation successfully engage in greater inhibitory control. Age was negatively correlated with ventral amygdala activation during Loss trials, suggesting that amygdala function more strongly mediates bottom-up processing earlier in development when controlling the negative aspects of incentives to support inhibitory control. Together, these results indicate that with development, reward-modulated cognitive control may be supported by incentive processing transitions in the amygdala, and from facilitative to obstructive striatal function during inhibitory control.

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

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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.

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

Science.gov (United States)

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.

Preclinical and first-in-human evaluation of PRX-105, a PEGylated, plant-derived, recombinant human acetylcholinesterase-R

International Nuclear Information System (INIS)

Atsmon, Jacob; Brill-Almon, Einat; Nadri-Shay, Carmit; Chertkoff, Raul; Alon, Sari; Shaikevich, Dimitri; Volokhov, Inna; Haim, Kirsten Y.; Bartfeld, Daniel; Shulman, Avidor; Ruderfer, Ilya; Ben-Moshe, Tehila; Shilovitzky, Orit; Soreq, Hermona; Shaaltiel, Yoseph

2015-01-01

PRX-105 is a plant-derived recombinant version of the human ‘read-through’ acetylcholinesterase splice variant (AChE-R). Its active site structure is similar to that of the synaptic variant, and it displays the same affinity towards organophosphorus (OP) compounds. As such, PRX-105 may serve as a bio-scavenger for OP pesticides and chemical warfare agents. To assess its potential use in prophylaxis and treatment of OP poisoning we conducted several preliminary tests, reported in this paper. Intravenous (IV) PRX-105 was administered to mice either before or after exposure to an OP toxin. All mice who received an IV dose of 50 nmol/kg PRX-105, 2 min before being exposed to 1.33 × LD 50 and 1.5 × LD 50 of toxin and 10 min after exposure to 1.5 × LD 50 survived. The pharmacokinetic and toxicity profiles of PRX-105 were evaluated in mice and mini-pigs. Following single and multiple IV doses (50 to 200 mg/kg) no deaths occurred and no significant laboratory and histopathological changes were observed. The overall elimination half-life (t ½ ) in mice was 994 (± 173) min. Additionally, a first-in-human study, to assess the safety, tolerability and pharmacokinetics of the compound, was conducted in healthy volunteers. The t ½ in humans was substantially longer than in mice (average 26.7 h). Despite the small number of animals and human subjects who were assessed, the fact that PRX-105 exerts a protective and therapeutic effect following exposure to lethal doses of OP, its favorable safety profile and its relatively long half-life, renders it a promising candidate for treatment and prophylaxis against OP poisoning and warrants further investigation. - Highlights: • PRX-105 is a PEGylated plant-derived recombinant human acetylcholinesterase-R. • PRX-105 is a promising bio-scavenger for organophosphorous toxins at lethal doses. • PRX-105 was shown to protect animals both prophylactically and post-poisoning. • First-in-human study exhibited its safety

Preclinical and first-in-human evaluation of PRX-105, a PEGylated, plant-derived, recombinant human acetylcholinesterase-R

Energy Technology Data Exchange (ETDEWEB)

Atsmon, Jacob [Clinical Research Center, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University (Israel); Brill-Almon, Einat; Nadri-Shay, Carmit; Chertkoff, Raul; Alon, Sari [Protalix Biotherapeutics, Science Park, Carmiel (Israel); Shaikevich, Dimitri; Volokhov, Inna; Haim, Kirsten Y. [Clinical Research Center, Tel Aviv Sourasky Medical Center, Tel Aviv (Israel); Sackler Faculty of Medicine, Tel Aviv University (Israel); Bartfeld, Daniel [Protalix Biotherapeutics, Science Park, Carmiel (Israel); Shulman, Avidor, E-mail: avidors@protalix.com [Protalix Biotherapeutics, Science Park, Carmiel (Israel); Ruderfer, Ilya; Ben-Moshe, Tehila; Shilovitzky, Orit [Protalix Biotherapeutics, Science Park, Carmiel (Israel); Soreq, Hermona [Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem (Israel); Shaaltiel, Yoseph [Protalix Biotherapeutics, Science Park, Carmiel (Israel)

2015-09-15

PRX-105 is a plant-derived recombinant version of the human ‘read-through’ acetylcholinesterase splice variant (AChE-R). Its active site structure is similar to that of the synaptic variant, and it displays the same affinity towards organophosphorus (OP) compounds. As such, PRX-105 may serve as a bio-scavenger for OP pesticides and chemical warfare agents. To assess its potential use in prophylaxis and treatment of OP poisoning we conducted several preliminary tests, reported in this paper. Intravenous (IV) PRX-105 was administered to mice either before or after exposure to an OP toxin. All mice who received an IV dose of 50 nmol/kg PRX-105, 2 min before being exposed to 1.33 × LD{sub 50} and 1.5 × LD{sub 50} of toxin and 10 min after exposure to 1.5 × LD{sub 50} survived. The pharmacokinetic and toxicity profiles of PRX-105 were evaluated in mice and mini-pigs. Following single and multiple IV doses (50 to 200 mg/kg) no deaths occurred and no significant laboratory and histopathological changes were observed. The overall elimination half-life (t{sub ½}) in mice was 994 (± 173) min. Additionally, a first-in-human study, to assess the safety, tolerability and pharmacokinetics of the compound, was conducted in healthy volunteers. The t{sub ½} in humans was substantially longer than in mice (average 26.7 h). Despite the small number of animals and human subjects who were assessed, the fact that PRX-105 exerts a protective and therapeutic effect following exposure to lethal doses of OP, its favorable safety profile and its relatively long half-life, renders it a promising candidate for treatment and prophylaxis against OP poisoning and warrants further investigation. - Highlights: • PRX-105 is a PEGylated plant-derived recombinant human acetylcholinesterase-R. • PRX-105 is a promising bio-scavenger for organophosphorous toxins at lethal doses. • PRX-105 was shown to protect animals both prophylactically and post-poisoning. • First-in-human study

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

Science.gov (United States)

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

2016-11-01

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

Free Radical Scavenging and Alpha/Beta-glucosidases Inhibitory Activities of Rambutan (Nephelium lappaceum L. Peel Extract

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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

Antidotal effects of varthemia persica DC extract in organophosphate poisoning or warfare agents by measuring whole blood acetylcholinesterase

International Nuclear Information System (INIS)

Kalantari, H.; Siahapoosh, A.; Farsani, K. M.

2009-01-01

The organophosphates (ORPs) or war fare agents toxicity results from inhibition of acetylcholinesterase (AchE). phosphylation of the active serin of AchE leads to accumulation of acetylcholine in synaptic clefts leading to generalized cholinergic over-stimulation. Standard treatment of ORP poisoning includes a muscarinic antagonist such as Atropine, and acetylcholinesterase reactivator (oxime). Presently, oximes like abidoxime and pralidoxime are approved as antidotes against ORP poisoning but are considered to be rather ineffective against certain ORP. Like Soman. In this study, the protective effect of Varthemia persica DC extract on acetylcholinesterase was examined in rats. Animals in weight range of 200-225 g were divided in 8 groups. The negative control group received only 0.4 ml normal saline, reference group, received ethylparaoxone in dose of 50 percent of LD50, positive control group, received ethylparaoxone (50% LD50) and one minute later 50 mol of pralidoxime. Test group 1: received ethylparaoxone and one minute later single dose of methanolic extract of Varthemia persica (250 mg/kg), Test Group 2: daily received methanolic extract of V.persica (250 mg/kg) in six days and one minute after last dose of extract, ethylparaoxone (50% LD50) were injected, Test Group 3: received ethylparaoxone (50% LD50) and then six doses of methanolic extract of V.persica (250 mg/kg) in six continuous days. Test Group 4: received ethylparaoxone and then single dose of dichloromethane extract of V.persica (250 mg/kg). Test Group 5: received ethylparaoxone and one minute later single high dose of methanolic extract of V.persica (1000 mg/kg). Then blood withdrawn and acetylcholinesterase activity was measured according to modified Ellman's method. Only in groups which received extract of V. persica before and after injection of ethylparaoxone, the mean of acetylcholinesterase activity was significantly different with reference group (p 0.05) but no significant difference with

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

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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.

Chemometric profile, antioxidant and tyrosinase inhibitory activity of Camel's foot creeper leaves (Bauhinia vahlii).

Science.gov (United States)

Panda, Pritipadma; Dash, Priyanka; Ghosh, Goutam

2018-03-01

The present study is the first effort to a comprehensive evaluation of antityrosinase activity and chemometric analysis of Bauhinia vahlii. The experimental results revealed that the methanol extract of Bauhinia vahlii (BVM) possesses higher polyphenolic compounds and total antioxidant activity than those reported elsewhere for other more conventionally and geographically different varieties. The BVM contain saturated fatty acids such as hexadecanoic acid (10.15%), octadecanoic acid (1.97%), oleic acid (0.61%) and cis-vaccenic acid (2.43%) along with vitamin E (12.71%), α-amyrin (9.84%), methyl salicylate (2.39%) and β-sitosterol (17.35%), which were mainly responsible for antioxidant as well as tyrosinase inhibitory activity. Tyrosinase inhibitory activity of this extract was comparable to that of Kojic acid. These findings suggested that the B. vahlii leaves could be exploited as potential source of natural antioxidant and tyrosinase inhibitory agent, as well.

Inhibitory activity of a water-soluble morin derivative on phosphatase ...

African Journals Online (AJOL)

enoh

2012-03-01

Mar 1, 2012 ... E-mail: taipinghe@163.com. Tel: 86- ... anthraquinone compounds from Rubia akane show inhibitory activity on .... incubation of the cells at 37°C for 24 h, the phase contrast images ... inverted microscope (Olympus IX50).

Upregulation of α7 Nicotinic Receptors by Acetylcholinesterase C-Terminal Peptides

Science.gov (United States)

Bond, Cherie E.; Zimmermann, Martina; Greenfield, Susan A.

2009-01-01

Background The alpha-7 nicotinic acetylcholine receptor (α7-nAChR) is well known as a potent calcium ionophore that, in the brain, has been implicated in excitotoxicity and hence in the underlying mechanisms of neurodegenerative disorders such as Alzheimer's disease. Previous research implied that the activity of this receptor may be modified by exposure to a peptide fragment derived from the C-terminal region of the enzyme acetylcholinesterase. This investigation was undertaken to determine if the functional changes observed could be attributed to peptide binding interaction with the α7-nAChR, or peptide modulation of receptor expression. Methodology/Principal Findings This study provides evidence that two peptides derived from the C-terminus of acetylcholinesterase, not only selectively displace specific bungarotoxin binding at the α7-nAChR, but also alter receptor binding properties for its familiar ligands, including the alternative endogenous agonist choline. Of more long-term significance, these peptides also induce upregulation of α7-nAChR mRNA and protein expression, as well as enhancing receptor trafficking to the plasma membrane. Conclusions/Significance The results reported here demonstrate a hitherto unknown relationship between the α7-nAChR and the non-enzymatic functions of acetylcholinesterase, mediated independently by its C-terminal domain. Such an interaction may prove valuable as a pharmacological tool, prompting new approaches for understanding, and combating, the process of neurodegeneration. PMID:19287501

Lactobacillus crispatus dominant vaginal microbiome is associated with inhibitory activity of female genital tract secretions against Escherichia coli.

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Jeny P Ghartey

Full Text Available 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.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.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.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.

Characterization and biological significance of deacetylase

International Nuclear Information System (INIS)

Dipaola, E.A.

1985-01-01

An attempt is made to clarify the mechanism by which the one known deacetylase inhibitor, sodium butyrate, works and to identify other inhibitors of deacetylase activity. In doing so it was hoped to characterize the enzyme and to better understand its role in regulating genomic expression. The data showed that deacetylases not only showed activity toward their natural histone substrates, but also toward free acetyllysine and to a lesser degree toward acetylcholine, the latter being the natural substrate for acetylcholinesterases. Conversely, acetylcholinesterase was shown to be able to deacetylate groups from acetyllysine and acetylated histones. Decamethonium bromide, a well-known binder of acetylcholinesterase would not absorb the deacetylase. Diisopropylfluorophosphate (DFP), an anti-cholinesterase, exhibited no inhibitory effect on deacetylase activity, while acetylcholinesterase showed little or no sensitivity to butyrate inhibition. These findings along with the use of 3 H-DFP binding to fingerprint enzyme bands on gels became the basic criteria for distinguishing between deacetylase and acetylcholinesterase activity

Jojoba seed meal proteins associated with proteolytic and protease inhibitory activities.

Science.gov (United States)

Shrestha, Madan K; Peri, Irena; Smirnoff, Patricia; Birk, Yehudith; Golan-Goldhirsh, Avi

2002-09-25

The jojoba, Simmondsia chinensis, is a characteristic desert plant native to the Sonoran desert. The jojoba meal after oil extraction is rich in protein. The major jojoba proteins were albumins (79%) and globulins (21%), which have similar amino acid compositions and also showed a labile thrombin-inhibitory activity. SDS-PAGE showed two major proteins at 50 kDa and 25 kDa both in the albumins and in the globulins. The 25 kDa protein has trypsin- and chymotrypsin-inhibitory activities. In vitro digestibility of the globulins and albumins resembled that of casein and soybean protein concentrates and was increased after heat treatment. The increased digestibility achieved by boiling may be attributed to inactivation of the protease inhibitors and denaturation of proteins.

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

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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.

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

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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.

Neurofeedback Training Effects on Inhibitory Brain Activation in ADHD: A Matter of Learning?

Science.gov (United States)

Baumeister, Sarah; Wolf, Isabella; Holz, Nathalie; Boecker-Schlier, Regina; Adamo, Nicoletta; Holtmann, Martin; Ruf, Matthias; Banaschewski, Tobias; Hohmann, Sarah; Brandeis, Daniel

2018-05-15

Neurofeedback training (NF) is a promising non-pharmacological treatment for ADHD that has been associated with improvement of attention-deficit/hyperactivity disorder (ADHD)-related symptoms as well as changes in electrophysiological measures. However, the functional localization of neural changes following NF compared to an active control condition, and of successful learning during training (considered to be the critical mechanism for improvement), remains largely unstudied. Children with ADHD (N=16, mean age: 11.81, SD: 1.47) were randomly assigned to either slow cortical potential (SCP, n=8) based NF or biofeedback control training (electromyogram feedback, n=8) and performed a combined Flanker/NoGo task pre- and post-training. Effects of NF, compared to the active control, and of learning in transfer trials (approximating successful transfer to everyday life) were examined with respect to clinical outcome and functional magnetic resonance imaging (fMRI) changes during inhibitory control. After 20 sessions of training, children in the NF group presented reduced ADHD symptoms and increased activation in areas associated with inhibitory control compared to baseline. Subjects who were successful learners (n=9) also showed increased activation in an extensive inhibitory network irrespective of the type of training. Activation increased in an extensive inhibitory network following NF training, and following successful learning through NF and control biofeedback. Although this study was only powered to detect large effects and clearly requires replication in larger samples, the results suggest a crucial role for learning effects in biofeedback trainings. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Acetylcholinesterase and Butyrylcholinesterase Inhibited by Paraoxon

Czech Academy of Sciences Publication Activity Database

Kuča, K.; Musilová, L.; Paleček, J.; Církva, Vladimír; Paar, M.; Musílek, K.; Hrabinová, M.; Pohanka, M.; Zdarová Karasová, J.; Jun, D.

2009-01-01

Roč. 14, č. 12 (2009), s. 4915-4921 ISSN 1420-3049 Grant - others:MO0(CZ) FZV0000604 Institutional research plan: CEZ:AV0Z40720504 Keywords : acetylcholinesterase * reactivator * oxime Subject RIV: CC - Organic Chemistry Impact factor: 1.738, year: 2009

New Acetylcholinesterase Inhibitors for Alzheimer's Disease

Directory of Open Access Journals (Sweden)

Mona Mehta

2012-01-01

Full Text Available Acetylcholinesterase (AChE remains a highly viable target for the symptomatic improvement in Alzheimer's disease (AD because cholinergic deficit is a consistent and early finding in AD. The treatment approach of inhibiting peripheral AchE for myasthenia gravis had effectively proven that AchE inhibition was a reachable therapeutic target. Subsequently tacrine, donepezil, rivastigmine, and galantamine were developed and approved for the symptomatic treatment of AD. Since then, multiple cholinesterase inhibitors (ChEI continue to be developed. These include newer ChEIs, naturally derived ChEIs, hybrids, and synthetic analogues. In this paper, we summarize the different types of ChEIs in development and their respective mechanisms of actions. This pharmacological approach continues to be active with many promising compounds.

Optimization of sol-gel medium for entrapment of acetylcholinesterase enzyme in biosensor for pesticide detection

Science.gov (United States)

Wijayanti, S. D.; Rahayu, F. S.; Widyaningsih, T. D.

2018-03-01

Pesticides are chemical substances used to kill and control pests or diseases that can damage crops. The use of pesticides should be done precisely because the accumulation of chemicals contained in pesticides can cause various health effects. Therefore, detection of pesticide residues on plants is important to reduce the risk of poisoning due to pesticide residues. Some of the conventional methods that have been done to detect pesticide residues have weaknesses among expensive tools, takes a long time, and are generally performed by trained laboratory technicians. Biosensors are analytical devices that can measure the quantitative or semi-quantitative targets of analyte by utilizing a bioreceptor such as enzyme. Several studies have shown that enzyme-based acetylcholinesterase-based biosensors can be used to detect pesticide residues in vegetable samples. The objective of this research was to get a proper silica based sol-gel formulation with molar ratio of H2O:TEOS and NaOH concentration as immobilization medium of acetylcholinesterase enzyme for biosensor application. Response Surface Methodology (RSM) was used in order to determine the interaction between the parameters studied and resulting responses which were amount and activity of acetylcholinesterase enzyme. Based on the research, the best result for immobilized enzyme activity was shown by molar ratio (H2O: TEOS) 1: 8 and 4 mM NaOH treatment.

Neuroprotective effect of seaweeds inhabiting South Indian coastal area (Hare Island, Gulf of Mannar Marine Biosphere Reserve): Cholinesterase inhibitory effect of Hypnea valentiae and Ulva reticulata.

Science.gov (United States)

Suganthy, N; Karutha Pandian, S; Pandima Devi, K

2010-01-14

Alzheimer's disease (AD) is the most common form of dementia, which is one of the four leading causes of death in developed nations. Until date the only symptomatic treatment for this disease is based on the "cholinergic hypothesis" where the drugs enhance acetylcholine levels in the brain by inhibiting acetylcholinesterase (AChE). In the course for screening cholinesterase inhibitors about eight seaweeds, with wide pharmaceutical applications, were collected from Hare Island, Gulf of Mannar, Marine Biosphere Reserve, Tamil Nadu, India. Inhibitory effect of methanol extract of the seaweeds was studied in vitro by incubating various concentration of the extract with AChE or butyryl cholinesterase (BuChE) and assessing their activities by Ellman's colorimetric method. Kinetic parameters like IC(50), K(i) and V(max) were also analyzed. The results showed that of the eight seaweeds screened Hypnea valentiae, Padina gymnospora, Ulva reticulata and Gracilaria edulis exhibited inhibitory activity to AChE with IC(50) value of 2.6, 3.5, 10 and 3mg/ml respectively, while H. valentiae, Enteromorpha intestinalis, Dictyota dichotoma and U. reticulata showed 50% inhibition to BuChE at concentration 3.9, 7, 6.5 and 10mg/ml respectively. The inhibitory activities of the seaweed extracts were comparable to the standard drug donepezil. Enzyme kinetic analysis showed that algal extracts exhibited mixed type inhibition (partial noncompetitive inhibition). Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Tyrosinase Inhibitory and Antioxidant Activities of Silk Cocoons and Mulberry Leaves

International Nuclear Information System (INIS)

Thongphasuk, Jarunee; Thongphasuk, Piyanuch

2005-10-01

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

Tyrosinase Inhibitory and Antioxidant Activities of Silk Cocoons and Mulberry Leaves

Energy Technology Data Exchange (ETDEWEB)

Thongphasuk, Jarunee [Office of Atoms for Peace, Bangkok (Thailand); Thongphasuk, Piyanuch [Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Rangsit University, Pathumthani (Thailand)

2005-10-15

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 {mu}g/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 {mu}g/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.

Absolute Configurations and NO Inhibitory Activities of Terpenoids from Curcuma longa.

Science.gov (United States)

Xu, Jing; Ji, Feifei; Kang, Jing; Wang, Hao; Li, Shen; Jin, Da-Qing; Zhang, Qiang; Sun, Hongwei; Guo, Yuanqiang

2015-06-24

Curcuma longa L., belonging to the Zingiberaceae family, is a perennial herb and has been used as a spice and a pigment in the food industry. In the ongoing search for inhibitory reagents of NO production and survey of the chemical composition of natural vegetable foods, the chemical constituents of C. longa used as spice were investigated. This investigation resulted in the isolation of 2 new terpenoids and 14 known analogues. Their structures were established on the basis of the extensive analyses of 1D and 2D NMR spectroscopic data, and the absolute configurations of 1-4 were elucidated by comparison of the calculated and experimental ECD spectra. Among them, compound 1 is a rare norditerpene with an ent-labdane skeleton, and 2 is a skeletally novel sesquiterpene having an eight-membered ring. All of the compounds were found to possess NO inhibitory activities in murine microglial BV-2 cells. The discovery of two new compounds in this chemical investigation further disclosed the chemical composition of C. longa used a food spice, and the bioassay implied that the natural food spice C. longa, containing terpenoids with NO inhibitory activities, may be potentially promotive to human health.

Larvicides and acetylcholinesterase inhibitors from Kalanchoe species

International Nuclear Information System (INIS)

Trevisan, Maria Teresa Salles; Bezerra, Maria Zeneide Barbosa; Santiago, Gilvandete Maria Pinheiro; Feitosa, Chistiane Mendes; Verpoorte, Robert; Gorlaeus Laboratories, Leiden; Braz Filho, Raimundo

2006-01-01

Acetylcholine esterase inhibitors are successfully used to treat the symptoms of Alzheimer's disease. Extracts of three Kalanchoe species (K. brasiliensis, K. pinnata and K. gastonis-bornieri) showed acetylcholine esterase inhibitory effects and a toxic effect on Aedes aegypti larvae. Here we describe the bioassay guided fractionation of extracts of the most active extracts (K. brasiliensis) which resulted in the isolation of an active mixture of three flavonoids: 8-methoxyquercetin, 3,7-di-O-rhamnopyranoside and 8-methoxykaempferol-3,7-di-O-rhamnopyranoside. On TLC these flavonoids showed an acetylcholine esterase inhibitory effect. (author)

In vitro biological activity of Salvia leriifolia benth essential oil relevant to the treatment of Alzheimer's disease.

Science.gov (United States)

Loizzo, Monica Rosa; Menichini, Federica; Tundis, Rosa; Bonesi, Marco; Conforti, Filomena; Nadjafi, Farsad; Statti, Giancarlo Antonio; Frega, Natale Giuseppe; Menichini, Francesco

2009-01-01

In this study the chemical composition, cholinesterase inhibitory property and anti-inflammatory activity of S. leriifolia Benth. essential oil was evaluated for the first time. GC and GC-MS analysis revealed the presence of camphor (10.5%), 1,8-cineole (8.6%), camphene (6.2%) and alpha-pinene (4.7%) as main constituents. S. leriifolia oil exhibited a promising antioxidant activity by DPPH assay with an IC(50) 2.26 microL/mL. Interesting cholinesterase inhibitory activity was also found with IC(50) values of 0.32 and 0.29 microL/mL for acetylcholinesterase (AChE) and butyrrylcholinesterase (BChE), respectively. Moreover, this oil inhibited LPS-induced NO production with an IC(50) value of 165 microg/mL. The absence of cytotoxicity at 1000 microg/mL was evaluated by MTT assay in 142BR cells.

Pacemaker activity and inhibitory neurotransmission in the colon of Ws/Ws mutant rats

DEFF Research Database (Denmark)

Albertí, Elena; Mikkelsen, Hanne Birte; Wang, Xuanyu

2007-01-01

The aim of this study was to characterize the pacemaker activity and inhibitory neurotransmission in the colon of Ws/Ws mutant rats, which harbor a mutation in the c-kit gene that affects development of interstitial cells of Cajal (ICC). In Ws/Ws rats, the density of KIT-positive cells was markedly...... as indirect innervation via ICC. In summary, loss of ICC markedly affects pacemaker and motor activities of the rat colon. Inhibitory innervation is largely maintained but nitrergic innervation is reduced possibly related to the loss of ICC-mediated relaxation....

Effects of Different Working Modes of Ultrasound on Structural Characteristics of Zein and ACE Inhibitory Activity of Hydrolysates

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Xiaofeng Ren

2017-01-01

Full Text Available Ultrasound was used as a new technology to pretreat protein prior to proteolysis to improve enzymolysis efficiency. The effects of different working modes of ultrasound on the angiotensin I-converting enzyme (ACE inhibitory activity of zein hydrolysates and the structural characteristics of zein were investigated. The solubility, surface hydrophobicity (H0, ultraviolet-visible (UV-Vis spectra, intrinsic fluorescence spectra, and circular dichroism (CD spectra of zein pretreated with ultrasound were determined. All ultrasound pretreatments significantly improved the ACE inhibitory activity of zein hydrolysates (p<0.05. The highest ACE inhibitory activity, representing an increase of 99.21% over the control, was obtained with dual sweeping frequency ultrasound of 33±2 and 68±2 kHz. The effects of single sweeping frequency and dual fixed frequency ultrasound were stronger than those of single fixed frequency ultrasound for improving the ACE inhibitory activity of zein. Structural changes in zein were induced by ultrasound, as confirmed by changes in the solubility, H0, UV-Vis spectra, intrinsic fluorescence spectra, and CD spectra of zein, and these were consistent with the corresponding ACE inhibitory activities of zein hydrolysates. Thus, ultrasound working mode and frequency have significant effects on the structure of zein and the ACE inhibitory activity of zein hydrolysates.

2-Aryl benzimidazoles: Synthesis, In vitro α-amylase inhibitory activity, and molecular docking study.

Science.gov (United States)

Adegboye, Akande Akinsola; Khan, Khalid Mohammed; Salar, Uzma; Aboaba, Sherifat Adeyinka; Kanwal; Chigurupati, Sridevi; Fatima, Itrat; Taha, Mohammad; Wadood, Abdul; Mohammad, Jahidul Isalm; Khan, Huma; Perveen, Shahnaz

2018-04-25

Despite of many diverse biological activities exhibited by benzimidazole scaffold, it is rarely explored for the α-amylase inhibitory activity. For that purpose, 2-aryl benzimidazole derivatives 1-45 were synthesized and screened for in vitro α-amylase inhibitory activity. Structures of all synthetic compounds were deduced by various spectroscopic techniques. All compounds revealed inhibition potential with IC 50 values of 1.48 ± 0.38-2.99 ± 0.14 μM, when compared to the standard acarbose (IC 50  = 1.46 ± 0.26 μM). Limited SAR suggested that the variation in the inhibitory activities of the compounds are the result of different substitutions on aryl ring. In order to rationalize the binding interactions of most active compounds with the active site of α-amylase enzyme, in silico study was conducted. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Discrete Fourier Transform-Based Multivariate Image Analysis: Application to Modeling of Aromatase Inhibitory Activity.

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Barigye, Stephen J; Freitas, Matheus P; Ausina, Priscila; Zancan, Patricia; Sola-Penna, Mauro; Castillo-Garit, Juan A

2018-02-12

We recently generalized the formerly alignment-dependent multivariate image analysis applied to quantitative structure-activity relationships (MIA-QSAR) method through the application of the discrete Fourier transform (DFT), allowing for its application to noncongruent and structurally diverse chemical compound data sets. Here we report the first practical application of this method in the screening of molecular entities of therapeutic interest, with human aromatase inhibitory activity as the case study. We developed an ensemble classification model based on the two-dimensional (2D) DFT MIA-QSAR descriptors, with which we screened the NCI Diversity Set V (1593 compounds) and obtained 34 chemical compounds with possible aromatase inhibitory activity. These compounds were docked into the aromatase active site, and the 10 most promising compounds were selected for in vitro experimental validation. Of these compounds, 7419 (nonsteroidal) and 89 201 (steroidal) demonstrated satisfactory antiproliferative and aromatase inhibitory activities. The obtained results suggest that the 2D-DFT MIA-QSAR method may be useful in ligand-based virtual screening of new molecular entities of therapeutic utility.

Inhibitory activity of tryptanthrin on prostaglandin and leukotriene synthesis.

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Danz, Henning; Stoyanova, Stefka; Thomet, Olivier A R; Simon, Hans-Uwe; Dannhardt, Gerd; Ulbrich, Holger; Hamburger, Matthias

2002-10-01

The indolo[2,1- b]quinazoline alkaloid tryptanthrin has previously been identified as the cyclooxygenase-2 (COX-2) inhibitory principle in the extract ZE550 prepared from the medicinal plant Isatis tinctoria (Brassicaceae). We here investigated the potential inhibitory activity of tryptanthrin and ZE550 on COX-2, COX-1 in cellular and cell-free systems. A certain degree of selectivity towards COX-2 was observed when COX-1-dependent formation of thromboxane B(2) (TxB(2)) in HEL cells and COX-2-dependent formation of 6-ketoprostaglandin F(1alpha) (6-keto-PGF(1alpha)) in Mono Mac 6 and RAW 264.7 cells were compared. Preferential inhibition of COX-2 by two orders of magnitude was found in phorbol myristate acetate (PMA) activated bovine aortic coronary endothelial cells (BAECs). Assays with purified COX isoenzymes from sheep confirmed the high selectivity towards COX-2. The leukotriene B(4) (LTB(4)) release from calcium ionophore-stimulated human granulocytes (neutrophils) was used as a model to determine 5-lipoxygenase (5-LOX) activity. Tryptanthrin and the extract ZE550 inhibited LTB(4) release in a dose dependent manner and with a potency comparable to that of the clinically used 5-LOX inhibitor zileuton.

A novel class of thiosemicarbazones show multi-functional activity for the treatment of Alzheimer's disease.

Science.gov (United States)

Palanimuthu, Duraippandi; Poon, Rachal; Sahni, Sumit; Anjum, Rukhsana; Hibbs, David; Lin, Hsuan-Yu; Bernhardt, Paul V; Kalinowski, Danuta S; Richardson, Des R

2017-10-20

Over 44 million people live with Alzheimer's disease (AD) worldwide. Currently, only symptomatic treatments are available for AD and no cure exists. Considering the lack of effective treatments for AD due to its multi-factorial pathology, development of novel multi-target-directed drugs are desirable. Herein, we report the development of a novel series of thiosemicarbazones derived from 1-benzylpiperidine, a pharmacophore within the acetylcholinesterase inhibitor, Donepezil. These thiosemicarbazones were designed to target five major AD hallmarks, including: low acetylcholine levels, dysfunctional autophagy, metal dys-homeostasis, protein aggregation and oxidative stress. Of these thiosemicarbazones, pyridoxal 4-N-(1-benzylpiperidin-4-yl)thiosemicarbazone (PBPT) emerged as the lead compound. This agent demonstrated the most promising multi-functional activity by exhibiting very low anti-proliferative activity, substantial iron chelation efficacy, inhibition of copper-mediated amyloid-β aggregation, inhibition of oxidative stress, moderate acetylcholinesterase inhibitory activity and autophagic induction. These diverse properties highlight the potential of the lead ligand, PBPT, as a promising multi-functional agent for AD treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

B16-BL6 melanoma cells release inhibitory factor(s) of active pump activity in isolated lymph vessels.

Science.gov (United States)

Nakaya, K; Mizuno, R; Ohhashi, T

2001-12-01

We investigated whether supernatant cultured with melanoma cell lines B16-BL6 and K1735 or the Lewis lung carcinoma cell line (LLC) can regulate lymphatic pump activity with bioassay preparations isolated from murine iliac lymph vessels. B16-BL6 and LLC supernatants caused significant dilation of lymph microvessels with cessation of pump activity. B16-BL6 supernatant produced dose-related cessation of lymphatic pump activity. There was no significant tachyphylaxis in the supernatant-mediated inhibitory response of lymphatic pump activity. Pretreatment with 3 x 10(-5) M N(omega)-nitro-L-arginine methyl ester (L-NAME) or 10(-7) M or 10(-6) M glibenclamide and 5 x 10(-4) M 5-hydroxydecanoic acid caused significant reduction of supernatant-mediated inhibitory responses. Simultaneous treatment with 10(-3) M L-arginine and 3 x 10(-5) M L-NAME significantly lessened L-NAME-induced inhibition of the supernatant-mediated response, suggesting that endogenous nitric oxide (NO) plays important roles in supernatant-mediated inhibitory responses. Chemical treatment dialyzed substances of B16-BL6 cells may release nonpeptide substance(s) of <1,000 MW, resulting in significant cessation of lymphatic pump activity via production and release of endogenous NO and activation of mitochondrial ATP-sensitive K(+) channels.

Diverse models for the prediction of CDK4 inhibitory activity of ...

Indian Academy of Sciences (India)

employed for development of models for the prediction of CDK4 inhibitory activity using a dataset comprising of 52 analogues of ... index; molecular connectivity index; connective eccentricity topochemical index. 1. ... 80% of human cancers.

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

Institute of Scientific and Technical Information of China (English)

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.

2-(2-Pyridyl) Benzimidazole Analogs and their beta-Glucuronidase Inhibitory Activity

International Nuclear Information System (INIS)

Kamil, A.; Noureen, S.

2015-01-01

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)

Acetylcholinesterase activity, cohabitation with floricultural workers, and blood pressure in Ecuadorian children.

Science.gov (United States)

Suarez-Lopez, Jose R; Jacobs, David R; Himes, John H; Alexander, Bruce H

2013-05-01

Acetylcholinesterase (AChE) inhibitors are commonly used pesticides that can effect hemodynamic changes through increased cholinergic stimulation. Children of agricultural workers are likely to have paraoccupational exposures to pesticides, but the potential physiological impact of such exposures is unclear. We investigated whether secondary pesticide exposures were associated with blood pressure and heart rate among children living in agricultural Ecuadorian communities. This cross-sectional study included 271 children 4-9 years of age [51% cohabited with one or more flower plantation workers (mean duration, 5.2 years)]. Erythrocyte AChE activity was measured using the EQM Test-mate system. Linear regression models were used to estimate associations of systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate with AChE activity, living with flower workers, duration of cohabitation with a flower worker, number of flower workers in the child's home, and number of practices that might increase children's exposure to pesticides. Mean (± SD) AChE activity was 3.14 ± 0.49 U/mL. A 1-U/mL decrease in AChE activity was associated with a 2.86-mmHg decrease in SBP (95% CI: -5.20, -0.53) and a 2.89-mmHg decrease in DBP (95% CI: -5.00, -0.78), after adjustment for potential confounders. Children living with flower workers had lower SBP (-1.72 mmHg; 95% CI: -3.53, 0.08) than other children, and practices that might increase exposure also were associated with lower SBP. No significant associations were found between exposures and heart rate. Our findings suggest that subclinical secondary exposures to pesticides may affect vascular reactivity in children. Additional research is needed to confirm these findings.

Butyryl- and acetyl-cholinesterase inhibitory activities in essential oils of Salvia species and their constituents.

Science.gov (United States)

Savelev, Sergey U; Okello, Edward J; Perry, Elaine K

2004-04-01

Extracts of Salvia (sage) species have been reported to have cholinergic activities relevant to the treatment of Alzheimer's disease. A lack of information on the inhibition of the enzyme butyrylcholinesterase, also considered to be a target in the treatment of the disease, prompted this in vitro investigation of the essential oils of S. fruticosa, S. lavandulaefolia, S. of ficinalis and S. of ficinalis var. purpurea for anti-butyrylcholinesterase activity. Dose-dependent inhibition of human cholinesterases by the extracts and constituents was determined using the method of Ellman. A time dependent increase in the inhibition of butyrylcholinesterase by the oils of S. fruticosa and S. of ficinalis var. purpurea was evident. IC(50) values decreased from 0.15 +/- 0.007 and 0.14 +/- 0.007 mg/mL after 5 min to 0.035 +/- 0.016 and 0.06 +/- 0.018 mg/mL after 90 min incubation time respectively. The slow onset of inhibition of butyrylcholinesterase was also shown by individual constituents, such as 3-carene and beta-pinene. Analyses of the chemical composition of the oils and anti-butyrylcholinesterase activity of their constituents revealed that none of the compounds tested would account for the total activity of the oils and that synergy is likely. Copyright 2004 John Wiley & Sons, Ltd.

Molecular evaluation of herbal compounds as potent inhibitors of acetylcholinesterase for the treatment of Alzheimer's disease.

Science.gov (United States)

Chen, Yan-Xiu; Li, Guan-Zeng; Zhang, Bin; Xia, Zhang-Yong; Zhang, Mei

2016-07-01

Alzheimer's disease (AD) is a progressive disease and the predominant cause of dementia. Common symptoms include short-term memory loss, and confusion with time and place. Individuals with AD depend on their caregivers for assistance, and may pose a burden to them. The acetylcholinesterase (AChE) enzyme is a key target in AD and inhibition of this enzyme may be a promising strategy in the drug discovery process. In the present study, an inhibitory assay was carried out against AChE using total alkaloidal plants and herbal extracts commonly available in vegetable markets. Subsequently, molecular docking simulation analyses of the bioactive compounds present in the plants were conducted, as well as a protein‑ligand interaction analysis. The stability of the docked protein‑ligand complex was assessed by 20 ns molecular dynamics simulation. The inhibitory assay demonstrated that Uncaria rhynchophylla and Portulaca oleracea were able to inhibit AChE. In addition, molecular docking simulation analyses indicated that catechin present in Uncaria rhynchophylla, and dopamine and norepinephrine present in Portulaca oleracea, had the best docking scores and interaction energy. In conclusion, catechin in Uncaria rhynchophylla, and dopamine and norepinephrine in Portulaca oleracea may be used to treat AD.

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

Directory of Open Access Journals (Sweden)

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.

Distribution of intravenously administered acetylcholinesterase inhibitor and acetylcholinesterase activity in the adrenal gland: 11C-donepezil PET study in the normal rat.

Science.gov (United States)

Watabe, Tadashi; Naka, Sadahiro; Ikeda, Hayato; Horitsugi, Genki; Kanai, Yasukazu; Isohashi, Kayako; Ishibashi, Mana; Kato, Hiroki; Shimosegawa, Eku; Watabe, Hiroshi; Hatazawa, Jun

2014-01-01

Acetylcholinesterase (AChE) inhibitors have been used for patients with Alzheimer's disease. However, its pharmacokinetics in non-target organs other than the brain has not been clarified yet. The purpose of this study was to evaluate the relationship between the whole-body distribution of intravenously administered (11)C-Donepezil (DNP) and the AChE activity in the normal rat, with special focus on the adrenal glands. The distribution of (11)C-DNP was investigated by PET/CT in 6 normal male Wistar rats (8 weeks old, body weight  = 220 ± 8.9 g). A 30-min dynamic scan was started simultaneously with an intravenous bolus injection of (11)C-DNP (45.0 ± 10.7 MBq). The whole-body distribution of the (11)C-DNP PET was evaluated based on the Vt (total distribution volume) by Logan-plot analysis. A fluorometric assay was performed to quantify the AChE activity in homogenized tissue solutions of the major organs. The PET analysis using Vt showed that the adrenal glands had the 2nd highest level of (11)C-DNP in the body (following the liver) (13.33 ± 1.08 and 19.43 ± 1.29 ml/cm(3), respectively), indicating that the distribution of (11)C-DNP was the highest in the adrenal glands, except for that in the excretory organs. The AChE activity was the third highest in the adrenal glands (following the small intestine and the stomach) (24.9 ± 1.6, 83.1 ± 3.0, and 38.5 ± 8.1 mU/mg, respectively), indicating high activity of AChE in the adrenal glands. We demonstrated the whole-body distribution of (11)C-DNP by PET and the AChE activity in the major organs by fluorometric assay in the normal rat. High accumulation of (11)C-DNP was observed in the adrenal glands, which suggested the risk of enhanced cholinergic synaptic transmission by the use of AChE inhibitors.

Distribution of intravenously administered acetylcholinesterase inhibitor and acetylcholinesterase activity in the adrenal gland: 11C-donepezil PET study in the normal rat.

Directory of Open Access Journals (Sweden)

Tadashi Watabe

Full Text Available PURPOSE: Acetylcholinesterase (AChE inhibitors have been used for patients with Alzheimer's disease. However, its pharmacokinetics in non-target organs other than the brain has not been clarified yet. The purpose of this study was to evaluate the relationship between the whole-body distribution of intravenously administered (11C-Donepezil (DNP and the AChE activity in the normal rat, with special focus on the adrenal glands. METHODS: The distribution of (11C-DNP was investigated by PET/CT in 6 normal male Wistar rats (8 weeks old, body weight  = 220 ± 8.9 g. A 30-min dynamic scan was started simultaneously with an intravenous bolus injection of (11C-DNP (45.0 ± 10.7 MBq. The whole-body distribution of the (11C-DNP PET was evaluated based on the Vt (total distribution volume by Logan-plot analysis. A fluorometric assay was performed to quantify the AChE activity in homogenized tissue solutions of the major organs. RESULTS: The PET analysis using Vt showed that the adrenal glands had the 2nd highest level of (11C-DNP in the body (following the liver (13.33 ± 1.08 and 19.43 ± 1.29 ml/cm(3, respectively, indicating that the distribution of (11C-DNP was the highest in the adrenal glands, except for that in the excretory organs. The AChE activity was the third highest in the adrenal glands (following the small intestine and the stomach (24.9 ± 1.6, 83.1 ± 3.0, and 38.5 ± 8.1 mU/mg, respectively, indicating high activity of AChE in the adrenal glands. CONCLUSIONS: We demonstrated the whole-body distribution of (11C-DNP by PET and the AChE activity in the major organs by fluorometric assay in the normal rat. High accumulation of (11C-DNP was observed in the adrenal glands, which suggested the risk of enhanced cholinergic synaptic transmission by the use of AChE inhibitors.

Evaluation of Selected Culinary-Medicinal Mushrooms for Antioxidant and ACE Inhibitory Activities

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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.

Evaluation of Selected Culinary-Medicinal Mushrooms for Antioxidant and ACE Inhibitory Activities

Science.gov (United States)

Abdullah, Noorlidah; Ismail, Siti Marjiana; Aminudin, Norhaniza; Shuib, Adawiyah Suriza; Lau, Beng Fye

2012-01-01

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. PMID:21716693

Rosmarinus officinalis L. leaf extract improves memory impairment and affects acetylcholinesterase and butyrylcholinesterase activities in rat brain.

Science.gov (United States)

Ozarowski, Marcin; Mikolajczak, Przemyslaw L; Bogacz, Anna; Gryszczynska, Agnieszka; Kujawska, Malgorzata; Jodynis-Liebert, Jadwiga; Piasecka, Anna; Napieczynska, Hanna; Szulc, Michał; Kujawski, Radoslaw; Bartkowiak-Wieczorek, Joanna; Cichocka, Joanna; Bobkiewicz-Kozlowska, Teresa; Czerny, Boguslaw; Mrozikiewicz, Przemyslaw M

2013-12-01

Rosmarinus officinalis L. leaf as part of a diet and medication can be a valuable proposal for the prevention and treatment of dementia. The aim of the study was to assess the effects of subchronic (28-fold) administration of a plant extract (RE) (200 mg/kg, p.o.) on behavioral and cognitive responses of rats linked with acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity and their mRNA expression level in the hippocampus and frontal cortex. The passive avoidance test results showed that RE improved long-term memory in scopolamine-induced rats. The extract inhibited the AChE activity and showed a stimulatory effect on BuChE in both parts of rat brain. Moreover, RE produced a lower mRNA BuChE expression in the cortex and simultaneously an increase in the hippocampus. The study suggests that RE led to improved long-term memory in rats, which can be partially explained by its inhibition of AChE activity in rat brain. © 2013. Published by Elsevier B.V. All rights reserved.

JMBR VOLUME 14 Number 2.cdr

African Journals Online (AJOL)

FINEPRINT

Acute poisoning with typically HgCl 2 generally targets ... abdominal pain, vomiting, and bloody diarrhoea with ... concomitant occupational exposure to mercury ... activity of superoxide dismutase, catalase ..... Acetylcholinesterase Inhibitory,.

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

Energy Technology Data Exchange (ETDEWEB)

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.

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

International Nuclear Information System (INIS)

Mazzia, Christophe; Capowiez, Yvan; Sanchez-Hernandez, Juan C.; Koehler, Heinz-R.; Triebskorn, Rita; Rault, Magali

2011-01-01

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.

Angiotensin-I Converting Enzyme (ACE Inhibitory and Anti-Oxidant Activities of Sea Cucumber (Actinopyga lecanora Hydrolysates

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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.

High Efficiency Acetylcholinesterase Immobilization on DNA Aptamer Modified Surfaces

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Orada Chumphukam

2014-04-01

Full Text Available We report here the in vitro selection of DNA aptamers for electric eel acetylcholinesterase (AChE. One selected aptamer sequence (R15/19 has a high affinity towards the enzyme (Kd = 157 ± 42 pM. Characterization of the aptamer showed its binding is not affected by low ionic strength (~20 mM, however significant reduction in affinity occurred at high ionic strength (~1.2 M. In addition, this aptamer does not inhibit the catalytic activity of AChE that we exploit through immobilization of the DNA on a streptavidin-coated surface. Subsequent immobilization of AChE by the aptamer results in a 4-fold higher catalytic activity when compared to adsorption directly on to plastic.

Dipeptidyl peptidase-IV inhibitory activity of dimeric dihydrochalcone glycosides from flowers of Helichrysum arenarium.

Science.gov (United States)

Morikawa, Toshio; Ninomiya, Kiyofumi; Akaki, Junji; Kakihara, Namiko; Kuramoto, Hiroyuki; Matsumoto, Yurie; Hayakawa, Takao; Muraoka, Osamu; Wang, Li-Bo; Wu, Li-Jun; Nakamura, Seikou; Yoshikawa, Masayuki; Matsuda, Hisashi

2015-10-01

A methanol extract of everlasting flowers of Helichrysum arenarium L. Moench (Asteraceae) was found to inhibit the increase in blood glucose elevation in sucrose-loaded mice at 500 mg/kg p.o. The methanol extract also inhibited the enzymatic activity against dipeptidyl peptidase-IV (DPP-IV, IC50 = 41.2 μg/ml), but did not show intestinal α-glucosidase inhibitory activities. From the extract, three new dimeric dihydrochalcone glycosides, arenariumosides V-VII (2-4), were isolated, and the stereostructures were elucidated based on their spectroscopic properties and chemical evidence. Of the constituents, several flavonoid constituents, including 2-4, were isolated, and these isolated constituents were investigated for their DPP-IV inhibitory effects. Among them, chalconaringenin 2'-O-β-D-glucopyranoside (16, IC50 = 23.1 μM) and aureusidin 6-O-β-D-glucopyranoside (35, 24.3 μM) showed relatively strong inhibitory activities.

Associations of Physical Activity, Sports Participation and Active Commuting on Mathematic Performance and Inhibitory Control in Adolescents

DEFF Research Database (Denmark)

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 gra...

Is acetylcholinesterase a biomarker of susceptibility in Daphnia magna (Crustacea, Cladocera) after deltamethrin exposure?

Science.gov (United States)

Toumi, Héla; Boumaiza, Moncef; Millet, Maurice; Radetski, Claudemir Marcos; Felten, Vincent; Férard, Jean François

2015-02-01

In the present study, we explored the possibility of using the acetylcholinesterase (AChE) as a biomarker after deltamethrin (pyrethroid insecticide) exposure with three strains of the cladoceran Daphnia magna. Four calculated time-weighted deltamethrin concentrations (20.1, 40.3, 80.6 and 161.3 ng L(-1)) were compared against control acetylcholinesterase activity. Our results showed that after 48 h of deltamethrin exposure, all treatments induced a significant decrease of AChE activities whatever the three considered strains. However, diverse responses were registered in terms of lowest observed effect concentrations (LOEC: 80.6 ng L(-1) for strain 1 and 20.1 ng L(-1) for strains 2 and 3) revealing differences in sensitivity among the three tested strains of D. magna. Our results suggest that after deltamethrin exposure, the AChE activity responses can be also used as a biomarker of susceptibility (i.e., variation of strain specific response). Moreover, our results show that strain 1 is the less sensitive in terms of IC50-48 h of AChE, whereas it became the most sensitive when considering the EC50-48 h estimated in the standard ecotoxicity test. Copyright © 2014 Elsevier Ltd. All rights reserved.

Antioxidant and Acetylcholinesterase Inhibiting Activity of Several Aqueous Tea Infusions in vitro

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Višnja Katalinić

2008-01-01

Full Text Available A study of antioxidant activity and acetylcholineste ase (AChE inhibitory activity of aqueous tea infusions prepared from walnut (Juglans regia L., peppermint (Mentha×piperita L., strawberry (Fragaria×ananassa L., lemon balm (Melissa officinalis L., sage (Salvia officinalis L., and immortelle (Helichrysum arenarium (L. Moench. is presented here. Chemical composition of selected aqueous tea infusions was determined by high-performance liquid chromatography with photodiode-array method (HPLC-PDA, and the following phenolic compounds were identified as dominant: rosmarinic acid, gallic acid (not identified in walnut and sage, caffeic acid (in sage and peppermint, neochlorogenic acid, 3-p-coumaroylquinic acid and quercetin 3-galactoside (in walnut and luteolin 7-O-glucoside (in sage. Antioxidant activity of the selected aqueous tea infusions was measured using low-density lipoprotein (LDL oxidation method, 2,2'-diphenyl-1-picrylhydrazyl (DPPH radical scavenging test, β-carotene bleaching method, and Rancimat method (induction period of lard oxidation. Strawberry and lemon balm aqueous infusions completely inhibited LDL oxidation at the concentration of 0.005 g/L in the reacting system. Very long prolongation of the lag phase was achieved with peppermint and sage aqueous infusions. All tested infusions in the concentration range of 0.05–2.85 g/L showed very pronounced effect of DPPH scavenging activity (90–100 % as well as the inhibition of β-carotene bleaching (89–100 %. In pure lipid medium, used in Rancimat method, sage and immortelle at the concentration of 0.16 % (by mass had the highest ability to inhibit lipid peroxidation process. Screening of the AChE inhibitory activity by Ellman´s method showed that the strongest inhibition was obtained with walnut and strawberry aqueous infusions at the concentration of 1.36 g/L in the reacting system. The presented results suggest that natural antioxidants could be useful and merit further

Inhibitory coupling between inhibitory interneurons in the spinal cord dorsal horn

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Ribeiro-da-Silva Alfredo

2009-05-01

Full Text Available Abstract Local inhibitory interneurons in the dorsal horn play an important role in the control of excitability at the segmental level and thus determine how nociceptive information is relayed to higher structures. Regulation of inhibitory interneuron activity may therefore have critical consequences on pain perception. Indeed, disinhibition of dorsal horn neuronal networks disrupts the balance between excitation and inhibition and is believed to be a key mechanism underlying different forms of pain hypersensitivity and chronic pain states. In this context, studying the source and the synaptic properties of the inhibitory inputs that the inhibitory interneurons receive is important in order to predict the impact of drug action at the network level. To address this, we studied inhibitory synaptic transmission in lamina II inhibitory interneurons identified under visual guidance in spinal slices taken from transgenic mice expressing enhanced green fluorescent protein (EGFP under the control of the GAD promoter. The majority of these cells fired tonically to a long depolarizing current pulse. Monosynaptically evoked inhibitory postsynaptic currents (eIPSCs in these cells were mediated by both GABAA and glycine receptors. Consistent with this, both GABAA and glycine receptor-mediated miniature IPSCs were recorded in all of the cells. These inhibitory inputs originated at least in part from local lamina II interneurons as verified by simultaneous recordings from pairs of EGFP+ cells. These synapses appeared to have low release probability and displayed potentiation and asynchronous release upon repeated activation. In summary, we report on a previously unexamined component of the dorsal horn circuitry that likely constitutes an essential element of the fine tuning of nociception.

Antioxidant, acetylcholinesterase inhibitory activity and cytotoxicity assessment of the crude extracts of Boophane disticha

CSIR Research Space (South Africa)

Adewusi, EA

2012-10-01

Full Text Available . ISSN 2303-9841 79 free-radical intermediates (Liu and Nair, 2010). Since a large amount of evidence demonstrates that oxidative stress is intimately involved in age-related neurodegenerative diseases, there have been a number of studies which have... diseases: A review of their intracellular targets. Eur. J. Pharmacol. 545: 51-64. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M and Rice- Evans C (1999). Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free...

Antioxidant and lipase inhibitory activities and essential oil composition of pomegranate peel extracts.

Science.gov (United States)

Hadrich, Fatma; Cher, Slim; Gargouri, Youssef Talel; Adel, Sayari

2014-01-01

The chemical composition of essential oil, antioxidant and pancreatic lipase inhibitory activities of various solvent extracts obtained from pomegranate peelTunisian cultivar was evaluated. Gas chromatography/mass spectrometry was used to determine the composition of the PP essential oil. Nine-teen components were identified and the main compounds were the camphor (60.32%) and the benzaldehyde (20.98%). The phenolic and flavonoids content varied from 0 to 290.10 mg Gallic acid equivalent and from 5.2 to 20.43 mg catechin equivalent/g dried extract. The antioxidant activity of various solvent extracts from pomegranate peel was also investigated using various in vitro assays as the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical method, β-carotene bleaching and reducing power assays.Methanol and ethanol extracts showed the most potent antioxidant activity in all assays tested followed by water and acetone extracts. The inhibitory effect of the pomegranate peelextracts on porcine pancreatic lipase was evaluated and the results showed that ethanol and methanol extracts markedly reduced lipase activity. Generally, the highestlipase activity inhibitory (100%) was observed at a concentration of 1 mg/ml after 30 min of incubation. LC-MS analysis of ethanol extract showed the presence of four components which are cholorogenic acid, mannogalloylhexoside, gallic acid and ellagic acid. Our findings demonstrate that the ethanol extract from pomegranate peel might be a good candidate for furtherinvestigations of new bioactive substances.

N-[11C]methylpiperidine esters as acetylcholinesterase substrates: an in vivo structure-reactivity study

International Nuclear Information System (INIS)

Kilbourn, Michael R.; Nguyen, Thinh B.; Snyder, Scott E.; Sherman, Phillip

1998-01-01

A series of simple esters incorporating the N-[ 11 C]methylpiperidine structure were examined as in vivo substrates for acetylcholinesterase in mouse brain. 4-N-[ 11 C]Methylpiperidinyl esters, including the acetate, propionate and isobutyrate esters, are good in vivo substrates for mammalian cholinesterases. Introduction of a methyl group at the 4-position of the 4-piperidinol esters, to form the ester of a teritary alcohol, effectively blocks enzymatic action. Methylation of 4- N-[ 11 C]methylpiperidinyl propionate at the 3-position gives a derivative with increased in vivo reactivity toward acetylcholinesterase. Esters of piperidinecarboxylic acids (nipecotic, isonipecotic and pipecolinic acid ethyl esters) are not hydrolyzed by acetylcholinesterase in vivo, nor do they act as in vivo inhibitors of the enzyme. This study has identified simple methods to both increase and decrease the in vivo reactivity of piperidinyl esters toward acetylcholinesterase

The inhibitory effect of Curcuma longa extract on telomerase activity ...

African Journals Online (AJOL)

STORAGESEVER

2010-02-08

Feb 8, 2010 ... curcumin, could have important effect on treatment of lung cancer. Curcumin ... study inhibitory effect of C. longa total extract on telomerase in A549 lung cancer cell line as in vitro model of ..... If A > 2× (OD of negative control), then, telomerase activity ... radiation, chemotherapy, laser therapy, photodynamic.

Self-reported Physical Activity Predicts Pain Inhibitory and Facilitatory Function

Science.gov (United States)

Naugle, Kelly M.; Riley, Joseph L.

2013-01-01

Considerable evidence suggests regular physical activity can reduce chronic pain symptoms. Dysfunction of endogenous facilitatory and inhibitory systems has been implicated in multiple chronic pain conditions. However, few studies have investigated the relationship between levels of physical activity and descending pain modulatory function. Purpose This study’s purpose was to determine whether self-reported levels of physical activity in healthy adults predicted 1) pain sensitivity to heat and cold stimuli, 2) pain facilitatory function as tested by temporal summation of pain (TS), and 3) pain inhibitory function as tested by conditioned pain modulation (CPM) and offset analgesia. Methods Forty-eight healthy adults (age range 18–76) completed the International Physical Activity Questionnaire (IPAQ) and the following pain tests: heat pain thresholds (HPT), heat pain suprathresholds, cold pressor pain (CPP), temporal summation of heat pain, conditioned pain modulation, and offset analgesia. The IPAQ measured levels of walking, moderate, vigorous and total physical activity over the past seven days. Hierarchical linear regressions were conducted to determine the relationship between each pain test and self-reported levels of physical activity, while controlling for age, sex and psychological variables. Results Self-reported total and vigorous physical activity predicted TS and CPM (p’s pain and greater CPM. The IPAQ measures did not predict any of the other pain measures. Conclusion Thus, these results suggest that healthy older and younger adults who self-report greater levels of vigorous and total physical activity exhibit enhanced descending pain modulatory function. Improved descending pain modulation may be a mechanism through which exercise reduces or prevents chronic pain symptoms. PMID:23899890

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

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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.

Monoamine oxidase inhibitory activity in tobacco particulate matter: Are harman and norharman the only physiologically relevant inhibitors?

Science.gov (United States)

Truman, Penelope; Grounds, Peter; Brennan, Katharine A

2017-03-01

Monoamine oxidase inhibition is significant in smokers, but it is still unclear how the inhibition that is seen in the brains and bodies of smokers is brought about. Our aim was to test the contribution of the harman and norharman in tobacco smoke to MAO-A inhibition from tobacco smoke preparations, as part of a re-examination of harman and norharman as the cause of the inhibition of MAO-A inhibition in the brain. Tobacco smoke particulate matter and cigarette smoke particulate matter were prepared and the amounts of harman and norharman measured. The results were compared with the total monoamine oxidase-A inhibitory activity. At a nicotine concentration of 0.6μM (a "physiological" concentration in blood) the total monoamine oxidase-A inhibitory activity measured in these samples was sufficient to inhibit the enzyme by approximately 10%. Of this inhibitory activity, only a small proportion of the total was found to be due to harman and norharman. These results show that harman and norharman provide only a moderate contribution to the total monoamine oxidase-A inhibitory activity of tobacco smoke, perhaps under 10%. This suggests that other inhibitors (either known or unknown) may be more significant contributors to total inhibitory activity than has yet been established, and deserve closer examination. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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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.

Inhibitory effect of vanillin on cellulase activity in hydrolysis of cellulosic biomass.

Science.gov (United States)

Li, Yun; Qi, Benkun; Wan, Yinhua

2014-09-01

Pretreatment of lignocellulosic material produces a wide variety of inhibitory compounds, which strongly inhibit the following enzymatic hydrolysis of cellulosic biomass. Vanillin is a kind of phenolics derived from degradation of lignin. The effect of vanillin on cellulase activity for the hydrolysis of cellulose was investigated in detail. The results clearly showed that vanillin can reversibly and non-competitively inhibit the cellulase activity at appropriate concentrations and the value of IC50 was estimated to be 30 g/L. The inhibition kinetics of cellulase by vanillin was studied using HCH-1 model and inhibition constants were determined. Moreover, investigation of three compounds with similar structure of vanillin on cellulase activity demonstrated that aldehyde group and phenolic hydroxyl groups of vanillin had inhibitory effect on cellulase. These results provide valuable and detailed information for understanding the inhibition of lignin derived phenolics on cellulase. Copyright © 2014 Elsevier Ltd. All rights reserved.

Polypyridylruthenium(II complexes exert anti-schistosome activity and inhibit parasite acetylcholinesterases.

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Madhu K Sundaraneedi

2017-12-01

Full Text Available Schistosomiasis affects over 200 million people and there are concerns whether the current chemotherapeutic control strategy (periodic mass drug administration with praziquantel (PZQ-the only licenced anti-schistosome compound is sustainable, necessitating the development of new drugs.We investigated the anti-schistosome efficacy of polypyridylruthenium(II complexes and showed they were active against all intra-mammalian stages of S. mansoni. Two compounds, Rubb12-tri and Rubb7-tnl, which were among the most potent in their ability to kill schistosomula and adult worms and inhibit egg hatching in vitro, were assessed for their efficacy in a mouse model of schistosomiasis using 5 consecutive daily i.v. doses of 2 mg/kg (Rubb12-tri and 10 mg/kg (Rubb7-tnl. Mice treated with Rubb12-tri showed an average 42% reduction (P = 0.009, over two independent trials, in adult worm burden. Liver egg burdens were not significantly decreased in either drug-treated group but ova from both of these groups showed significant decreases in hatching ability (Rubb12-tri-68%, Rubb7-tnl-56% and were significantly morphologically altered (Rubb12-tri-62% abnormal, Rubb7-tnl-35% abnormal. We hypothesize that the drugs exerted their activity, at least partially, through inhibition of both neuronal and tegumental acetylcholinesterases (AChEs, as worms treated in vitro showed significant decreases in activity of these enzymes. Further, treated parasites exhibited a significantly decreased ability to uptake glucose, significantly depleted glycogen stores and withered tubercules (a site of glycogen storage, implying drug-mediated interference in this nutrient acquisition pathway.Our data provide compelling evidence that ruthenium complexes are effective against all intra-mammalian stages of schistosomes, including schistosomula (refractory to PZQ and eggs (agents of disease transmissibility. Further, the results of this study suggest that schistosome AChE is a target of

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

Science.gov (United States)

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

2017-11-01

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

MAO-A inhibitory activity of quercetin from Calluna vulgaris (L.) Hull

DEFF Research Database (Denmark)

Saaby, Lasse; Rasmussen, Hasse Bonde; Jäger, Anna Katharina

2009-01-01

AIM OF THE STUDY: This study investigated MAO-A inhibitory activity of methanol extract of Calluna vulgaris (L.) Hull., which traditionally has been used as a nerve calming remedy. MATERIALS AND METHODS: A methanolic extract of Calluna vulgaris was partitioned against heptane, ethyl acetate...

Inhibitory activity and conformational transition of alpha 1-proteinase inhibitor variants

NARCIS (Netherlands)

Schulze, A.J.; Huber, R.; Degryse, E.; Speck, D.; Bischoff, Rainer

1991-01-01

Several variants of alpha 1-proteinase inhibitor (alpha 1-PI) were investigated by spectroscopic methods and characterized according to their inhibitory activity. Replacement of Thr345 (P14) with Arg in alpha 1-PI containing an Arg residue in position 358 (yielding [Thr345----Arg,

Evaluation of Apoptotic and Growth Inhibitory Activity of Phloretin in ...

African Journals Online (AJOL)

Results: The results show that the inhibitory activity of phloretin in BGC823 gastric cancer cells was mediated by induction of apoptosis ... anti-proliferative effects of phloretin was dose-dependent and inhibited the growth of BGC823 gastric cancer cells by 73 % at 30 μM; .... weeks at 37 °C in 5 % CO2 in humidified incubator.

Valuing the Endangered Species Antirrhinum lopesianum: Neuroprotective Activities and Strategies for in vitro Plant Propagation.

Science.gov (United States)

Gomes, Andreia; Fortalezas, Sofia; Pimpão, Rui; Figueira, Inês; Maroco, João; Aguiar, Carlos; Ferreira, Ricardo B; Miguel, Célia; Santos, Cláudia N

2013-10-28

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 territory, within 20 years. Here, we describe for the first time the chemical characterization of extracts of the species concerning total phenol content, flavonoid content and antioxidant properties. The profile of high performance liquid chromatography with diode array detector (HPLC-DAD) of the polyphenol-enriched fraction of plant extracts was also performed, showing the great potential of the species as a source of bioactive phytochemical compounds. A. lopesianum's potential for neuroprotection was revealed by a significant acetylcholinesterase inhibitory activity and also by a neuroprotective effect on a human cell model of neurodegeneration. Moreover, this is the first report describing a successful procedure for the in vitro propagation of this endangered species. The comparison of phenolic content and the HPLC-DAD profile of wild and in vitro propagated plants revealed that in vitro plants maintain the ability to produce secondary metabolites, but the profiles are differentially affected by the growth regulators. The results presented here greatly contribute to the value for this species regarding its potential as a source of phytochemicals with prospective neuroprotective health benefits.

Valuing the Endangered Species Antirrhinum lopesianum: Neuroprotective Activities and Strategies for in vitro Plant Propagation

Science.gov (United States)

Gomes, Andreia; Fortalezas, Sofia; Pimpão, Rui; Figueira, Inês; Maroco, João; Aguiar, Carlos; Ferreira, Ricardo B.; Miguel, Célia; Santos, Cláudia N.

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 territory, within 20 years. Here, we describe for the first time the chemical characterization of extracts of the species concerning total phenol content, flavonoid content and antioxidant properties. The profile of high performance liquid chromatography with diode array detector (HPLC-DAD) of the polyphenol-enriched fraction of plant extracts was also performed, showing the great potential of the species as a source of bioactive phytochemical compounds. A. lopesianum’s potential for neuroprotection was revealed by a significant acetylcholinesterase inhibitory activity and also by a neuroprotective effect on a human cell model of neurodegeneration. Moreover, this is the first report describing a successful procedure for the in vitro propagation of this endangered species. The comparison of phenolic content and the HPLC-DAD profile of wild and in vitro propagated plants revealed that in vitro plants maintain the ability to produce secondary metabolites, but the profiles are differentially affected by the growth regulators. The results presented here greatly contribute to the value for this species regarding its potential as a source of phytochemicals with prospective neuroprotective health benefits. PMID:26784465

Valuing the Endangered Species Antirrhinum lopesianum: Neuroprotective Activities and Strategies for in vitro Plant Propagation

Directory of Open Access Journals (Sweden)

Andreia Gomes

2013-10-01

Full Text Available 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 territory, within 20 years. Here, we describe for the first time the chemical characterization of extracts of the species concerning total phenol content, flavonoid content and antioxidant properties. The profile of high performance liquid chromatography with diode array detector (HPLC-DAD of the polyphenol-enriched fraction of plant extracts was also performed, showing the great potential of the species as a source of bioactive phytochemical compounds. A. lopesianum’s potential for neuroprotection was revealed by a significant acetylcholinesterase inhibitory activity and also by a neuroprotective effect on a human cell model of neurodegeneration. Moreover, this is the first report describing a successful procedure for the in vitro propagation of this endangered species. The comparison of phenolic content and the HPLC-DAD profile of wild and in vitro propagated plants revealed that in vitro plants maintain the ability to produce secondary metabolites, but the profiles are differentially affected by the growth regulators. The results presented here greatly contribute to the value for this species regarding its potential as a source of phytochemicals with prospective neuroprotective health benefits.

Comparative study on the antioxidant capacity and cholinesterase inhibitory activity of Citrus aurantifolia Swingle, C. aurantium L., and C. bergamia Risso and Poit. peel essential oils.

Science.gov (United States)

Tundis, Rosa; Loizzo, Monica Rosa; Bonesi, Marco; Menichini, Federica; Mastellone, Vincenzo; Colica, Carmela; Menichini, Francesco

2012-01-01

The interest in medicinal plant research and in the aroma-therapeutic effects of essential oils in humans has increased in recent years, especially for the treatment of pathologies of relevant social impact such as Alzheimer's disease. The present study was taken up to evaluate the antioxidant capacity and the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity of the peel essential oils from three Citrus species, C. aurantifolia Swingle, C. aurantium L., and C. bergamia Risso & Poit. Essential oils were analyzed by GC and GC-MS and they contain mainly limonene, α-pinene, β-pinene, γ-terpinene, and linalyl acetate. C. aurantifolia oil showed the highest radical scavenging activity on ABTS assay (IC₅₀ value of 19.6 μg/mL), while C. bergamia exhibited a good antioxidant activity evaluated by the β-carotene bleaching test (IC₅₀ = 42.6 μg/mL after 60 min of incubation). C. aurantifolia inhibited more selectively AChE. Obtained data suggest a potential use of Citrus oils as a valuable new flavor with functional properties for food or nutraceutical products with particular relevance to supplements for the elderly. The demonstrated antioxidant activity and procholinesterase properties of Citrus essential oils suggested their use as a new potential source of natural antioxidant to added as extra-nutrient for using in food industries as a valuable new flavor with functional properties for food or nutraceutical products with particular relevance to supplements for the elderly. © 2011 Institute of Food Technologists®

Relationships between the structure of wheat gluten and ACE inhibitory activity of hydrolysate: stepwise multiple linear regression analysis.

Science.gov (United States)

Zhang, Yanyan; Ma, Haile; Wang, Bei; Qu, Wenjuan; Wali, Asif; Zhou, Cunshan

2016-08-01

Ultrasound pretreatment of wheat gluten (WG) before enzymolysis can improve the angiotensin converting enzyme (ACE) inhibitory activity of the hydrolysates by alerting the structure of substrate proteins. Establishment of a relationship between the structure of WG and ACE inhibitory activity of the hydrolysates to judge the end point of the ultrasonic pretreatment is vital. The results of stepwise multiple linear regression (MLR) showed that the contents of free sulfhydryl, α-helix, disulfide bond, surface hydrophobicity and random coil were significantly correlated to ACE Inhibitory activity of the hydrolysate, with the standard partial regression coefficients were 3.729, -0.676, -0.252, 0.022 and 0.156, respectively. The R(2) of this model was 0.970. External validation showed that the stepwise MLR model could well predict the ACE inhibitory activity of hydrolysate based on the content of free sulfhydryl, α-helix, disulfide bond, surface hydrophobicity and random coil of WG before hydrolysis. A stepwise multiple linear regression model describing the quantitative relationships between the structure of WG and the ACE Inhibitory activity of the hydrolysates was established. This model can be used to predict the endpoint of the ultrasonic pretreatment. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

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

Science.gov (United States)

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

2016-02-02

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. © 2016 Authors.

Chemical Composition, Antioxidant and Anticholinesterase Activities of the Essential oil of Origanum rotundifolium Boiss. from Turkey

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Hilal Özbek

2017-09-01

Full Text Available The essential oil was obtained by hydrodistillation from the aerial parts of Origanum rotundifolium Boiss. Its chemical content and composition were analyzed by using a gas chromatography (GC-FID and gas chromatography-mass spectrometry (GC-MS. Total phenolic content of the essential oil was determined as 132.39 µg gallic acid equivalent by Folin–Ciocalteu’s method and the major component was identified as carvacrol (56.8 % along with p-cymene (13.1 %, (Z- b -ocimene (5.4 %, b -caryophyllene (3.9 %, borneol (3.4 % and thymol (3.2 %. After chemical characterization, the essential oil was evaluated for its antioxidant activity by DPPH free radical, superoxide anion radical and hydrogen peroxide scavenging activities as well as ferrous ion-chelating power test, ABTS radical cation decolorization assay and ferric thiocyanate methods. Besides antioxidant activity, acetylcholinesterase and butyrylcholinesterase inhibitory activities of the essential oil were also evaluated by Ellman’s method. It demonstrated inhibitory activities on AChE and BuChE, key enzymes in the pathogenesis of Alzheimer’s disease (AD, in addition to significant antioxidant activity.

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

Science.gov (United States)

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

2016-05-04

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.

Antitubercular activity and inhibitory effect on Epstein-Barr virus activation of sterols and polyisoprenepolyols from an edible mushroom, Hypsizigus marmoreus.

Science.gov (United States)

Akihisa, Toshihiro; Franzblau, Scott Gary; Tokuda, Harukuni; Tagata, Masaaki; Ukiya, Motohiko; Matsuzawa, Tsunetomo; Metori, Koichi; Kimura, Yumiko; Suzuki, Takashi; Yasukawa, Ken

2005-06-01

Seven sterols (1-7) and eight polyisoprenepolyols (8-15), isolated from the non-saponifiable lipid fraction of the dichloromethane extract of an edible mushroom, Hypsizigus marmoreus (Buna-shimeji), were tested for their antitubercular activity against Mycobacterium tuberculosis strain H37Rv using the Microplate Alamar Blue Assay (MABA). Six sterols (2-7) and two polyisoprenepolyols (8, 12) showed a minimum inhibitory concentration (MIC) in the range of 1-51 microg/ml, while the others (1, 9-11, 13-15) were inactive (MIC>128 microg/ml). The seven sterols (1-7) and three polyisoprenepolyols (8, 10, 12) were further evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Sterols 6 and 7 showed potent inhibitory effects while preserving the high viability of Raji cells.

Lanostane triterpenes from the mushroom Ganoderma resinaceum and their inhibitory activities against α-glucosidase.

Science.gov (United States)

Chen, Xian-Qiang; Zhao, Jing; Chen, Ling-Xiao; Wang, Shen-Fei; Wang, Ying; Li, Shao-Ping

2018-05-01

Eighteen previously undescribed lanostane triterpenes and thirty known analogues were obtained from the fruiting bodies of Ganoderma resinaceum. Resinacein C was isolated from a natural source for the first time. The structures of all the above compounds were elucidated by extensive spectroscopic analysis and comparisons of their spectroscopic data with those reported in the literature. Furthermore, in an in vitro assay, Resinacein C, ganoderic acid Y, lucialdehyde C, 7-oxo-ganoderic acid Z 3 , 7-oxo-ganoderic acid Z, and lucidadiol showed strong inhibitory effects against α-glucosidase compared with the positive control drug acarbose. The structure-activity relationships of ganoderma triterpenes on α-glucosidase inhibition showed that the C-24/C-25 double bond is necessary for α-glucosidase inhibitory activity. Moreover, the carboxylic acid group at C-26 and the hydroxy group at C-15 play important roles in enhancing inhibitory effects of these triterpenes. Copyright © 2018. Published by Elsevier Ltd.

High-performance liquid chromatography-mass spectrometry-based acetylcholinesterase assay for the screening of inhibitors in natural extracts

NARCIS (Netherlands)

de Jong, C.F.; Derks, R.J.E.; Bruyneel, B.; Niessen, W.M.A.; Irth, H.

2006-01-01

The present paper describes a High-performance liquid chromatography-mass spectrometry (LC-MS) methodology for the screening of acetylcholinesterase (AChE) inhibitors in natural extracts. AChE activity of sample components is monitored by a post-column biochemical assay that is based on the

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

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Jucilene Silva Araújo

2017-04-01

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

Synthesis of chiral pyrazolo[4,3-e][1,2,4]triazine sulfonamides with tyrosinase and urease inhibitory activity.

Science.gov (United States)

Mojzych, Mariusz; Tarasiuk, Paweł; Kotwica-Mojzych, Katarzyna; Rafiq, Muhammad; Seo, Sung-Yum; Nicewicz, Michał; Fornal, Emilia

2017-12-01

A new series of sulfonamide derivatives of pyrazolo[4,3-e][1,2,4]triazine with chiral amino group has been synthesized and characterized. The compounds were tested for their tyrosinase and urease inhibitory activity. Evaluation of prepared derivatives demonstrated that compounds (8b) and (8j) are most potent mushroom tyrosinase inhibitors whereas all of the obtained compounds showed higher urease inhibitory activity than the standard thiourea. The compounds (8a), (8f) and (8i) exhibited excellent enzyme inhibitory activity with IC 50 0.037, 0.044 and 0.042 μM, respectively, while IC 50 of thiourea is 20.9 μM.

Volatile Profiling of Aromatic Traditional Medicinal Plant, Polygonum minus in Different Tissues and Its Biological Activities

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Rafidah Ahmad

2014-11-01

Full Text Available The aim of this research was to identify the volatile metabolites produced in different organs (leaves, stem and roots of Polygonum minus, an important essential oil producing crop in Malaysia. Two methods of extraction have been applied: Solid Phase Microextraction (SPME and hydrodistillation coupled with Gas Chromatography-Mass Spectrometry (GC-MS. Approximately, 77 metabolites have been identified and aliphatic compounds contribute significantly towards the aroma and flavour of this plant. Two main aliphatic compounds: decanal and dodecanal were found to be the major contributor. Terpenoid metabolites were identified abundantly in leaves but not in the stem and root of this plant. Further studies on antioxidant, total phenolic content, anticholinesterase and antimicrobial activities were determined in the essential oil and five different extracts. The plant showed the highest DPPH radical scavenging activity in polar (ethanol extract for all the tissues tested. For anti-acetylcholinesterase activity, leaf in aqueous extract and methanol extract showed the best acetylcholinesterase inhibitory activities. However, in microbial activity, the non-polar extracts (n-hexane showed high antimicrobial activity against Methicillin-resistant Staphylococcus aureus (MRSA compared to polar extracts. This study could provide the first step in the phytochemical profiles of volatile compounds and explore the additional value of pharmacology properties of this essential oil producing crop Polygonum minus.

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

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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

Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and Parkinson’s disease dementia

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Kandiah N

2017-04-01

Full Text Available Nagaendran Kandiah,1,2 Ming-Chyi Pai,3,4 Vorapun Senanarong,5 Irene Looi,6,7 Encarnita Ampil,8 Kyung Won Park,9 Ananda Krishna Karanam,10 Stephen Christopher11 1Department of Neurology, National Neuroscience Institute, Tan Tock Seng Hospital, 2Duke-NUS, Graduate Medical School, Singapore; 3Division of Behavioral Neurology, Department of Neurology, 4Alzheimer’s Disease Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan City, Taiwan; 5Division of Neurology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand; 6Clinical Research Centre, 7Department of Medicine, Hospital Seberang Jaya, Penang, Malaysia; 8Department of Neurology and Psychiatry, Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines; 9Department of Neurology and Cognitive Disorders and Dementia Center, Institute of Convergence Bio-Health, Dong-A University College of Medicine, Busan, Republic of Korea; 10Novartis Healthcare Private Limited, Hyderabad, India; 11Novartis (Singapore Pte. Ltd., Singapore Abstract: Several studies have demonstrated clinical benefits of sustained cholinesterase inhibition with rivastigmine in Alzheimer’s disease (AD and Parkinson’s disease dementia (PDD. Unlike donepezil and galantamine that selectively inhibit acetylcholinesterase (AChE; EC 3.1.1.7, rivastigmine is a unique cholinesterase inhibitor with both AChE and butyrylcholinesterase (BuChE; EC 3.1.1.8 inhibitory activity. Rivastigmine is also available as transdermal patch that has been approved by the US Food and Drug Administration for the treatment of mild, moderate, and severe AD as well as mild-to-moderate PDD. In this review, we explore the role of BuChE inhibition in addition to AChE inhibition with rivastigmine in the outcomes of cognition, global function, behavioral symptoms, and activities of daily living. Additionally, we review the evidence supporting the use of dual

Alkaloids from the leaves of Uncaria rhynchophylla and their inhibitory activity on NO production in lipopolysaccharide-activated microglia.

Science.gov (United States)

Yuan, Dan; Ma, Bin; Wu, Chunfu; Yang, Jingyu; Zhang, Lijia; Liu, Suiku; Wu, Lijun; Kano, Yoshihiro

2008-07-01

Two new isomeric alkaloids, 18,19-dehydrocorynoxinic acid B (1) and 18,19-dehydrocorynoxinic acid (2), were isolated from the CHCl3 extract of the leaves of Uncaria rhynchophylla, together with four known rhynchophylline-type alkaloids, corynoxeine (3), isocorynoxeine (4), rhynchophylline (5), and isorhynchophylline (6), and an indole alkaloid glucoside, vincoside lactam (7). The structures of compounds 1 and 2 were elucidated by spectroscopic methods including UV, IR, HREIMS, 1D and 2D NMR, and CD experiments. The activity assay showed that compounds 3-6, with a C-16 carboxylic ester group, and 7 exhibited inhibitory activity on lipopolysaccharide (LPS)-induced NO release in primary cultured rat cortical microglia (IC 50: 13.7-19.0 microM). However, only weak inhibitory activity was observed for compounds 1 and 2, with a C-16 carboxylic acid group (IC 50: >100 microM).

DNA damage, acetylcholinesterase activity and lysosomal stability in native and transplanted mussels (Mytilus edulis) in areas close to coastal chemical dumping sites in Denmark

DEFF Research Database (Denmark)

Rank, Jette; Lehtonen, Kari K.; Strand, Jakob

2007-01-01

Biomarkers of genotoxicity (DNA damage, measured as tail moment in the Comet assay), neurotoxicity (acetylcholinesterase inhibition, AChE) and general stress (lysosomal membrane stability, LMS) were studied in native and transplanted blue mussels (Mytilus edulis) in coastal areas of western Denmark...... of chemical pollution complex, as seen especially in the variability in results on DNA damage, and also in regard to AChE activity. These investigations further stress the importance of understanding the effects of natural factors (salinity, temperature, water levels, rain and storm events) in correct...

Antioxidant, ACE-Inhibitory and antibacterial activities of Kluyveromyces marxianus protein hydrolysates and their peptide fractions

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Mahta Mirzaeia

2016-07-01

Full Text Available Background: There has been evidence that proteins are potentially excellent source of antioxidants, antihypertensive and antimicrobial peptides, and that enzymatic hydrolysis is an effective method to release these peptides from protein molecules. The functional properties of protein hydrolysates depends on the protein substrate, the specificity of the enzymes, the conditions used during proteolysis, degree of hydrolysis, and the nature of peptides released including molecular weight, amino acid composition, and hydrophobicity. Context and purpose of this study: The biomass of Kluyveromyces marxianus was considered as a source of ACE inhibitory, antioxidant and antimicrobial peptides. Results: Autolysis and enzymatic hydrolysis were completed respectively, after 96 h and 5 h. Overall, trypsin (18.52% DH and chymotrypsin (21.59% DH treatments were successful in releasing antioxidant and ACE inhibitory peptides. Autolysate sample (39.51% DH demonstrated poor antioxidant and ACE inhibitory activity compared to trypsin and chymotrypsin hydrolysates. The chymotrypsin 3-5 kDa (301.6±22.81 μM TE/mg protein and trypsin < 3 kDa (280.16±39.16 μM TE/mg protein permeate peptide fractions showed the highest DPPH radical scavenging activity. The trypsin <3 kDa permeate peptide fraction showed the highest ABTS radical scavenging (1691.1±48.68 μM TE/mg protein and ACE inhibitory (IC50=0.03±0.001 mg/mL activities. The fraction (MW=5-10 kD obtained after autolysis treatment showed antibacterial activity against St. aureus and Lis. monocytogenes in well diffusion screening. The minimum inhibitory concentration (MIC value was 13.3 mg/mLagainst St. aureus and Lis. monocytogenes calculated by turbidimetric assay and it showed bactericidal activity against St. aureus at 21.3 mg/mL protein concentration. Conclusions: Altogether, the results of this study reveal that K. marxianus proteins contain specific peptides in their sequences which can be released by

Chemical Composition and Enzymes Inhibitory, Brine Shrimp Larvae Toxicity, Antimicrobial and Antioxidant Activities of Caloplaca biatorina

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Tahereh Valadbeigi

2016-10-01

Full Text Available Background This study evaluated the brine shrimp larvae toxicity and enzymes inhibitory especially anti-diabetic potential of Caloplaca biatorina via in vitro inhibition of α-amylase and α-glucosidase using the methanol extracts. Also aldehyde oxidase and xanthine oxidase enzymes inhibitory, cytotoxicity, and antioxidant activities of the species were determined. Methods In this experimental study, different concentrations of the extracts (0.2, 5.0, 1 and 1.5 mg/mL were incubated with enzyme substrate solution and the percentage of enzyme inhibitory activity and IC50 was calculated. Folin- Ciocalteu reagent and aluminium chloride colorimetric methods were used to estimate total phenolic and flavonoid content of extracts. The toxicity of the extract was assessed using the brine shrimp lethality bioassay. The minimal inhibitory concentration (MIC and minimum bactericidal concentration (MBC were determined. High-performance liquid chromatography and Thin-layer chromatography analysis were evaluated. The data were analyzed by SPSS V.21 software. Results Parietin, Emodin, 1,8-Dihydroxy-3-(hydroxymethyl-6- methoxy-9.10-anthracenedione and Rhein were identified. The extract showed strong α-glucosidase, aldehyde oxidase and xanthine oxidase inhibitory activities with IC50 value of 17.12, 40.09 and 11.02 µg/mL respectively. Also methanol extract displayed the strongest DPPH radical scavenging and brine shrimp toxicity (IC50 = 91.11 properties. Conclusions The result obtained suggests that the C. biatorina extract can be classified as non-toxic. Also, it revealed the antioxidant and antidiabetic potential of the lichen.

Bistability Analysis of Excitatory-Inhibitory Neural Networks in Limited-Sustained-Activity Regime

International Nuclear Information System (INIS)

Ni Yun; Wu Liang; Wu Dan; Zhu Shiqun

2011-01-01

Bistable behavior of neuronal complex networks is investigated in the limited-sustained-activity regime when the network is composed of excitatory and inhibitory neurons. The standard stability analysis is performed on the two metastable states separately. Both theoretical analysis and numerical simulations show consistently that the difference between time scales of excitatory and inhibitory populations can influence the dynamical behaviors of the neuronal networks dramatically, leading to the transition from bistable behaviors with memory effects to the collapse of bistable behaviors. These results may suggest one possible neuronal information processing by only tuning time scales. (interdisciplinary physics and related areas of science and technology)

In vitro inhibitory activities of the extract of Hibiscus sabdariffa L ...

African Journals Online (AJOL)

In vitro inhibitory activities of the extract of Hibiscus sabdariffa L. (family malvaceae) on selected cytochrome p450 isoforms. SS Johnson, FT Oyelola, T Ari, H Juho. Abstract. Literature is scanty on the interaction potential of Hibiscus sabdariffa L., plant extract with other drugs and the affected targets. This study was ...

In vitro toxicity, antiplatelet and acetylcholinesterase inhibition of Buddleja thyrsoides Lam. leaves.

Science.gov (United States)

Mahlke, Janaína Dorneles; Boligon, Aline Augusti; Machado, Michel Mansur; Athayde, Margareth Linde

2012-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder resulting in impaired memory and behaviour of remarkable socio-economic impact. A decrease in cholinergic activity is a key event in the biochemical of AD. Buddleja thyrsoides is a plant widely distributed in Southern parts of South America. In Brazilian traditional medicine, the infusion of its leaves and flowers is used for the treatment of bronchitis and cough. Crude ethanolic (70%) extract and fractions (dichloromethane, ethyl acetate and n-butanolic) were investigated regarding their toxicities in vitro and antiplatelet action. The enzyme acetylcholinesterase inhibition was evaluated to study the crude extract. The crude extract and fractions were evaluated by means of Brine Shrimp Lethality test and they showed low activities with LC(50) values 1698, 2818, 2187 and 3672 µg mL(-1) for dichloromethane, ethyl acetate, n-butanolic fractions and crude extract, respectively. Buddleja thyrsoides presented great antiplatelet action. The IC(50) values obtained for crude extract and dichloromethane, ethyl acetate and n-butanolic fractions were 361.29, 354.23, 368.75 and 344.30, respectively, while the IC(50) for the standard AAS was 257.01 µg mL(-1). The crude extract showed an inhibition of 22.8% of the acetylcholinesterase enzyme in 24 h.

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

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Irie, Toshiaki [National Inst. of Radiological Sciences, Chiba (Japan)

1999-07-01

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 [{sup 11}C]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

Synthesis of 1-[11c]methylpiperidin-4-yl propionate ([11c]pmp) for in vivo measurements of acetylcholinesterase activity

International Nuclear Information System (INIS)

Snyder, Scott E.; Tluczek, Louis; Jewett, Douglas M.; Nguyen, Thinh B.; Kuhl, David E.; Kilbourn, Michael R.

1998-01-01

Synthesis of 1-[ 11 C]methylpiperidin-4-yl propionate ([ 11 C]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 [ 11 C]methyl trifluoromethanesulfonate at room temperature in N,N-dimethylformamide, followed by high performance liquid chromatography (HPLC) purification, provided [ 11 C]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. [ 11 C]PMP can thus be reliably prepared for routine clinical studies of acetylcholinesterase in human brain using positron emission tomography

Inhibitory effect of rhubarb on intestinal α-glucosidase activity in type ...

African Journals Online (AJOL)

Purpose: To investigate the inhibitory effect of rhubarb on α-glucosidase activity in the small intestine of rats with type 1 diabetes. Methods: Type 1 diabetic rat model was established by intraperitoneally injecting 30 male SD rats with 1 % streptozocin (STZ). Rats with fasting blood glucose > 11 mmol/L (24) were used for the ...

Chemical composition of the essential oil and hexane extract of Salvia chionantha and their antioxidant and anticholinesterase activities.

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Tel, Gülsen; Oztürk, Mehmet; Duru, Mehmet Emin; Harmandar, Mansur; Topçu, Gülaçti

2010-11-01

The essential oil and methyl ester of hexane extract of Salvia chionantha Boiss. were analysed by GC and GC-MS. Totally, 54 components were detected in the essential oil and all of them were fully determined. Germacrene D (25.03%), β-caryophyllene (8.71%), spathulenol (5.86%) and α-humulene (4.82%) were identified as the major compounds. In the methylated hexane extract, 3-hydroxy hexadecanoic acid (39.39%), 3-hydroxy tetradecanoic acid (12.66%) and palmitic acid (12.02%) were the major fatty acids elucidated. The antioxidant activity of the essential oil and the hexane extract was determined by using four complementary test systems; namely, β-carotene-linoleic acid, DPPH() scavenging, ABTS(+)* scavenging, and CUPRAC assays. In β-carotene-linoleic acid assay, the extract showed 81.2±0.1% lipid peroxidation inhibition at 0.8 mg/mL concentration, while in ABTS(+)* assay the essential oil exhibited 77.4±0.5% inhibition at same concentration. Since, acetylcholinesterase and butyrylcholinesterase enzymes are taking place in pathogenesis of Alzheimer's disease, in vitro anticholinesterase activity of the essential oil and the extract was also studied spectrophotometrically. At 0.5mg/mL concentration, the essential oil showed moderate acetylcholinesterase (56.7±1.9%) and butyrylcholinesterase (41.7±2.9%) inhibitory activity, while the extract was only exhibited activity (63.1±0.8%) against butyrylcholinesterase enzyme. Hence, the essential oil may be useful as a moderate anticholinesterase agent, particularly against acetylcholinesterase. Copyright © 2010 Elsevier Ltd. All rights reserved.

A Subtype of Inhibitory Interneuron with Intrinsic Persistent Activity in Human and Monkey Neocortex

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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.

The interactions of azure B, a metabolite of methylene blue, with acetylcholinesterase and butyrylcholinesterase

International Nuclear Information System (INIS)

Petzer, Anél; Harvey, Brian H.; Petzer, Jacobus P.

2014-01-01

Methylene blue (MB) is reported to possess diverse pharmacological actions and is attracting increasing attention for the treatment of neurodegenerative disorders such as Alzheimer's disease. Among the pharmacological actions of MB, is the significant inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These activities may, at least in part, underlie MB's beneficial effects in Alzheimer's disease. MB is metabolized to yield N-demethylated products of which azure B, the monodemethyl metabolite, is the predominant species. Azure B has been shown to be pharmacologically active and also possesses a variety of biological actions. Azure B therefore may contribute to the pharmacological profile of MB. Based on these considerations, the present study investigates the possibility that azure B may, similar to MB, act as an inhibitor of human AChE and BuChE. The results document that azure B inhibits AChE and BuChE with IC 50 values of 0.486 μM and 1.99 μM, respectively. The results further show that azure B inhibits AChE and BuChE reversibly, and that the modes of inhibition are most likely competitive. Although the AChE and BuChE inhibitory activities of azure B are twofold and fivefold, respectively, less potent than those recorded for MB [IC 50 (AChE) = 0.214 μM; IC 50 (BuChE) = 0.389 μM] under identical conditions, azure B may be a contributor to MB's in vivo activation of the cholinergic system and beneficial effects in Alzheimer's disease. - Highlights: • Methylene blue (MB) is a known inhibitor of AChE and BuChE. • Azure B, the major metabolite of MB, also is an inhibitor of AChE and BuChE. • Azure B may be a contributor to MB's in vivo activation of the cholinergic system. • Azure B may contribute to MB's potential in Alzheimer's disease therapy

Two new compounds from the fruiting bodies of Ganoderma philippii.

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Yang, Shuang; Ma, Qing-Yun; Kong, Fan-Dong; Xie, Qing-Yi; Huang, Sheng-Zhuo; Zhou, Li-Man; Dai, Hao-Fu; Yu, Zhi-Fang; Zhao, You-Xing

2018-03-01

Two new compounds, philippin (1) and 3β,9α,14α-trihydroxy-(22E,24R)-ergost-22-en-7-one (2), were isolated from the fruiting bodies of Ganoderma philippii. Their structures were elucidated on the basis of the spectroscopic technologies, including 1D and 2D NMR as well as MS. The bioassay of inhibitory activity against acetylcholinesterase (AChE) showed compound 1 exhibited weak inhibitory activity against AChE.

Proline-induced changes in acetylcholinesterase activity and gene expression in zebrafish brain: reversal by antipsychotic drugs.

Science.gov (United States)

Savio, L E B; Vuaden, F C; Kist, L W; Pereira, T C; Rosemberg, D B; Bogo, M R; Bonan, C D; Wyse, A T S

2013-10-10

Hyperprolinemia is an inherited disorder of proline metabolism and hyperprolinemic patients can present neurological manifestations, such as seizures, cognitive dysfunctions, and schizoaffective disorders. However, the mechanisms related to these symptoms are still unclear. In the present study, we evaluated the in vivo and in vitro effects of proline on acetylcholinesterase (AChE) activity and gene expression in the zebrafish brain. For the in vivo studies, animals were exposed at two proline concentrations (1.5 and 3.0mM) during 1h or 7 days (short- or long-term treatments, respectively). For the in vitro assays, different proline concentrations (ranging from 3.0 to 1000 μM) were tested. Long-term proline exposures significantly increased AChE activity for both treated groups when compared to the control (34% and 39%). Moreover, the proline-induced increase on AChE activity was completely reverted by acute administration of antipsychotic drugs (haloperidol and sulpiride), as well as the changes induced in ache expression. When assessed in vitro, proline did not promote significant changes in AChE activity. Altogether, these data indicate that the enzyme responsible for the control of acetylcholine levels might be altered after proline exposure in the adult zebrafish. These findings contribute for better understanding of the pathophysiology of hyperprolinemia and might reinforce the use of the zebrafish as a complementary vertebrate model for studying inborn errors of amino acid metabolism. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

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

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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)

Molecular Descriptors Family on Vertex Cutting: Relationships between Acelazolamide Structures and their Inhibitory Activity

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Sorana D. BOLBOACĂ

2009-12-01

Full Text Available Aim: To investigate the relationship between the structural information of acetazolamides and their inhibitory activity on carbonic anhydrase II. Material and Method: A sample of previously reported acetazolamides was studied. A pool of descriptors was calculated based on matrix representation and vertex cut in order to be included in the multiple linear regression analysis. The best performing model in terms of goodness-of-fit was analysed in order to assess its validity and reliability. The model was compared with previously reported models using a series of information and prediction criteria besides the Steiger’s Z test. Results: A model with a 99.77% determination coefficient proved to be the best performing model. The obtained model proved to have a less than 5% average of the absolute difference between the observed and the estimated inhibitory activity. The information and prediction criteria showed that the obtained model was better than the previously reported models. This conclusion is also sustained by the results of Steiger’s Z test (7.78; p = 3.66·10-15. Conclusion: The inhibitory activity on carbonic anhydrase II of acetazolamides proved to be of geometric and topologic nature and depended on the compounds’ melting point, relative atomic mass and atomic electronegativity.

Inhibitory Effect and Mechanism of Arctium lappa Extract on NLRP3 Inflammasome Activation.

Science.gov (United States)

Kim, Young-Kyu; Koppula, Sushruta; Shim, Do-Wan; In, Eun-Jung; Kwak, Su-Bin; Kim, Myong-Ki; Yu, Sang-Hyeun; Lee, Kwang-Ho; Kang, Tae-Bong

2018-01-01

Arctium lappa (A. lappa) , Compositae, is considered a potential source of nutrition and is used as a traditional medicine in East Asian countries for centuries. Although several studies have shown its biological activities as an anti-inflammatory agent, there have been no reports on A. lappa with regard to regulatory role in inflammasome activation. The purpose of this study was to investigate the inhibitory effects of A. lappa extract (ALE) on NLRP3 inflammasome activation and explore the underlying mechanisms. We found that ALE inhibited IL-1 β secretion from NLRP3 inflammasome activated bone marrow derived macrophages but not that secreted by NLRC4 and AIM2 inflammasomes activation. Mechanistic studies revealed that ALE suppressed the ATPase activity of purified NLRP3 and reduced mitochondrial reactive oxygen species (mROS) generated during NLRP3 activation. Therefore, the inhibitory effect of ALE on NLRP3 inflammasome might be attributed to its ability to inhibit the NLRP3 ATPase function and attenuated the mROS during inflammasome activation. In addition, ALE significantly reduced the LPS-induced increase of plasma IL-1 β in mouse peritonitis model. These results provide evidence of novel anti-inflammatory mechanisms of A. lappa , which might be used for therapeutic applications in the treatment of NLRP3 inflammasome-associated inflammatory disorders.

Anti-Alzheimer's disease activity of compounds from the root bark of Morus alba L.

Science.gov (United States)

Kuk, Eun Bi; Jo, A Ra; Oh, Seo In; Sohn, Hee Sook; Seong, Su Hui; Roy, Anupom; Choi, Jae Sue; Jung, Hyun Ah

2017-03-01

The inhibition of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) plays important roles in prevention and treatment of Alzheimer's disease (AD). Among the individual parts of Morus alba L. including root bark, branches, leaves, and fruits, the root bark showed the most potent enzyme inhibitory activities. Therefore, the aim of this study was to evaluate the anti-AD activity of the M. alba root bark and its isolate compounds, including mulberrofuran G (1), albanol B (2), and kuwanon G (3) via inhibition of AChE, BChE, and BACE1. Compounds 1 and 2 showed strong AChE- and BChE-inhibitory activities; 1-3 showed significant BACE1 inhibitory activity. Based on the kinetic study with AChE and BChE, 2 and 3 showed noncompetitive-type inhibition; 1 showed mixed-type inhibition. Moreover, 1-3 showed mixed-type inhibition against BACE1. The molecular docking simulations of 1-3 demonstrated negative binding energies, indicating a high affinity to AChE and BACE1. The hydroxyl group of 1-3 formed hydrogen bond with the amino acid residues located at AChE and BACE1. Consequently, these results indicate that the root bark of M. alba and its active compounds might be promising candidates for preventive and therapeutic agents for AD.

Inhibitory Effects of Resveratrol Analogs on Mushroom Tyrosinase Activity

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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.

[Distribution of acetylcholinesterase activity in the digestive system of the gastropod molluscs Littorina littorea and Achatina fulica].

Science.gov (United States)

Zaĭtseva, O V; Kuznetsova, T V

2008-01-01

With the use of the histochemical procedure for the demonstration of acetylcholinesterase (AchE) activity, the distribution cholinergic regulatory elements was studied in the esophagus, the pharynx, the stomach, the liver (the digestive gland) and the intestine in sea and terrestrial gastropod molluscs that differed in their general organization level, lifestyle, habitat and feeding type. In both molluscs, all the parts of the digestive tract contained the significant amount of intraepithelial AchE-positive cells of the open type, single subepithelial neurons and the nervous fibers localized among the muscle cells of the wall of the organs. The basal processes of the AchE-positive intraepithelial cells were shown to form the intraepithelial nerve plexus and to pass under the epithelium. The peculiarities and common principles in the distribution of the nervous elements detected, their possible function and the regulatory role in the digestion in gastropod molluscs and other animals are discussed.

Inhibitory effect of flavonoids from citrus plants on Epstein-Barr virus activation and two-stage carcinogenesis of skin tumors.

Science.gov (United States)

Iwase, Y; Takemura, Y; Ju-ichi, M; Ito, C; Furukawa, H; Kawaii, S; Yano, M; Mou, X Y; Takayasu, J; Tokuda, H; Nishino, H

2000-06-01

To search for possible anti-tumor promoters, thirteen flavones (1-13) obtained from the peel of Citrus plants were examined for their inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation by a short-term in vitro assay. Of these flavones, 3,5,6,7,8,3',4'-heptamethoxyflavone (HPT) (13) exhibited significant inhibitory effects on the EBV-EA activation induced by the tumor promoter, 12-O-tetradecanoylphorbol 13-acetate (TPA). Further, compound 13 exhibited remarkable inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test.

Influence of thermodynamic parameter in Lanosterol 14alpha-demethylase inhibitory activity as antifungal agents: a QSAR approach.

Science.gov (United States)

Vasanthanathan, Poongavanam; Lakshmi, Manickavasagam; Arockia Babu, Marianesan; Kaskhedikar, Sathish Gopalrao

2006-06-01

A quantitative structure activity relationship, Hansch approach was applied on twenty compounds of chromene derivatives as Lanosterol 14alpha-demethylase inhibitory activity against eight fungal organisms. Various physicochemical descriptors and reported minimum inhibitory concentration values of different fungal organisms were used as independent variables and dependent variable respectively. The best models for eight different fungal organisms were first validated by leave-one-out cross validation procedure. It was revealed that thermodynamic parameters were found to have overall significant correlationship with anti fungal activity and these studies provide an insight to design new molecules.

Sublethal Effects of Insecticide Exposure on Megacopta cribraria (Fabricius) Nymphs: Key Biological Traits and Acetylcholinesterase Activity.

Science.gov (United States)

Miao, Jin; Reisig, Dominic D; Li, Guoping; Wu, Yuqing

2016-01-01

Megacopta cribraria F. (Hemiptera: Plataspidae), the kudzu bug, is an invasive insect pest of U.S. soybean. At present, insecticide application is the primary and most effective control option for M. cribraria In this study, the potential effects of sublethal and low-lethal concentrations (LC10 and LC40) of three common insecticides on key biological traits and acetylcholinesterase (AChE) activity of the treated nymphal stage of insect were assessed. The results show that the sublethal concentration of imidacloprid significantly reduced adult emergence rate of M. cribraria A low-lethal concentration of imidacloprid significantly increased nymphal development time, but significantly decreased adult emergence rate and adult longevity. Both sublethal and low-lethal concentrations of acephate caused an increase in nymphal development time and a reduction in adult emergence rate and adult longevity. Fecundity of females was significantly reduced only by exposure to low-lethal concentrations of acephate. Sublethal and low-lethal concentrations of bifenthrin increased nymphal development time, but significantly decreased adult emergence rate. In addition, we found that the AChE activity of M. cribraria was significantly increased only by LC40 imidacloprid, but strongly inhibited by acephate. © The Author 2016. Published by Oxford University Press on behalf of the Entomological Society of America.

Effects of Heat, pH, and Gamma Irradiation Treatments on Lipase Inhibitory Activity of Sargassum thunbergii Ethanol Extract

International Nuclear Information System (INIS)

Kim, D.H.; Kim, K.B.W.R.; Kim, M.J.; Sunwoo, C.; Jung, S.A.; Kim, H.J.; Jeong, D.H.; Ahn, D.H.; Kim, T.W.; Cho, Y.J.

2012-01-01

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)

Synthesis, Biological Evaluation and Molecular Modelling of 2′-Hydroxychalcones as Acetylcholinesterase Inhibitors

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Sri Devi Sukumaran

2016-07-01

Full Text Available A series of 2′-hydroxy- and 2′-hydroxy-4′,6′-dimethoxychalcones was synthesised and evaluated as inhibitors of human acetylcholinesterase (AChE. The majority of the compounds were found to show some activity, with the most active compounds having IC50 values of 40–85 µM. Higher activities were generally observed for compounds with methoxy substituents in the A ring and halogen substituents in the B ring. Kinetic studies on the most active compounds showed that they act as mixed-type inhibitors, in agreement with the results of molecular modelling studies, which suggested that they interact with residues in the peripheral anionic site and the gorge region of AChE.

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

Energy Technology Data Exchange (ETDEWEB)

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

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

International Nuclear Information System (INIS)

Flaskos, J.; Nikolaidis, E.; Harris, W.; Sachana, M.; Hargreaves, A.J.

2011-01-01

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

Inhibitory effect of Sphagnum palustre extract and its bioactive compounds on aromatase activity

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Hee Jeong Eom

2016-09-01

Full Text Available Sphagnum palustre (a moss has been traditionally used in Korea for the cure of several diseases such as cardiac pain and stroke. In this research, the inhibitory effect of S. palustre on aromatase (cytochrome P450 19, CYP19 activity was studied. [1β-3H] androstenedione was used as a substrate and incubated with S. palustre extract and recombinant human CYP19 in the presence of NADPH. S. palustre extract inhibited aromatase in a concentration-dependent manner (IC50 value: 36.4 ± 8.1 µg/mL. To elucidate the major compounds responsible for the aromatase inhibitory effects of S. palustre extract, nine compounds were isolated from the extract and tested for their inhibition of aromatase activity. Compounds 1, 6, and 7 displayed aromatase inhibition, while the inhibition by the other compounds was negligible.

Sempervivum davisii: phytochemical composition, antioxidant and lipase-inhibitory activities.

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Uzun, Yusuf; Dalar, Abdullah; Konczak, Izabela

2017-12-01

Sempervivum davisii Muirhead (Crassulaceae) is a traditional medicinal herb from Eastern Anatolia. To date the composition of phytochemicals and physiological properties of this herb were not subjected to any research. This study identifies compounds in S. davisii hydrophilic extracts and evaluates their potential biological properties. Ethanol-based lyophilized extracts were obtained from aerial parts of plant (10 g of ground dry plant material in 200 mL of acidified aqueous ethanol, shaken for 2 h at 22 °C with supernatant collected and freeze-dried under vacuum). Phytochemical composition was investigated by liquid chromatography mass spectrometry (LC-MS/MS, phenolics) and gas chromatography mass spectrometry (GC-MS, volatiles). Phenolic compounds were quantified by high-performance liquid chromatography (HPLC) and the Folin-Ciocalteu assay. Subsequently, antioxidant capacity [ferric reducing antioxidant power (FRAP), oxygen radical absorbance capacity (ORAC) assays] and enzyme inhibitory properties (isolated porcine pancreatic lipase) of the extracts were determined. Polyphenolic compounds were the main constituents of lyophilized extracts, among which kaempferol glycosides and quercetin hexoside dominated. The extracts exhibited potent antioxidant (FRAP values of 1925.2-5973.3 μM Fe 2+ /g DW; ORAC values of 1858.5-4208.7 μM Trolox Eq./g DW) and moderate lipase inhibitory (IC 50 : 11.6-2.96 mg/mL) activities. Volatile compounds (nonanal, dehydroxylinalool oxide isomers, 2-decenal, 2-undecenal, 2,6-di-tetr-butylphenol) were also found. Phenolic compounds with the dominating kaempferol and quercetin derivatives are the sources of potent antioxidant properties of S. davisii hydrophilic extracts. The extracts exhibit moderate inhibitory properties towards isolated pancreatic lipase.

Design, synthesis and evaluation of some N-methylenebenzenamine derivatives as selective acetylcholinesterase (AChE) inhibitor and antioxidant to enhance learning and memory.

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Shrivastava, Sushant K; Srivastava, Pavan; Upendra, T V R; Tripathi, Prabhash Nath; Sinha, Saurabh K

2017-02-15

Series of some 3,5-dimethoxy-N-methylenebenzenamine and 4-(methyleneamino)benzoic acid derivatives comprising of N-methylenebenzenamine nucleus were designed, synthesized, characterized, and assessed for their acetylcholinesterase (AChE), butyrylcholinesterase (BChE) inhibitory, and antioxidant activity thereby improving learning and memory in rats. The IC 50 values of all the compound along with standard were determined on AChE and BChE enzyme. The free radical scavenging activity was also assessed by in vitro DPPH (2,2-diphenyl-1-picryl-hydrazyl) and hydrogen peroxide radical scavenging assay. The selective inhibitions of all compounds were observed against AChE in comparison with standard donepezil. The enzyme kinetic study of the most active compound 4 indicated uncompetitive AChE inhibition. The docking studies of compound 4 exhibited the worthy interaction on active-site gorge residues Phe330 and Trp279 responsible for its high affinity towards AChE, whereas lacking of the BChE inhibition was observed due to a wider gorge binding site and absence of important aromatic amino acids interactions. The ex vivo study confirmed AChE inhibition abilities of compound 4 at brain site. Further, a considerable decrease in escape latency period of the compound was observed in comparison with standard donepezil through in vivo Spatial Reference Memory (SRM) and Spatial Working Memory (SWM) models which showed the cognition-enhancing potential of compound 4. The in vivo reduced glutathione (GSH) estimation on rat brain tissue homogenate was also performed to evaluate free radical scavenging activity substantiated the antioxidant activity in learning and memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

Description of two Enterococcus strains isolated from traditional Peruvian artisanal-produced cheeses with a bacteriocin-like inhibitory activity

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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.

Synthesis, crystal structures, fluorescence and xanthine oxidase inhibitory activity of pyrazole-based 1,3,4-oxadiazole derivatives

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Qi, De-Qiang; Yu, Chuan-Ming; You, Jin-Zong; Yang, Guang-Hui; Wang, Xue-Jie; Zhang, Yi-Ping

2015-11-01

A series of pyrazole-based 1,3,4-oxadiazole derivatives were rationally designed and synthesized in good yields by following a convenient route. All the newly synthesized molecules were fully characterized by IR, 1H NMR and elemental analysis. Eight compounds were structurally determined by single crystal X-ray diffraction analysis. The fluorescence properties of all the compounds were investigated in dimethyl sulfoxide media. In addition, these newly synthesized compounds were evaluated for in vitro inhibitory activity against commercial enzyme xanthine oxidase (XO) by measuring the formation of uric acid from xanthine. Among the compounds synthesized and tested, 3d and 3e were found to be moderate inhibitory activity against commercial XO with IC50 = 72.4 μM and 75.6 μM. The studies gave a new insight in further optimization of pyrazole-based 1,3,4-oxadiazole derivatives with excellent fluorescence properties and XO inhibitory activity.

Two Novel Bioactive Peptides from Antarctic Krill with Dual Angiotensin Converting Enzyme and Dipeptidyl Peptidase IV Inhibitory Activities.

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Ji, Wei; Zhang, Chaohua; Ji, Hongwu

2017-07-01

Inhibition of dipeptidyl peptidase IV (DPP-IV) and angiotensin converting enzyme (ACE) are considered useful in managing 2 often associated conditions: diabetes and hypertension. In this study, corolase PP was used to hydrolyze Antarctic krill protein. The hydrolysate (AKH) was isolated by ultrafiltration and purified by size-exclusion chromatography, ion exchange chromatography and reversed-phase high-performance liquid chromatography (RP-HPLC) sequentially. The in vitro inhibitory activities of all AKHs and several fractions obtained against ACE and DPP-IV were assessed. Two peptides, purified with dual-strength inhibitory activity against ACE and DPP-IV, were identified by TOF-MS/MS. Results indicated that not all fractions exhibited dual inhibitory activities of ACE and DPP-IV. The purified peptide Lys-Val-Glu-Pro-Leu-Pro had half-maximal inhibitory concentrations (IC 50 ) of 0.93±0.05 and 0.73±0.04 mg/mL against ACE and DPP-IV, respectively. The other peptide Pro-Ala-Leu had IC 50 values of 0.64±0.05 and 0.88±0.03 mg/mL against ACE and DPP-IV, respectively. This study firstly reported the sequences of dual bioactive peptides from Antarctic krill proteins, further provided new insights into the bioactive peptides responsible for the ACE and DPP-IV inhibitory activities from the Antarctic krill protein hydrolysate to manage hypertension and diabetes. © 2017 Institute of Food Technologists®.

Utilisation of rapeseed protein isolates for production of peptides with angiotensin I-converting enzyme (ACE-inhibitory activity

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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.

The frontal lobes and inhibitory function

International Nuclear Information System (INIS)

Konishi, Seiki

2011-01-01

Neuropsychological studies using traditional tasks of inhibitory functions, such as the Wisconsin card sorting test (WCST) and the Go/No-Go Task have revealed that the frontal lobe is responsible for several types of inhibitory functions. However, the detailed psychological nature of the inhibitory functions and the precise location of their critical foci within the frontal lobe remain to be investigated. Functional magnetic resonance imaging provides spatial and temporal resolution that allowed us to illuminate at least 4 frontal regions involved in inhibitory functions: the dorsolateral, ventrolateral, and rostral parts of the frontal lobe and the presupplementary motor area (preSMA). The ventrolateral part of the frontal lobe in the right hemisphere was activated during response inhibition. The preSMA in the left hemisphere was activated during inhibition of proactive interference immediately after the dimension changes of the WCST. The rostral part of the frontal lobe in the left hemisphere was activated during inhibition long after the dimension changes. The dorsolateral part of the frontal lobe in the left hemisphere was activated at the dimension changes in the first time, but not in the second time. These findings provide clues to our understanding of functional differentiation of inhibitory functions and their localization in the frontal lobe. (author)

Triterpenoids from Azorella trifurcata (Gaertn.) Pers and their effect against the enzyme acetylcholinesterase

Energy Technology Data Exchange (ETDEWEB)

Areche, Carlos; Cejas, Patricia; Thomas, Pablo; San-Martin, Aurelio [University of Chile, Santiago (Chile). Faculty of Sciences. Dept. of Chemistry], e-mail: aurelio@uchile.cl; Astudillo, Luis; Gutierrez, Margarita [University of Talca, Talca (Chile). Inst. of Chemistry of Natural Resource; Loyola, Luis A. [University of Antofagasta (Chile). Faculty of Basic Sciences. Dept. of Chemistry

2009-07-01

The inhibition of the enzyme acetylcholinesterase is considered as a strategy for the treatment of Alzheimer's disease, senile dementia, ataxia, and myasthenia gravis. Three lanostane- and two cycloartane-type triterpenes, together with two mulinane-type diterpenes were isolated from petroleum ether extract of the whole shrub of Azorella trifurcata (Gaertn.) Pers. Their effect on the enzyme acetylcholinesterase was assessed as well. In addition, this is the first report of these triterpenes in the genus Azorella. (author)

Triterpenoids from Azorella trifurcata (Gaertn.) Pers and their effect against the enzyme acetylcholinesterase

International Nuclear Information System (INIS)

Areche, Carlos; Cejas, Patricia; Thomas, Pablo; San-Martin, Aurelio; Astudillo, Luis; Gutierrez, Margarita; Loyola, Luis A.

2009-01-01

The inhibition of the enzyme acetylcholinesterase is considered as a strategy for the treatment of Alzheimer's disease, senile dementia, ataxia, and myasthenia gravis. Three lanostane- and two cycloartane-type triterpenes, together with two mulinane-type diterpenes were isolated from petroleum ether extract of the whole shrub of Azorella trifurcata (Gaertn.) Pers. Their effect on the enzyme acetylcholinesterase was assessed as well. In addition, this is the first report of these triterpenes in the genus Azorella. (author)

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

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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.

Identification of diphtheria toxin R domain mutants with enhanced inhibitory activity against HB-EGF.

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Suzuki, Keisuke; Mizushima, Hiroto; Abe, Hiroyuki; Iwamoto, Ryo; Nakamura, Haruki; Mekada, Eisuke

2015-05-01

Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a ligand of EGF receptor, is involved in the growth and malignant progression of cancers. Cross-reacting material 197, CRM197, a non-toxic mutant of diphtheria toxin (DT), specifically binds to the EGF-like domain of HB-EGF and inhibits its mitogenic activity, thus CRM197 is currently under evaluation in clinical trials for cancer therapy. To develop more potent DT mutants than CRM197, we screened various mutant proteins of R domain of DT, the binding site for HB-EGF. A variety of R-domain mutant proteins fused with maltose-binding protein were produced and their inhibitory activity was evaluated in vitro. We found four R domain mutants that showed much higher inhibitory activity against HB-EGF than wild-type (WT) R domain. These R domain mutants suppressed HB-EGF-dependent cell proliferation more effectively than WT R domain. Surface plasmon resonance revealed their higher affinity to HB-EGF than WT R domain. CRM197(R460H) carrying the newly identified mutation showed increased cell proliferation inhibitory activity and affinity to HB-EGF. These results suggest that CRM197(R460H) or other recombinant proteins carrying newly identified mutation(s) in the R domain are potential therapeutics targeting HB-EGF. © The Authors 2014. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

Antioxidant and enzyme inhibitory activities of Plebeian herba (Salvia plebeia R. Br.) under different cultivation conditions.

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Chen, Lei; Kang, Young-Hwa

2014-03-12

An adaptation of cultural management to the specific cultural system, as well as crop demand, can further result in the improvement of the quality of horticultural products. Therefore, this study focused on the antioxidant and enzyme inhibitory activities of Plebeian herba (Salvia plebeia R. Br.) grown in hydroponics in comparison with those of the plant grown in soil. The antioxidant activities of Plebeian herba extract were measured as 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging abilities as well as the reducing power by decreasing nitric oxide (NO) and superoxide dismutase activity (SOD) in vitro. Interestingly, by comparison with hydroponics and traditional cultivation, Plebeian herba cultivated in nutrition-based soil improved inhibitory effect on free radicals of DPPH, ABTS, and NO and increased the contents of phenolics such as caffeic acid (1), luteolin-7-glucoside (2), homoplantaginin (3), hispidulin (4), and eupatorin. Free radical scavenging and SOD activity, as well as α-glucosidase inhibitory effect, were higher in Plebeian herba grown in nutrition-based soil than in plants grown in hydroponics and traditional condition.

Death and rebirth of neural activity in sparse inhibitory networks

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Angulo-Garcia, David; Luccioli, Stefano; Olmi, Simona; Torcini, Alessandro

2017-05-01

Inhibition is a key aspect of neural dynamics playing a fundamental role for the emergence of neural rhythms and the implementation of various information coding strategies. Inhibitory populations are present in several brain structures, and the comprehension of their dynamics is strategical for the understanding of neural processing. In this paper, we clarify the mechanisms underlying a general phenomenon present in pulse-coupled heterogeneous inhibitory networks: inhibition can induce not only suppression of neural activity, as expected, but can also promote neural re-activation. In particular, for globally coupled systems, the number of firing neurons monotonically reduces upon increasing the strength of inhibition (neuronal death). However, the random pruning of connections is able to reverse the action of inhibition, i.e. in a random sparse network a sufficiently strong synaptic strength can surprisingly promote, rather than depress, the activity of neurons (neuronal rebirth). Thus, the number of firing neurons reaches a minimum value at some intermediate synaptic strength. We show that this minimum signals a transition from a regime dominated by neurons with a higher firing activity to a phase where all neurons are effectively sub-threshold and their irregular firing is driven by current fluctuations. We explain the origin of the transition by deriving a mean field formulation of the problem able to provide the fraction of active neurons as well as the first two moments of their firing statistics. The introduction of a synaptic time scale does not modify the main aspects of the reported phenomenon. However, for sufficiently slow synapses the transition becomes dramatic, and the system passes from a perfectly regular evolution to irregular bursting dynamics. In this latter regime the model provides predictions consistent with experimental findings for a specific class of neurons, namely the medium spiny neurons in the striatum.

A Comparative Analysis of Perinatal Development of Barrel Cortex in Rat, Mouse and Guinea Pig Using Acetylcholinesterase Histochemistry

OpenAIRE

ŞENDEMİR, Erdoğan

2014-01-01

The role of acetylcholinesterase (AChE) in the developing neocortex was reexamined by comparing its expression in rats, mice and guinea pigs, following the protocol for acetylcholinesterase histochemistry (described in Sendemir et al., 1996) in order to determine the suitability of the breeding colony at UludaÛ University for use as an animal model. A total of 103 pups as well as two adult animals of each species were used. In the rat pups, acetylcholinesterase-rich patches were d...

Discovery of aliphatic-chain hydroxamates containing indole derivatives with potent class I histone deacetylase inhibitory activities.

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Chao, Shi-Wei; Chen, Liang-Chieh; Yu, Chia-Chun; Liu, Chang-Yi; Lin, Tony Eight; Guh, Jih-Hwa; Wang, Chen-Yu; Chen, Chun-Yung; Hsu, Kai-Cheng; Huang, Wei-Jan

2018-01-01

Histone deacetylase (HDAC) is a validated drug target for various diseases. This study combined indole recognition cap with SAHA, an FDA-approved HDAC inhibitor used to treat cutaneous T-cell lymphoma (CTCL). The structure activity relationship of the resulting compounds that inhibited HDAC was disclosed as well. Some compounds exhibited much stronger inhibitory activities than SAHA. We identified two meta-series compounds 6j and 6k with a two-carbon linker had IC 50 values of 3.9 and 4.5 nM for HDAC1, respectively. In contrast, the same oriented compounds with longer carbon chain linkers showed weaker inhibition. The result suggests that the linker chain length greatly contributed to enzyme inhibitory potency. In addition, comparison of enzyme-inhibiting activity between the compounds and SAHA showed that compounds 6j and 6k displayed higher inhibiting activity for class I (HDAC1, -2, -3 and -8). The molecular docking and structure analysis revealed structural differences with the inhibitor cap and metal-binding regions between the HDAC isozymes that affect interactions with the inhibitors and play a key role for selectivity. Further biological evaluation showed multiple cellular effects associated with compounds 6j- and 6k-induced HDAC inhibitory activity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Inhibitory Effect and Mechanism of Arctium lappa Extract on NLRP3 Inflammasome Activation

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Young-Kyu Kim

2018-01-01

Full Text Available Arctium lappa (A. lappa, Compositae, is considered a potential source of nutrition and is used as a traditional medicine in East Asian countries for centuries. Although several studies have shown its biological activities as an anti-inflammatory agent, there have been no reports on A. lappa with regard to regulatory role in inflammasome activation. The purpose of this study was to investigate the inhibitory effects of A. lappa extract (ALE on NLRP3 inflammasome activation and explore the underlying mechanisms. We found that ALE inhibited IL-1β secretion from NLRP3 inflammasome activated bone marrow derived macrophages but not that secreted by NLRC4 and AIM2 inflammasomes activation. Mechanistic studies revealed that ALE suppressed the ATPase activity of purified NLRP3 and reduced mitochondrial reactive oxygen species (mROS generated during NLRP3 activation. Therefore, the inhibitory effect of ALE on NLRP3 inflammasome might be attributed to its ability to inhibit the NLRP3 ATPase function and attenuated the mROS during inflammasome activation. In addition, ALE significantly reduced the LPS-induced increase of plasma IL-1β in mouse peritonitis model. These results provide evidence of novel anti-inflammatory mechanisms of A. lappa, which might be used for therapeutic applications in the treatment of NLRP3 inflammasome-associated inflammatory disorders.

Chemical composition and α-amylase inhibitory activity of the essential oil from Sabina chinensis cv. Kaizuca leaves.

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Gu, Dongyu; Fang, Chen; Yang, Jiao; Li, Minjing; Liu, Hengming; Yang, Yi

2018-03-01

Sabina chinensis cv. Kaizuca (SCK) is a variant of S. chinensis L. The essential oil from its leaves exhibited α-amylase inhibitory activity in vitro and the IC 50 value was 187.08 ± 0.56 μg/mL. Nineteen compounds were identified from this essential oil by gas chromatography-mass spectrometry (GC-MS) analysis. The major compounds identified were bornyl acetate (42.6%), elemol (20.5%), β-myrcene (13.7%) and β-linalool (4.0%). In order to study the reason of the α-amylase inhibitory activity of this essential oil, the identified compounds were docked with α-amylase by molecular docking individually. Among these compounds, γ-eudesmol exhibited the lowest binding energy (-6.73 kcal/mol), followed by α-copaen-11-ol (-6.66 kcal/mol), cubedol (-6.39 kcal/mol) and α-acorenol (-6.12 kcal/mol). The results indicated that these compounds were the active ingredients responsible for the α-amylase inhibitory activity of essential oil from SCK.

Inhibitory Activity of Yokukansankachimpihange against Nerve Growth Factor-Induced Neurite Growth in Cultured Rat Dorsal Root Ganglion Neurons

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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.

Effects of hyper- and hypothyroidism on acetylcholinesterase, (Na(+), K (+))- and Mg ( 2+ )-ATPase activities of adult rat hypothalamus and cerebellum.

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Carageorgiou, Haris; Pantos, Constantinos; Zarros, Apostolos; Stolakis, Vasileios; Mourouzis, Iordanis; Cokkinos, Dennis; Tsakiris, Stylianos

2007-03-01

Thyroid hormones (THs) are recognized as key metabolic hormones, and the metabolic rate increases in hyperthyroidism, while it decreases in hypothyroidism. The aim of this work was to investigate how changes in metabolism induced by THs could affect the activities of acetylcholinesterase (AChE), (Na(+), K(+))- and Mg(2+)-ATPase in the hypothalamus and the cerebellum of adult rats. Hyperthyroidism was induced by subcutaneous administration of thyroxine (25 microg/100 g body weight) once daily for 14 days, while hypothyroidism was induced by oral administration of propylthiouracil (0.05%) for 21 days. All enzyme activities were evaluated spectrophotometrically in the homogenated brain regions of 10 three-animal pools. Neither hyper-, nor hypothyroidism had any effect on the examined hypothalamic enzyme activities. In the cerebellum, hyperthyroidism provoked a significant decrease in both the AChE (-23%, p activities (-26%, p activities: AChE (-17%, p activity was found unaltered in both the hyper- and the hypothyroid brain regions. neither hyper-, nor hypothyroidism had any effect on the examined hypothalamic enzyme activities. In the cerebellum, hyperthyroidism provoked a significant decrease in both the AChE and the Na(+), K(+)-ATPase activities. The decreased (by the THs) Na(+), K(+)-ATPase activities may increase the synaptic acetylcholine release, and thus, could result in a decrease in the cerebellar AChE activity. Moreover, the above TH-induced changes may affect the monoamine neurotransmitter systems.

Fenugreek hydrogel–agarose composite entrapped gold nanoparticles for acetylcholinesterase based biosensor for carbamates detection

Energy Technology Data Exchange (ETDEWEB)

Kestwal, Rakesh Mohan; Bagal-Kestwal, Dipali; Chiang, Been-Huang, E-mail: bhchiang@ntu.edu.tw

2015-07-30

A biosensor was fabricated to detect pesticides in food samples. Acetylcholinesterase was immobilized in a novel fenugreek hydrogel–agarose matrix with gold nanoparticles. Transparent thin films with superior mechanical strength and stability were obtained with 2% fenugreek hydrogel and 2% agarose. Immobilization of acetylcholinesterase on the membrane resulted in high enzyme retention efficiency (92%) and a significantly prolonged shelf life of the enzyme (half-life, 55 days). Transmission electron microscopy revealed that, gold nanoparticles (10–20 nm in diameter) were uniformly dispersed in the fenugreek hydrogel–agarose–acetylcholinesterase membrane. This immobilized enzyme-gold nanoparticle dip-strip system detected various carbamates, including carbofuran, oxamyl, methomyl, and carbaryl, with limits of detection of 2, 21, 113, and 236 nM (S/N = 3), respectively. Furthermore, the fabricated biosensor exhibited good testing capabilities when used to detect carbamates added to various fruit and vegetable samples. - Highlights: • Acetylcholinesterase (AChE) dip-strip biosensor fabricated to detect carbamates. • AChE entrapped in fenugreek hydrogel–agarose matrix with gold nanoparticles (GNPs). • High enzyme retention efficiency (92%) and shelf life (half-life, 55 days). • Detection limits of carbofuran, oxamyl and methomyl: 2, 21 and 113 nM. • The biosensor had good testing capabilities to detect carbamates in food samples.

Hairy-root organ cultures for the production of human acetylcholinesterase

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Mor Tsafrir S

2008-12-01

Full Text Available Abstract Background Human cholinesterases can be used as a bioscavenger of organophosphate toxins used as pesticides and chemical warfare nerve agents. The practicality of this approach depends on the availability of the human enzymes, but because of inherent supply and regulatory constraints, a suitable production system is yet to be identified. Results As a promising alternative, we report the creation of "hairy root" organ cultures derived via Agrobacterium rhizogenes-mediated transformation from human acetylcholinesterase-expressing transgenic Nicotiana benthamiana plants. Acetylcholinesterase-expressing hairy root cultures had a slower growth rate, reached to the stationary phase faster and grew to lower maximal densities as compared to wild type control cultures. Acetylcholinesterase accumulated to levels of up to 3.3% of total soluble protein, ~3 fold higher than the expression level observed in the parental plant. The enzyme was purified to electrophoretic homogeneity. Enzymatic properties were nearly identical to those of the transgenic plant-derived enzyme as well as to those of mammalian cell culture derived enzyme. Pharmacokinetic properties of the hairy-root culture derived enzyme demonstrated a biphasic clearing profile. We demonstrate that master banking of plant material is possible by storage at 4°C for up to 5 months. Conclusion Our results support the feasibility of using plant organ cultures as a successful alternative to traditional transgenic plant and mammalian cell culture technologies.

DC-159a Shows Inhibitory Activity against DNA Gyrases of Mycobacterium leprae.

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Yamaguchi, Tomoyuki; Yokoyama, Kazumasa; Nakajima, Chie; Suzuki, Yasuhiko

2016-09-01

Fluoroquinolones are a class of antibacterial agents used for leprosy treatment. Some new fluoroquinolones have been attracting interest due to their remarkable potency that is reportedly better than that of ofloxacin, the fluoroquinolone currently recommended for treatment of leprosy. For example, DC-159a, a recently developed 8-methoxy fluoroquinolone, has been found to be highly potent against various bacterial species. Nonetheless, the efficacy of DC-159a against Mycobacterium leprae is yet to be examined. To gather data that can support highly effective fluoroquinolones as candidates for new remedies for leprosy treatment, we conducted in vitro assays to assess and compare the inhibitory activities of DC-159a and two fluoroquinolones that are already known to be more effective against M. leprae than ofloxacin. The fluoroquinolone-inhibited DNA supercoiling assay using recombinant DNA gyrases of wild type and ofloxacin-resistant M. leprae revealed that inhibitory activities of DC-159a and sitafloxacin were at most 9.8- and 11.9-fold higher than moxifloxacin. Also the fluoroquinolone-mediated cleavage assay showed that potencies of those drugs were at most 13.5- and 9.8-fold higher than moxifloxacin. In addition, these two drugs retained their inhibitory activities even against DNA gyrases of ofloxacin-resistant M. leprae. The results indicated that DC-159a and sitafloxacin are more effective against wild type and mutant M. leprae DNA gyrases than moxifloxacin, suggesting that these antibacterial drugs can be good candidates that may supersede current fluoroquinolone remedies. DC-159a in particular is very promising because it is classified in a subgroup of fluoroquinolones that is known to be less likely to cause adverse effects. Our results implied that DC-159a is well worth further investigation to ascertain its in vivo effectiveness and clinical safety for humans.

Soluble epoxide hydrolase inhibitory activity of anthraquinone components from Aloe.

Science.gov (United States)

Sun, Ya Nan; Kim, Jang Hoon; Li, Wei; Jo, A Reum; Yan, Xi Tao; Yang, Seo Young; Kim, Young Ho

2015-10-15

Aloe is a short-stemmed succulent herb widely used in traditional medicine to treat various diseases and as raw material in cosmetics and heath foods. In this study, we isolated and identified two new anthraquinone derivatives, aloinoside C (6) and aloinoside D (7), together with six known compounds from an aqueous dissolved Aloe exudate. Their structures were identified by spectroscopic analysis. The inhibitory effects of the isolated compounds on soluble epoxide hydrolase (sEH) were evaluated. Compounds 1-8 inhibited sEH activity potently, with IC50 values ranging from 4.1±0.6 to 41.1±4.2 μM. A kinetic analysis of compounds 1-8 revealed that the inhibitory actions of compounds 1, 6 and 8 were non-competitive, whereas those of compounds 2-5 and 7 were the mixed-type. Molecular docking increases our understanding of receptor-ligand binding of all compounds. These results demonstrate that compounds 1-8 from Aloe are potential sEH inhibitors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Novel and viable acetylcholinesterase target site for developing effective and environmentally safe insecticides.

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Pang, Yuan-Ping; Brimijoin, Stephen; Ragsdale, David W; Zhu, Kun Yan; Suranyi, Robert

2012-04-01

Insect pests are responsible for human suffering and financial losses worldwide. New and environmentally safe insecticides are urgently needed to cope with these serious problems. Resistance to current insecticides has resulted in a resurgence of insect pests, and growing concerns about insecticide toxicity to humans discourage the use of insecticides for pest control. The small market for insecticides has hampered insecticide development; however, advances in genomics and structural genomics offer new opportunities to develop insecticides that are less dependent on the insecticide market. This review summarizes the literature data that support the hypothesis that an insect-specific cysteine residue located at the opening of the acetylcholinesterase active site is a promising target site for developing new insecticides with reduced off-target toxicity and low propensity for insect resistance. These data are used to discuss the differences between targeting the insect-specific cysteine residue and targeting the ubiquitous catalytic serine residue of acetylcholinesterase from the perspective of reducing off-target toxicity and insect resistance. Also discussed is the prospect of developing cysteine-targeting anticholinesterases as effective and environmentally safe insecticides for control of disease vectors, crop damage, and residential insect pests within the financial confines of the present insecticide market.

Trypsin inhibitory activity of artemisinin and its biotransformed product

International Nuclear Information System (INIS)

Shahwar, D.; Raza, M.A.

2013-01-01

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)

Antibacterial and EGFR-Tyrosine Kinase Inhibitory Activities of Polyhydroxylated Xanthones from Garcinia succifolia

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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.

Acetylcholinesterase concentrations in heparinized blood of Hispaniolan Amazon parrots (Amazona ventralis).

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Tully, Thomas N; Osofsky, Anna; Jowett, Peter L H; Hosgood, Giselle

2003-12-01

Organophosphate and carbamate pesticides inhibit acetylcholinesterase (AChE) at nerve synapses. Blood samples from 22 Hispaniolan Amazon parrots (Amazona ventralis) were assayed for cholinesterase levels by two different techniques. Using the modified Michel method, the whole-blood cholinesterase activity levels ranged from 0.082 to 0.616 deltapH/hr with a mean value of 0.35 deltapH/hr. A reference range (0.08-0.62 deltapH/hr) for cholinesterase was established in birds. The modified Ellman spectrophotometric method was used to measure AChE activity by adding acetylthiocholine or pseudocholinesterase (plasma cholinesterase) activity by adding butyrylthiocholine. The reference range of the AChE activity using the modified Ellman spectrophotometric method was 0-1.12 micromol/ml/min with a mean of 0.48 micromol/ml/min, and for pseudocholinesterase the range was 0.09-0.98 micromol/ml/min with a mean of 0.53 micromol/ml/min.

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

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

2014-01-10

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

Interactions of p-Nitrobenzene Diazonium Fluoroborate and Analogs with the Active Sites of Acetylcholine-Receptor and -Esterase*

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Mautner, Henry G.; Bartels, Eva

1970-01-01

p-Nitrobenzene diazonium fluoroborate (NDF) is a potent inhibitor of the carbamylcholine-induced depolarization of the electroplax and of acetylcholinesterase. It probably forms covalent bonds with the acetylcholine-receptor and -esterase at the active site of the proteins. Its inhibitory strength is at least the same as that of trimethylammonium diazonium fluoroborate (TDF). The p-acetoxy analog, with its weaker electron-withdrawing group, is about ten times weaker as an inhibitor than the trimethylammonium or p-nitro analogs, both of which have strong electron-withdrawing groups. After treatment of the electroplax preparation with dithiothreitol, NDF remains an irreversible receptor-inhibitor, while TDF becomes a potent reversible receptor-activator. TDF is self-inhibitory: applied before reduction, it no longer depolarizes. Although the first observations on TDF suggested that the compound labels both proteins by virtue of the steric complementary of its trimethylammonium group to a negative subsite in the proteins, the present study indicates that it is the positively charged diazonium group that reacts with the active sites of the proteins to form a covalent bond with an appropriate amino-acid residue. PMID:5272331

Polyphenols isolated from Acacia mearnsii bark with anti-inflammatory and carbolytic enzyme inhibitory activities

Institute of Scientific and Technical Information of China (English)

XIONG Jia; GRACE Mary H; ESPOSITO Debora; KOMARNYTSKY Slavko; WANG Fei; LILA Mary Ann

2017-01-01

The present study was designed to characterize the polyphenols isolated from Acacia mearnsii bark crude extract (B) and fractions (B1-B7) obtained by high-speed counter-current chromatography (HSCCC) and evaluate their anti-inflammatory and carbolytic enzymes (α-glucosidase and α-amylase) inhibitory activities.Fractions B4,B5,B6,B7 (total phenolics 850.3,983.0,843.9,and 572.5 mg·g-1,respectively;proanthocyanidins 75.7,90.5,95.0,and 44.8 mg·g-1,respectively) showed significant activities against reactive oxygen species (ROS),nitric oxide (NO) production,and expression of pro-inflammatory genes interleukin-lβ (IL-1β) and inducible nitric oxide synthase (iNOS) in a lipopolysaccharide (LPS)-stimulated mouse macrophage cell line RAW 264.7.All the extracts suppressed α-glucosidase and α-amylase activities,two primary enzymes responsible for carbohydrate digestion.A.mearnsii bark samples possessed significantly stronger inhibitory effects against α-glucosidase enzyme (IC50 of 0.4-1.4 tg·mL-1) than the pharmaceutical acarbose (IC50 141.8 μg·mL-1).B6 and B7 (IC5017.6 and 11.7 μg·mL-1,respectively) exhibited α-amylase inhibitory activity as efficacious as acarbose (IC50 15.4 μg·mL-1).Moreover,B extract,at 25 μg·mL-l,significantly decreased the non-mitochondrial oxidative burst that is often associated with inflammatory response in human monocytic macrophages.

Antioxidant, xanthine oxidase and lipoxygenase inhibitory activities and phenolics of Bauhinia rufescens Lam. (Caesalpiniaceae).

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Compaoré, M; Lamien, C E; Lamien-Meda, A; Vlase, L; Kiendrebeogo, M; Ionescu, C; Nacoulma, O G

2012-01-01

An aqueous acetone extract of the stem with the leaves of Bauhinia rufescens and its fractions were analysed for their antioxidant and enzyme-inhibitory activities, as well as their phytochemical composition. For measurement of the antioxidant activities, the 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzoline-6-sulphonate) and the ferric-reducing methods were used. The results indicated that the aqueous acetone, its ethyl acetate and n-butanol fractions possessed considerable antioxidant activity. Further, the xanthine oxidase and lipoxygenase inhibitory assays showed that the n-butanol fraction possessed compounds that can inhibit both these enzymes. In the phytochemical analysis, the ethyl acetate and the n-butanol fractions of the aqueous acetone extract were screened by HPLC-MS for their phenolic content. The results indicated the presence of hyperoside, isoquercitrin, rutin quercetin, quercitrin, p-coumaric and ferulic acids in the non-hydrolysed fractions. In the hydrolysed fractions, kaempferol, p-coumaric and ferulic acids were identified.

Chemical modification, antioxidant and α-amylase inhibitory activities of corn silk polysaccharides.

Science.gov (United States)

Chen, Shuhan; Chen, Haixia; Tian, Jingge; Wang, Yanwei; Xing, Lisha; Wang, Jia

2013-10-15

Water-soluble corn silk polysaccharides (CSPS) were chemically modified to obtain their sulfated, acetylated and carboxymethylated derivatives. Chemical characterization and bioactivities of CSPS and its derivatives were comparatively investigated by chemical methods, gas chromatography, gel filtration chromatography, scanning electron microscope, infrared spectroscopy and circular dichroism spectroscopy, scavenging DPPH free radical assay, scavenging hydroxyl radical assay, ferric reducing power assay, lipid peroxidation inhibition assay and α-amylase activity inhibitory assay, respectively. Among the three derivatives, carboxylmethylated polysaccharide (C-CSPS) demonstrated higher solubility, narrower molecular weight distribution, lower intrinsic viscosity, a hyperbranched conformation, significantly higher antioxidant and α-amylase inhibitory abilities compared with the native polysaccharide and other derivatives. C-CSPS might be used as a novel nutraceutical agent for human consumption. Copyright © 2013 Elsevier Ltd. All rights reserved.

Inhibitory Effects of Standardized Extracts of Phyllanthus amarus and Phyllanthus urinaria and Their Marker Compounds on Phagocytic Activity of Human Neutrophils

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Yuandani

2013-01-01

Full Text Available The standardized methanol extracts of Phyllanthus amarus and P. urinaria, collected from Malaysia and Indonesia, and their isolated chemical markers, phyllanthin and hypophyllanthin, were evaluated for their effects on the chemotaxis, phagocytosis and chemiluminescence of human phagocytes. All the plant extracts strongly inhibited the migration of polymorphonuclear leukocytes (PMNs with the Malaysian P. amarus showing the strongest inhibitory activity (IC50 value, 1.1 µg/mL. There was moderate inhibition by the extracts of the bacteria engulfment by the phagocytes with the Malaysian P. amarus exhibiting the highest inhibition (50.8% of phagocytizing cells. The Malaysian P. amarus and P. urinaria showed strong reactive oxygen species (ROS inhibitory activity, with both extracts exhibiting IC50 value of 0.7 µg/mL. Phyllanthin and hypophyllanthin exhibited relatively strong activity against PMNs chemotaxis, with IC50 values slightly lower than that of ibuprofen (1.4 µg/mL. Phyllanthin exhibited strong inhibitory activity on the oxidative burst with an IC50 value comparable to that of aspirin (1.9 µg/mL. Phyllanthin exhibited strong engulfment inhibitory activity with percentage of phagocytizing cells of 14.2 and 27.1% for neutrophils and monocytes, respectively. The strong inhibitory activity of the extracts was due to the presence of high amounts of phyllanthin and hypophyllanthin although other constituents may also contribute.

New 5-deoxyflavonoids and their inhibitory effects on protein tyrosine phosphatase 1B (PTP1B) activity

DEFF Research Database (Denmark)

Nguyen, Phi Hung; Dao, Trong Tuan; Kim, Jayeon

2011-01-01

.9 ± 1.6 to 19.2 ± 1.1 μM), while compounds (3, 5, and 9) with 2,2-dimethylpyrano ring showed less inhibitory effect (IC₅₀ 22.6 ± 2.3 to 72.9 ± 9.7 μM). These results suggest that prenyl and methoxy groups may be responsible for the increase on the activity of 5-deoxyflavonoids against PTP1B......, but the presence of 2,2-dimethylpyrano ring on the B ring may be induced the decrease of PTP1B inhibitory activity....

Identification of Potential Herbal Inhibitor of Acetylcholinesterase Associated Alzheimer’s Disorders Using Molecular Docking and Molecular Dynamics Simulation

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Chandrabhan Seniya

2014-01-01

Full Text Available Cholinesterase inhibitors (ChE-Is are the standard for the therapy of AD associated disorders and are the only class of approved drugs by the Food and Drug Administration (FDA. Additionally, acetylcholinesterase (AChE is the target for many Alzheimer’s dementia drugs which block the function of AChE but have some side effects. Therefore, in this paper, an attempt was made to elucidate cholinesterase inhibition potential of secondary metabolite from Cannabis plant which has negligible or no side effect. Molecular docking of 500 herbal compounds, against AChE, was performed using Autodock 4.2 as per the standard protocols. Molecular dynamics simulations have also been carried out to check stability of binding complex in water for 1000 ps. Our molecular docking and simulation have predicted high binding affinity of secondary metabolite (C28H34N2O6 to AChE. Further, molecular dynamics simulations for 1000 ps suggest that ligand interaction with the residues Asp72, Tyr70-121-334, and Phe288 of AChE, all of which fall under active site/subsite or binding pocket, might be critical for the inhibitory activity of AChE. This approach might be helpful to understand the selectivity of the given drug molecule in the treatment of Alzheimer's disease. The study provides evidence for consideration of C28H34N2O6 as a valuable small ligand molecule in treatment and prevention of AD associated disorders and further in vitro and in vivo investigations may prove its therapeutic potential.

UHPLC-ESI-ORBITRAP-MS analysis of the native Mapuche medicinal plant palo negro (Leptocarpha rivularis DC. - Asteraceae) and evaluation of its antioxidant and cholinesterase inhibitory properties.

Science.gov (United States)

Jiménez-González, Andrea; Quispe, Cristina; Bórquez, Jorge; Sepúlveda, Beatriz; Riveros, Felipe; Areche, Carlos; Nagles, Edgar; García-Beltrán, Olimpo; Simirgiotis, Mario J

2018-12-01

UHPLC/ESI/MS identification of organic compounds is the first step in the majority of screening techniques for the characterization of biologically active metabolites in natural sources. This paper describes a method for the fast identification and characterisation of secondary metabolites in Leptocarpha rivularis DC. (Palo negro) extracts by HPLC/UV (DAD)-Mass Spectrometry (HPLC/MS). The plant is used for the treatment of several diseases since pre-hispanic Mapuche times. Thirty-seven compounds were detected in the aqueous edible extract for the first time including 4 sesquiterpenes, 10 flavonoids, 9 oxylipins, 2 organic acids, and 11 phenolic acids. In addition, phenolic content antioxidant and cholinesterase inhibitory activities were measured for the first time using the edible infusion. The total polyphenol content of the infusion was 230.76 ± 2.5 mmol GAE/kg dry weight, while the antioxidant activity was 176.51 ± 28.84; 195.28 ± 4.83; and 223.92 ± 2.95 mmol TE/kg dry weight, for the DPPH, ABTS, and FRAP assays, respectively. The cholinesterase inhibitory activity was 7.38 ± 0.03 and 5.74 ± 0.06 mmol GALAE/kg, for the inhibition of acetylcholinesterase AChE and BChE, respectively, showing that this plant is a candidate for the isolation of compounds that can be useful for the treatment of neurodegenerative diseases. Furthermore, this plant could serve also as a raw material for the production of dietary supplements, due to its content of polyphenolic compounds.

In silico docking studies of aldose reductase inhibitory activity of commercially available flavonoids

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Arumugam Madeswaran

2012-12-01

Full Text Available The primary objective of this study was to investigate the aldose reductase inhibitory activity of flavonoids using in silico docking studies. In this perspective, flavonoids like biochanin, butein, esculatin, fisetin and herbacetin were selected. Epalrestat, a known aldose reductase inhibitor was used as the standard. In silico docking studies were carried out using AutoDock 4.2, based on the Lamarckian genetic algorithm principle. The results showed that all the selected flavonoids showed binding energy ranging between -9.33 kcal/mol to -7.23 kcal/mol when compared with that of the standard (-8.73 kcal/mol. Inhibition constant (144.13 µM to 4.98 µM and intermolecular energy (-11.42 kcal/mol to -7.83 kcal/mol of the flavonoids also coincide with the binding energy. All the selected flavonoids contributed aldose reductase inhibitory activity because of its structural properties. These molecular docking analyses could lead to the further development of potent aldose reductase inhibitors for the treatment of diabetes.

Bifunctional phenolic-choline conjugates as anti-oxidants and acetylcholinesterase inhibitors

Czech Academy of Sciences Publication Activity Database

Šebestík, Jaroslav; Marques, S. M.; Falé, P. L.; Santos, S.; Arduíno, D. M.; Cardoso, S. M.; Oliveira, S. M.; Serralheiro, M. L. M.; Santos, A. M.

Roč. 26, č. 4 (485), s. 497 ISSN 1475-6366 Institutional research plan: CEZ:AV0Z40550506 Keywords : acetylcholinesterase inhibitors * antioxidants * hybrid ligands * anti-neurodegeneratives * Alzheimer´s disease Subject RIV: CC - Organic Chemistry

Bacteriocin-like inhibitory activities of seven Lactobacillus delbrueckii subsp. bulgaricus strains against antibiotic susceptible and resistant Helicobacter pylori strains.

Science.gov (United States)

Boyanova, L; Gergova, G; Markovska, R; Yordanov, D; Mitov, I

2017-12-01

The aim of the study was to detect anti-Helicobacter pylori activity of seven Lactobacillus delbrueckii subsp. bulgaricus (GLB) strains by four cell-free supernatant (CFS) types. Activity of non-neutralized and non-heat-treated (CFSs1), non-neutralized and heat-treated (CFSs2), pH neutralized, catalase-treated and non-heat-treated (CFSs3), or neutralized, catalase- and heat-treated (CFSs4) CFSs against 18 H. pylori strains (11 of which with antibiotic resistance) was evaluated. All GLB strains produced bacteriocin-like inhibitory substances (BLISs), the neutralized CFSs of two GLB strains inhibited >81% of test strains and those of four GLB strains were active against >71% of antibiotic resistant strains. Two H. pylori strains were BLIS resistant. The heating did not reduce the CFS activity. Briefly, all GLB strains evaluated produced heat-stable BLISs, although GLB and H. pylori strain susceptibility patterns exhibited differences. Bacteriocin-like inhibitory substance activity can be an advantage for the probiotic choice for H. pylori infection control. In this study, anti-Helicobacter pylori activity of seven Lactobacillus delbrueckii subsp. bulgaricus (GLB) strains was evaluated by four cell-free supernatant (CFS) types. The GLB strains produced heat-stable bacteriocin-like inhibitory substances (BLISs) with a strong anti-H. pylori activity and some neutralized, catalase- and heat-treated CFSs inhibited >83% of the test strains. Bacteriocin-like inhibitory substance production of GLB strains can render them valuable probiotics in the control of H. pylori infection. © 2017 The Society for Applied Microbiology.

Antifeedant, insecticidal and growth inhibitory activities of selected plant oils on black cutworm, Agrotis ipsilon (Hufnagel (Lepidoptera: Noctuidae

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Alagarmalai Jeyasankar

2012-05-01

Full Text Available Objective: To evaluate antifeedant, insecticidal and insect growth inhibitory activities of eucalyptus oil (Eucalyptus globules and gaultheria oil (Gaultheria procumbens L. against black cutworm, Agrotis ipsilon. Methods: Antifeedant, insecticidal and growth inhibitory activities of eucalyptus oil and gaultheria oil were tested against black cutworm, A. ipsilon. Results: Significant antifeedant activity was found in eucalyptus oil (96.24% where as the highest insecticidal activity was noticed in gaultheria oil (86.92%. Percentages of deformities were highest on gaultheria oil treated larvae and percentage of adult emergence was deteriorated also by gaultheria oil. Conclusions: These plants oil has potential to serve as an alternative eco-friendly control of insect pest.

The effect of curcumin in the ectonucleotidases and acetylcholinesterase activities in synaptosomes from the cerebral cortex of cigarette smoke-exposed rats.

Science.gov (United States)

Jaques, Jeandre Augusto Dos Santos; Rezer, João Felipe Peres; Gonçalves, Jamile Fabbrin; Spanevello, Rosélia Maria; Gutierres, Jessié Martins; Pimentel, Victor Câmera; Thomé, Gustavo Roberto; Morsch, Vera Maria; Schetinger, Maria Rosa Chitolina; Leal, Daniela Bitencourt Rosa

2011-12-01

With the evidence that curcumin may be a potent neuroprotective agent and that cigarette smoke is associated with a decline in the cognitive performance as our bases, we investigated the activities of Ecto-Nucleoside Triphosphate Diphosphohydrolase (NTPDase), 5'-nucleotidase and acetylcholinesterase (AChE) in cerebral cortex synaptosomes from cigarette smoke-exposed rats treated with curcumin (Cur). The experimental procedures entailed two sets of experiments. In the first set, the groups were vehicle, Cur 12·5, 25 and 50 mg·kg(-1) ; those in the second set were vehicle, smoke, smoke and Cur 12·5, 25 and 50 mg·kg(-1) . Curcumin prevented the increased NTPDase, 5'-nucleotidase and AChE activities caused by smoke exposure. We suggest that treatment with Cur was protective because the decrease of ATP and acetylcholine (ACh) concentrations is responsible for cognitive impairment, and both ATP and ACh have key roles in neurotransmission. Copyright © 2011 John Wiley & Sons, Ltd.

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

Science.gov (United States)

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

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. 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 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. PMID:24224169

LC-MS guided isolation of diterpenoids from Sapium insigne with α-glucosidase inhibitory activities.

Science.gov (United States)

Yan, De-Xiu; Geng, Chang-An; Yang, Tong-Hua; Huang, Xiao-Yan; Li, Tian-Ze; Gao, Zhen; Ma, Yun-Bao; Peng, Hua; Zhang, Xue-Mei; Chen, Ji-Jun

2018-04-08

Ten new (1-10) and ten known (11-20) diterpenoids involving ent-atisane, ent-seco-atisane, ent-kaurane and ent-seco-kaurane types were isolated from Sapium insigne under the guidance of LCMS-IT-TOF analyses. Their structures were characterized by extensive spectroscopic analyses (HRESIMS, UV, IR, 1D and 2D NMR). A putative biosynthetic pathway was proposed for ent-seco-atisane diterpenoids. Their inhibitory activities on α-glucosidase in vitro were tested for the first time. Compound 4 showed moderate inhibitory effect on α-glucosidase with an IC 50 value of 0.34 mM via a noncompetitive inhibition mechanism (K i  = 0.27 mM). The preliminary structure-activity relationships of the ent-atisane diterpenoids inhibiting α-glucosidase were discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

Determination of a-glucosidase inhibitory activity from selected Fabaceae plants.

Science.gov (United States)

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.

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

Energy Technology Data Exchange (ETDEWEB)

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)

Synthesis of 1-[{sup 11}c]methylpiperidin-4-yl propionate ([{sup 11}c]pmp) for in vivo measurements of acetylcholinesterase activity

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Snyder, Scott E. E-mail: snyderse@umich.edu; Tluczek, Louis; Jewett, Douglas M.; Nguyen, Thinh B.; Kuhl, David E.; Kilbourn, Michael R

1998-11-01

Synthesis of 1-[{sup 11}C]methylpiperidin-4-yl propionate ([{sup 11}C]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 [{sup 11}C]methyl trifluoromethanesulfonate at room temperature in N,N-dimethylformamide, followed by high performance liquid chromatography (HPLC) purification, provided [{sup 11}C]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. [{sup 11}C]PMP can thus be reliably prepared for routine clinical studies of acetylcholinesterase in human brain using positron emission tomography.

The Diversity of Cortical Inhibitory Synapses

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Yoshiyuki eKubota

2016-04-01

Full Text Available The most typical and well known inhibitory action in the cortical microcircuit is a strong inhibition on the target neuron by axo-somatic synapses. However, it has become clear that synaptic inhibition in the cortex is much more diverse and complicated. Firstly, at least ten or more inhibitory non-pyramidal cell subtypes engage in diverse inhibitory functions to produce the elaborate activity characteristic of the different cortical states. Each distinct non-pyramidal cell subtype has its own independent inhibitory function. Secondly, the inhibitory synapses innervate different neuronal domains, such as axons, spines, dendrites and soma, and their IPSP size is not uniform. Thus cortical inhibition is highly complex, with a wide variety of anatomical and physiological modes. Moreover, the functional significance of the various inhibitory synapse innervation styles and their unique structural dynamic behaviors differ from those of excitatory synapses. In this review, we summarize our current understanding of the inhibitory mechanisms of the cortical microcircuit.

Glutathione regulation-based dual-functional upconversion sensing-platform for acetylcholinesterase activity and cadmium ions.

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Fang, Aijin; Chen, Hongyu; Li, Haitao; Liu, Meiling; Zhang, Youyu; Yao, Shouzhuo

2017-01-15

A dual-functional platform for the sensing of acetylcholinesterase (AChE) activity and cadmium ions (Cd 2+ ) was developed based on the fluorescence resonance energy transfer (FRET) between NaYF 4 :Yb,Er upconversion nanoparticles (UCNPs) and gold nanoparticles (AuNPs) via glutathione regulation. The detection mechanism is based on the fact that AuNPs can quench the fluorescence of UCNPs. AChE catalyzes the hydrolysis of acetylthiocholine (ATC) into thiocholine which reacts with AuNPs by S-Au conjunction and results the aggregation of AuNPs and change in fluorescence of UCNPs. Therefore, the AChE activity can be detected through the changes of the color of solution and fluorescence recovery of UCNPs. However, the presence of glutathione (GSH) can protect AuNPs from aggregation and enlarge the inter-particle distance between AuNPs and UCNPs. When Cd 2+ is added into the stable mixture of AuNPs, GSH and AChE/ATC, Cd 2+ could interact with GSH to form a spherical shaped (GSH) 4 Cd complex, which decreases the free GSH on the surface of AuNPs to weaken the stability of AuNPs and lead to the easily aggregation of them in the system. The aggregated-AuNPs are released from the surface of UCNPs, which results in the fluorescence of UCNPs gradually recovered. Under the optimized conditions, the detection limits of AChE activity and Cd 2+ are estimated to be 0.015mU/mL and 0.2µM, respectively. The small molecules regulated dual-functional platform based on UCNPs/AuNPs is a simple, label-free method and can be applied for the turn-on fluorescence detection of AChE activity in human serum and Cd 2+ in real water samples. The present work demonstrates a general strategy for the design of small molecules regulated multifunctional platform and will be expanded for different areas in the future. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluation of the Stability of the Total Antioxidant Capacity, Polyphenol Contents, and Starch Hydrolase Inhibitory Activities of Kombucha Teas Using an In Vitro Model of Digestion

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Mindani I. Watawana

2015-01-01

Full Text Available The objective of this study was to evaluate and compare antioxidant and starch hydrolase inhibitory activity of three different types of Kombucha beverages prepared by three pellicles with different microbial compositions. The fermentation process was carried out for 7 days and the assessments of antioxidant and starch hydrolase inhibitory activities as well as tea phenolic compounds were carried out. These parameters were also evaluated after subjecting the final fermented samples to gastric and duodenal digestion in an in vitro digestion model. The pH had a statistically significant decrease during the period of fermentation. The total phenolics content and antioxidant activities had increased during the fermentation process as well as when subjected to digestion. The starch hydrolase inhibitory activities also increased in a similar manner during the different phases. The α-amylase and α-glucosidase inhibitory activities showed statistically significant increases (P<0.05 as the fermentation progressed, while an increase was observed after being subjected to pancreatic and duodenal digestion as well. All three types of tea showed a higher α-amylase inhibitory activity than α-glucosidase inhibitory activity.

Biotransformation of isoimperatorin and imperatorin by Glomerella cingulata and beta-secretase inhibitory activity.

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Marumoto, Shinsuke; Miyazawa, Mitsuo

2010-01-01

Biotransformation studies conducted on the furanocoumarins isoimperatorin (1) and imperatorin (3) have revealed that 1 was metabolized by Glomerella cingulata to give the corresponding reduced acid, 6,7-furano-5-prenyloxy hydrocoumaric acid (2), and 3 was transformed by G. cingulata to give the dealkylated metabolite, xanthotoxol (4) in high yields (83% and 81%), respectively. The structures of the new compound 2 have been established on the basis of spectral data. The metabolites 2 and 4 were tested for the beta-secretase (BACE1) inhibitory activity in vitro, and metabolite 2 slightly inhibited the beta-secretase activity with an IC(50) value of 185.6+/-6.8 microM. The metabolite 4 was less potent activity than compounds 1-3. In addition, methyl ester (2Me), methyl ether (2a) and methyl ester and ether (2aMe) of 2 were synthesized, and investigated for the ability to inhibit beta-secretase. Compound 2aMe exhibited the best beta-secretase inhibitory activity at the IC(50) value 16.2+/-1.2 microM and found to be the 2aMe showed competitive mode of inhibition against beta-secretase with K(i) value 11.3+/-2.8 microM. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Assessing joint toxicity of four organophosphate and carbamate insecticides in common carp (Cyprinus carpio) using acetylcholinesterase activity as an endpoint.

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Wang, Yanhua; Chen, Chen; Zhao, Xueping; Wang, Qiang; Qian, Yongzhong

2015-07-01

Mixtures of organophosphate (OP) and carbamate (CB) pesticides are commonly detected in freshwater ecosystems. These pesticides inhibit the activity of acetylcholinesterase (AChE) and have potential to interfere with behaviors that may be essential for the survival of species. Although the effects of individual anticholinesterase insecticides on aquatic species have been studied for decades, the neurotoxicity of mixtures is still poorly understood. In the present study, brain AChE inhibition in carp (Cyprinus carpio) exposed to a series of concentrations of the organophosphates (malathion and triazophos) as well as the carbamates (fenobucarb and carbosulfan) was measured. In equitoxic mixtures, the observed AChE activity inhibition of the malathion plus triazophos, and triazophos plus carbosulfan mixtures, was synergism. In equivalent concentration mixtures, the combination of malathion plus fenobucarb mixture conformed to synergism, while the observed AChE activity inhibition of the remaining pairings was less than additive. Single pesticide risk assessments are likely to underestimate the impacts of these insecticides on carps in aquatic environment where mixtures occur. Moreover, mixtures of pesticides that have been commonly reported in aquatic ecosystems may pose a more important challenge than previously anticipated. Copyright © 2014 Elsevier Inc. All rights reserved.

Hypotensive and Angiotensin-Converting Enzyme Inhibitory Activities of Eisenia fetida Extract in Spontaneously Hypertensive Rats

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Shumei Mao

2015-01-01

Full Text Available Objectives. This study aimed to investigate the antihypertensive effects of an Eisenia fetida extract (EFE and its possible mechanisms in spontaneously hypertensive rats (SHR rats. Methods. Sixteen-week-old SHR rats and Wistar-Kyoto rats (WKY rats were used in this study. Rats were, respectively, given EFE (EFE group, captopril (captopril group, or phosphate-buffered saline (PBS (normal control group and SHR group for 4 weeks. ACE inhibitory activity of EFE in vitro was determined. The systolic blood pressure (SBP and diastolic blood pressure (DBP were measured using a Rat Tail-Cuff Blood Pressure System. Levels of angiotensin II (Ang II, aldosterone (Ald, and 6-keto-prostaglandin F1 alpha (6-keto-PGF1α in plasma were determined by radioimmunoassay, and serum nitric oxide (NO concentration was measured by Griess reagent systems. Results. EFE had marked ACE inhibitory activity in vitro (IC50 = 2.5 mg/mL. After the 4-week drug management, SHR rats in EFE group and in captopril group had lower SBP and DBP, lower levels of Ang II and Ald, and higher levels of 6-keto-PGF1α and NO than the SHR rats in SHR group. Conclusion. These results indicate that EFE has hypotensive effects in SHR rats and its effects might be associated with its ACE inhibitory activity.

Development of Cholinesterase Inhibitors Using (a)-Lipoic Acid-benzyl Piperazine Hybrid Molecules

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Kim, Beomcheol; Lee, Seunghwan; Jang, Mi; Shon, Min Young; Park, Jeong Ho

2013-01-01

A series of hybrid molecules between (α)-lipoic acid (ALA) and benzyl piperazines were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibitory activities were evaluated. Even though the parent compounds did not show any inhibitory activity against cholinesterase (ChE), all hybrid molecules showed BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, ALA-1-(3-methylbenzyl)piperazine (15) was shown to be an effective inhibitor of both BuChE (IC 50 = 2.3 ± 0.7 μM) and AChE (IC 50 = 30.31 ± 0.64 μM). An inhibition kinetic study using compound 15 indicated a mixed inhibition type. Its binding affinity (K i ) value to BuChE is 2.91 ± 0.15 μM

Associations of Physical Activity, Sports Participation and Active Commuting on Mathematic Performance and Inhibitory Control in Adolescents.

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Domazet, Sidsel L; Tarp, Jakob; Huang, Tao; Gejl, Anne Kær; Andersen, Lars Bo; Froberg, Karsten; Bugge, Anna

2016-01-01

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 performance.

Associations of Physical Activity, Sports Participation and Active Commuting on Mathematic Performance and Inhibitory Control in Adolescents.

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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

Evaluation of enzymes inhibition activities of medicinal plant from Burkina Faso.

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Bangou, Mindiédiba Jean; Kiendrebeogo, Martin; Meda, Nâg-Tiero Roland; Coulibaly, Ahmed Yacouba; Compaoré, Moussa; Zeba, Boukaré; Millogo-Rasolodimby, Jeanne; Nacoulma, Odile Germaine

2011-01-15

The aim of the present study was to evaluate some enzymes inhibitory effects of 11 plant species belonging to 9 families from Burkina Faso. Methanolic extracts were used for their Glutathione-s-transferase (GST), Acetylcholinesterase (AChE), Carboxylesterase (CES) and Xanthine Oxidase (XO) inhibitory activities at final concentration of 100 microg mL(-1). The total phenolics, flavonoids and tannins were also determined spectrophotometrically using Folin-Ciocalteu, AlCl3 and ammonium citrate iron reagents, respectively. Among the 11 species tested, the best inhibitory percentages were found with Euphorbia hirta, Sclerocarya birrea and Scoparia dulcis (inhibition > 40%) followed by Annona senegalensis, Annona squamosa, Polygala arenaria and Ceratotheca sesamoides (inhibition > 25%). The best total phenolic and tannin contents were found with S. birrea with 56.10 mg GAE/100 mg extract and 47.75 mg TAE/100 mg extract, respectively. E hirta presented the higher total flavonoids (9.96 mg QE/100 mg extract). It's was found that Sclerocarya birrea has inhibited all enzymes at more than 30% and this activity is correlated to total tannins contents. Contrary to S. birrea, the enzymatic activities of E. hirta and S. dulcis are correlated to total flavonoids contents. Present findings suggest that the methanolic extracts of those plant species are potential inhibitors of GST, AChE, CES and XO and confirm their traditional uses in the treatment of mental disorders, gout, painful inflammations and cardiovascular diseases.

Novel N-allyl/propargyl tetrahydroquinolines: Synthesis via Three-component Cationic Imino Diels-Alder Reaction, Binding Prediction, and Evaluation as Cholinesterase Inhibitors.

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Rodríguez, Yeray A; Gutiérrez, Margarita; Ramírez, David; Alzate-Morales, Jans; Bernal, Cristian C; Güiza, Fausto M; Romero Bohórquez, Arnold R

2016-10-01

New N-allyl/propargyl 4-substituted 1,2,3,4-tetrahydroquinolines derivatives were efficiently synthesized using acid-catalyzed three components cationic imino Diels-Alder reaction (70-95%). All compounds were tested in vitro as dual acetylcholinesterase and butyryl-cholinesterase inhibitors and their potential binding modes, and affinity, were predicted by molecular docking and binding free energy calculations (∆G) respectively. The compound 4af (IC50 = 72 μm) presented the most effective inhibition against acetylcholinesterase despite its poor selectivity (SI = 2), while the best inhibitory activity on butyryl-cholinesterase was exhibited by compound 4ae (IC50 = 25.58 μm) with considerable selectivity (SI = 0.15). Molecular docking studies indicated that the most active compounds fit in the reported acetylcholinesterase and butyryl-cholinesterase active sites. Moreover, our computational data indicated a high correlation between the calculated ∆G and the experimental activity values in both targets. © 2016 The Authors Chemical Biology & Drug Design Published by John Wiley & Sons Ltd.

Changes in antioxidant status, protein concentration, acetylcholinesterase, (Na+,K+)-, and Mg2+ -ATPase activities in the brain of hyper- and hypothyroid adult rats.

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Carageorgiou, Haris; Pantos, Constantinos; Zarros, Apostolos; Mourouzis, Iordanis; Varonos, Dennis; Cokkinos, Dennis; Tsakiris, Stylianos

2005-06-01

It is a common knowledge that metabolic reactions increase in hyperthyroidism and decrease in hypothyroidism. The aim of this work was to investigate how the metabolic reactions could affect the total antioxidant status (TAS), protein concentration (PC) and the activities of acetylcholinesterase (AChE), (Na+,K+)-ATPase and Mg2+ -ATPase in the brain of hyper- and hypothyroid adult male rats. Hyperthyroidism was induced in rats by subcutaneous administration of thyroxine (25 microg/l00 g body weight) once daily for 14 days, while hypothyroidism was induced by oral administration of propylthiouracil (0.05%) for 21 days. TAS, PC, and enzyme activities were evaluated spectrophotometrically in the homogenated brain of each animal. TAS, PC, and Mg2+ -ATPase activity were found unaffected in hyperthyroidism, while AChE and Na+,K+ -ATPase activities were reduced by 25% (p activities were found to be increased (approx. 23-30%, p activity and PC were shown to be inhibited (approx. 23-30%, p activities may reflect the different metabolic effects of hyper- and hypothyroidism. Such changes of the enzyme activities may differentially modulate the brain intracellular Mg2+, neural excitability, as well as the uptake and release of biogenic amines.

Effect of adult onset hypothyroidism on behavioral parameters and acetylcholinesterase isoforms activity in specific brain regions of male mice.

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Vasilopoulou, Catherine G; Constantinou, Caterina; Giannakopoulou, Dimitra; Giompres, Panagiotis; Margarity, Marigoula

2016-10-01

Thyroid hormones (TH) are essential for normal development and function of mammalian central nervous system (CNS); TH dysregulation has been implicated in several cognitive and behavioral deficits related to dysfunctions of neurotransmitter systems. In the present study, we investigated the effects of adult onset hypothyroidism on the activity of acetylcholinesterase (AChE) and on related behavioral parameters. For this purpose we used adult male Balb/cJ mice that were divided randomly into euthyroid and hypothyroid animal groups. Animals were rendered hypothyroid through administration of 1% w/v KClO4 in their drinking water for 8weeks. At the end of the treatment, learning/memory procedures were examined through step-through passive avoidance task while fear/anxiety was assessed using elevated plus-maze (EPM) and open-field (OF) tests. AChE activity was determined colorimetrically in two different fractions, salt-soluble fraction (SS) (containing mainly the G1 isoform) and detergent-soluble fraction (DS) (containing mainly the G4 isoform) in cerebral cortex, cerebellum, midbrain, hippocampus and striatum. Our results indicate that adult onset hypothyroidism caused significant memory impairment and increased fear/anxiety. Moreover, the activity of both isoforms of AChE was reduced in all brain regions examined in a brain region- and isoform-specific manner. Copyright © 2016. Published by Elsevier Inc.

Acotiamide hydrochloride (Z-338), a new selective acetylcholinesterase inhibitor, enhances gastric motility without prolonging QT interval in dogs: comparison with cisapride, itopride, and mosapride.

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Matsunaga, Yugo; Tanaka, Takao; Yoshinaga, Koji; Ueki, Shigeru; Hori, Yuko; Eta, Runa; Kawabata, Yoshihiro; Yoshii, Kazuyoshi; Yoshida, Kenji; Matsumura, Toshihiro; Furuta, Shigeru; Takei, Mineo; Tack, Jan; Itoh, Zen

2011-03-01

Acotiamide hydrochloride (acotiamide; N-[2-[bis(1-methylethyl) amino]ethyl]-2-[(2-hydroxy-4,5-dimethoxybenzoyl) amino] thiazole-4-carboxamide monohydrochloride trihydrate, Z-338) has been reported to improve meal-related symptoms of functional dyspepsia in clinical studies. Here, we examined the gastroprokinetic effects of acotiamide and its antiacetylcholinesterase activity as a possible mechanism of action in conscious dogs. Acotiamide increased postprandial gastric motor activity in conscious dogs with chronically implanted force transducers and, like itopride, mosapride, and cisapride, exhibited gastroprokinetic activity in these dogs. Furthermore, acotiamide improved clonidine-induced hypomotility and delayed gastric emptying. Acotiamide-enhanced postprandial gastroduodenal motility was suppressed completely by pretreatment with atropine, a muscarinic receptor antagonist. In in vitro studies, acotiamide enhanced acetylcholine- but not carbachol-induced contractile responses of guinea pig gastric antrum strips. Moreover, like itopride and neostigmine, acotiamide inhibited recombinant human and canine stomach-derived acetylcholinesterase (AChE) activity in vitro. The mode of the AChE inhibitory action of acotiamide was selective and reversible. Unlike itopride or mosapride, acotiamide showed no affinity for dopamine D(2) or serotonin 5-HT(4) receptors. With regard to cardiovascular side effects, unlike cisapride, acotiamide did not affect myocardial monophasic action potential duration, QT interval, or corrected QT interval in anesthetized dogs. These results suggest that acotiamide stimulates gastric motility in vivo by inhibiting AChE activity without affecting QT interval. Acotiamide thus represents a beneficial new drug for the treatment of functional dyspepsia involving gastric motility dysfunction, with differences from other prokinetic agents.

Inhibitory Effect of Capparis spinosa Extract on Pancreatic Alpha-Amylase Activity

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Mostafa Selfayan

2016-04-01

Full Text Available Background Diabetes mellitus is a metabolic disorder characterized by high blood glucose level caused due to deficiency of insulin secretion or insulin function. The inhibition of carbohydrate hydrolyzing enzymes such as α-amylase can be an important strategy for decrease postprandial blood glucose level in patients with type II diabetes. Plants contains different chemical constituents with potential for inhibition of α-amylase and hence maybe used as therapeutic. Objectives The aim of the present study is to investigate the effect of the ethanolic extract of Capparis spinosa on pancreatic α-amylase activities to find out the relevance of the plant in controlling blood sugar. Materials and Methods In this experimental study, root and leaves of C. spinosa were tested for α-amylase inhibition. Different concentrations (1.56, 3.12, 6.25, 12.5 and 25 mg/mL of extracts were incubated with enzyme substrate solution and the spectrometric method used for measure enzyme activity. Also acarbose was used as the standard inhibitor. Results Both root and leaves extracts showed inhibition of α-amylase (root = 97.31% and leaves = 98.92%. The root and leaves extracts of C. spinosa exhibited appreciable α-amylase inhibitory activity with an IC50 values 5.93 mg/mL and 3.89 mg/mL respectively, when compared with acarbose (IC50 value 0.038 mg/mL. Conclusions This study supports that root and leaves extracts of C. spinosa exhibit considerable α-amylase inhibitory activities. These results could be useful for developing functional foods by combination of plant-based foods for treatment of diabetes mellitus.

Virtual Screening of Acetylcholinesterase Inhibitors Using the Lipinski’s Rule of Five and ZINC Databank

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Pablo Andrei Nogara

2015-01-01

Full Text Available Alzheimer’s disease (AD is a progressive and neurodegenerative pathology that can affect people over 65 years of age. It causes several complications, such as behavioral changes, language deficits, depression, and memory impairments. One of the methods used to treat AD is the increase of acetylcholine (ACh in the brain by using acetylcholinesterase inhibitors (AChEIs. In this study, we used the ZINC databank and the Lipinski’s rule of five to perform a virtual screening and a molecular docking (using Auto Dock Vina 1.1.1 aiming to select possible compounds that have quaternary ammonium atom able to inhibit acetylcholinesterase (AChE activity. The molecules were obtained by screening and further in vitro assays were performed to analyze the most potent inhibitors through the IC50 value and also to describe the interaction models between inhibitors and enzyme by molecular docking. The results showed that compound D inhibited AChE activity from different vertebrate sources and butyrylcholinesterase (BChE from Equus ferus (EfBChE, with IC50 ranging from 1.69 ± 0.46 to 5.64 ± 2.47 µM. Compound D interacted with the peripheral anionic subsite in both enzymes, blocking substrate entrance to the active site. In contrast, compound C had higher specificity as inhibitor of EfBChE. In conclusion, the screening was effective in finding inhibitors of AChE and BuChE from different organisms.

Enhancement of anti-cholinesterase activity of Zingiber cassumunar essential oil using a microemulsion technique.

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Okonogi, S; Chaiyana, W

2012-10-01

The aim of the present study was to enhance the cholinesterase inhibitory activity of Zingiber cassumunar (ZC) oil using a microemulsion (ME) technique. Pseudoternary phase diagrams of the oil, water, and surfactant/co-surfactant mixture were constructed using a water titration method. Effects of co-surfactant, surfactant/co-surfactant ratio, ionic strength, and pH were examined by means of the microemulsion region which existed in the phase diagrams. The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were tested by Ellman's colorimetric assay. It was found that ZC oil possesses inhibitory activity against not only AChE but also BChE. Formulation of ZC oil as ME revealed that alkyl chain length and number of hydroxyl groups of co-surfactant exhibited a remarkable effect on the pseudoternary phase diagram. Longer alkyl chains and more hydroxyl groups gave smaller regions of MEs. Ionic strength also affected the ME region. However, the phase behavior was hardly influenced by pH. The suitable ZC oil ME was composed of Triton X-114 in combination with propylene glycol. The anti-cholinesterase activity of this ME was much higher than that of native ZC oil. It exhibited twenty times and twenty five times higher inhibitory activity against AChE and BChE, respectively. ZC oil loaded ME is an attractive formulation for further characterization and an in vivo study in an animal model with Alzheimer's disease.

Natural sesquiterpen lactones as acetylcholinesterase inhibitors

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HOMA HAJIMEHDIPOOR

2014-06-01

Full Text Available Background and the purpose of the study: The amount of elder people who suffer from Alzheimer disease is continuously increasing every year. Cholinesterase inhibitors have shown to be effective in alleviating the symptoms of the disease, thus opening a field of research for these treatments. Herbal products, owning a reputation as effective agents in many biological studies are now drawing attention for inhibiting acetylcholinesterase, in other words, Alzheimer disease. In the present study, the ability of three sesquiterpene lactones from Inula oculus-christi and I. aucheriana to inhibit AChE has been evaluated through Ellman assay.Materials and Methods: Gaillardin and pulchellin C were obtained from I. oculus-christi and britannin from I. aucheriana by chromatographic methods. They were dissolved in methanol in concentration of 3 mg/mL and the AChEI activity of the compounds was determined by Ellman method using Acethylthiocholine iodide as the substrate and 5, 5′-dithiobis-2-nitrobenzoic acid as the reagent, in 96-well plates at 405 nm.Results: AChEI activity of the examined compounds was obtained as 67.0, 25.2 and 10.9% in concentration of 300 µg/L for gaillardin, britannin and pulchellin C, respectively.Conclusion: Among the three sesquiterpene lactones, gaillardin with 67% inhibition of AChE could be considered a good candidate for future Alzheimer studies.

Effects of reward and punishment on brain activations associated with inhibitory control in cigarette smokers.

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Luijten, Maartje; O'Connor, David A; Rossiter, Sarah; Franken, Ingmar H A; Hester, Robert

2013-11-01

Susceptibility to use of addictive substances may result, in part, from a greater preference for an immediate small reward relative to a larger delayed reward or relative insensitivity to punishment. This functional magnetic resonance imaging (fMRI) study examined the neural basis of inhibiting an immediately rewarding stimulus to obtain a larger delayed reward in smokers. We also investigated whether punishment could modulate inhibitory control. The Monetary Incentive Go/NoGo (MI-Go/NoGo) task was administered that provided three types of reward outcomes contingent upon inhibitory control performance over rewarding stimuli: inhibition failure was either followed by no monetary reward (neutral condition), a small monetary reward with immediate feedback (reward condition) or immediate monetary punishment (punishment condition). In the reward and punishment conditions, successful inhibitory control resulted in larger delayed rewards. Community sample of smokers in the Melbourne (Australia) area. Nineteen smokers were compared with 17 demographically matched non-smoking controls. Accuracy, reaction times and brain activation associated with the MI-Go/NoGo task. Smokers showed hyperactivation in the right insula (P rewarding stimulus to obtain a larger delayed reward, and during inhibition of neutral stimuli. Group differences in brain activity were not significant in the punishment condition in the right insula and dorsolateral prefrontal cortex, most probably as a result of increased activation in non-smoking controls. Compared with non-smokers, smokers showed increased neural activation when resisting immediately rewarding stimuli and may be less sensitive to punishment as a strategy to increase control over rewarding stimuli. © 2013 Society for the Study of Addiction.

College Binge Drinking Associated with Decreased Frontal Activation to Negative Emotional Distractors during Inhibitory Control

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Julia E. Cohen-Gilbert

2017-09-01

Full Text Available The transition to college is associated with an increase in heavy episodic alcohol use, or binge drinking, during a time when the prefrontal cortex and prefrontal-limbic circuitry continue to mature. Traits associated with this immaturity, including impulsivity in emotional contexts, may contribute to risky and heavy episodic alcohol consumption. The current study used blood oxygen level dependent (BOLD multiband functional magnetic resonance imaging (fMRI to assess brain activation during a task that required participants to ignore background images with positive, negative, or neutral emotional valence while performing an inhibitory control task (Go-NoGo. Subjects were 23 college freshmen (seven male, 18–20 years who engaged in a range of drinking behavior (past 3 months’ binge episodes range = 0–19, mean = 4.6, total drinks consumed range = 0–104, mean = 32.0. Brain activation on inhibitory trials (NoGo was contrasted between negative and neutral conditions and between positive and neutral conditions using non-parametric testing (5000 permutations and cluster-based thresholding (z = 2.3, p ≤ 0.05 corrected. Results showed that a higher recent incidence of binge drinking was significantly associated with decreased activation of dorsolateral prefrontal cortex (DLPFC, dorsomedial prefrontal cortex (DMPFC, and anterior cingulate cortex (ACC, brain regions strongly implicated in executive functioning, during negative relative to neutral inhibitory trials. No significant associations between binge drinking and brain activation were observed for positive relative to neutral images. While task performance was not significantly associated with binge drinking in this sample, subjects with heavier recent binge drinking showed decreased recruitment of executive control regions under negative versus neutral distractor conditions. These findings suggest that in young adults with heavier recent binge drinking, processing of negative emotional

Old and new acetylcholinesterase inhibitors for Alzheimer's disease.

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Galimberti, Daniela; Scarpini, Elio

2016-10-01

To date, pharmacological treatment of Alzheimer's disease (AD) includes Acetylcholinesterase Inhibitors (AChEIs) for mild-to-moderate AD, and memantine for moderate-to-severe AD. AChEIs reversibly inhibit acetylcholinesterase (AChE), thus increasing the availability of acetylcholine in cholinergic synapses, enhancing cholinergic transmission. These drugs provide symptomatic short-term benefits, without clearly counteracting the progression of the disease. On the wake of successful clinical trials which lead to the marketing of AChEIs donepezil, rivastigmine and galantamine, many compounds with AChEI properties have been developed and tested mainly in Phase I-II clinical trials in the last twenty years. Here, we review clinical trials initiated and interrupted, and those ongoing so far. Despite many clinical trials with novel AChEIs have been carried out after the registration of those currently used to treat mild to moderate AD, none so far has been successful in a Phase III trial and marketed. Alzheimer's disease is a complex multifactorial disorder, therefore therapy should likely address not only the cholinergic system but also additional neurotransmitters. Moreover, such treatments should be started in very mild phases of the disease, and preventive strategies addressed in elderly people.

Preliminary phytochemical screening and alpha-glucosidase inhibitory activity of Philippine taro (Colocasia esculenta (L.) Schott var. PSB-VG #9)

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Lebosada, Richemae Grace R.; Librando, Ivy L.

2017-01-01

The study was conducted to determine the anti-hyperglycemic property in terms of α-glucosidase inhibitory activity of the various parts (corm, leaf and petiole) of Colocasia esculenta (L.) Schott var. PSB-VG #9. Each of the plant parts were extracted with 95% ethanol and concentrated using a rotary evaporator at 40 °C. The crude extracts were screened for the presence of alkaloids, flavonoids, glycosides and saponins using Thin Layer Chromatography. The α-glucosidase inhibitory activity of the crude extracts (50 mg/L) were assayed spectrophotometrically using a microplate reader. The results of the phytochemical screening revealed the presence of alkaloids, flavonoids, and saponins in the leaf part while flavonoids and saponins were detected in the petiole and only saponins were present in the corm. The assay showed that the percentage α-glucosidase inhibition of the 50 mg/L ethanolic crude extract of the corm, leaves and petiole of C. esculenta are 68.03, 71.64 and 71.39%, respectively. Statistical analysis shows significant differences in the α-glucosidase inhibition among the various plant parts. It can be concluded that the ethanolic crude extracts of the different parts of C. esculenta (L.) Schott var. PSB-VG #9 exhibited inhibitory activity against α-glucosidase and the presence of phytochemicals like alkaloids, flavonoids and saponins may have contributed greatly to the inhibitory activity of the plant extract and can be further subjected for isolation of the therapeutically active compounds with antidiabetes potency.

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

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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

Aldose Reductase Inhibitory Activity of Compounds from  Zea mays L.

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Kim, Tae Hyeon; Kim, Jin Kyu; Kang, Young-Hee; Lee, Jae-Yong; Kang, Il Jun; Lim, Soon Sung

2013-01-01

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. PMID:23586057

Secoiridoids from the stem barks of Fraxinus rhynchophylla with pancreatic lipase inhibitory activity.

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Ahn, Jong Hoon; Shin, Eunjin; Liu, Qing; Kim, Seon Beom; Choi, Kyeong-Mi; Yoo, Hwan-Soo; Hwang, Bang Yeon; Lee, Mi Kyeong

2013-01-01

Pancreatic lipase digests dietary fats by hydrolysis, which is a key enzyme for lipid absorption. Therefore, reduction of fat absorption by the inhibition of pancreatic lipase is suggested to be a therapeutic strategy for obesity. From the EtOAc-soluble fraction of the stem barks of Fraxinus rhynchophylla (Oleaceae), four secoiridoids such as ligstroside (1), oleuropein (2), 2"-hydroxyoleuropein (3) and hydroxyframoside B (4) were isolated. The inhibitory activity of these compounds on pancreatic lipase was assessed using porcine pancreatic lipase as an in vitro assay system. Compound 4 showed the strongest inhibition on pancreatic lipase, which followed by compounds 1-3. In addition, compound 4 exerted inhibitory effect on pancreatic lipase in a mixed mechanism of competitive and noncompetitive manner. Taken together, F. rhynchophylla and its constituents might be beneficial to obesity.

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.

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

2009-04-28

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 an intriguing question whether this model could be used with erythrocyte AChE from other species in order to investigate kinetic interactions in the absence of annoying side reactions. Rhesus monkey, swine and guinea pig erythrocytes were a stable and highly reproducible enzyme source. Then, the model was applied to the reactivation of sarin- and paraoxon-inhibited AChE by obidoxime or HI 6 and it could be shown that the derived reactivation rate constants were in good agreement to previous results obtained from experiments with a static model. Hence, this dynamic model offers the possibility to investigate highly reproducible interactions between AChE, OP and oximes with human and animal AChE.

Colletotrichine A, a new sesquiterpenoid from Colletotrichum gloeosporioides GT-7, a fungal endophyte of Uncaria rhynchophylla.

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Chen, Xiao-Wei; Yang, Zhong-Duo; Sun, Jian-Hui; Song, Tong-Tong; Zhu, Bao-Ying; Zhao, Jun-Wen

2018-04-01

One new compound, Colletotrichine A (1), was produced by the fungal Colletotrichum gloeosporioides GT-7. The structure was established by 1D and 2D NMR spectra. Monoamine oxidase (MAO) and acetylcholinesterase (AChE) inhibitory activity of 1 was also evaluated. Compound 1 showed AChE-inhibiting activity with IC 50 value of 28 μg/mL.

Flavor Enhancer From Catfish (Clarias batrachus) Bekasam Powder and Angiotensin-I-Converting Enzyme (ACE) Inhibitory Activity in Various Dishes

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Lestari, Yanesti N.; Murwani, Retno; Agustini, Tri W.

2018-02-01

Flavor enhancer is characterized by high glutamic acid content and it can be obtained from fermented food such as Bekasam. Fermented food had inhibitory effect on Angiotensin-I-Converting Enzyme (ACE) activity which is advantageous for hypertension. However, such activity was not known to sustain in food system. The aim of this research was to study addition of flavour enhancer from Catfish Bekasam Powder (CBP) in various food systems and to determine the ACE inhibitory (ACEI) activity in the food system. Four food system consisted of carrot, champignon, and chicken meat dishes were boiled in water and added with CBP or MSG. Each food system was added with graded level of CBP (0%; 0.5%; 0.8%; 1.1%; and 1,4%) and for control monosodium glutamate (MSG) was used. ACEI activity in each food system and organoleptic test using multiple comparison differentiation on 15 semi-trained panellists were determined. The results showed that there were fluctuation of ACEI activity in the carrot, champignon, and chicken meat dishes (p=0.017; 0.043; and 0.032). The MSG containing dishes showed the lowest ACEI activity. Addition of graded level of CBP on carrot, champignon, and chicken meat dishes were directly proportional to glutamic acid content but inversely proportional to ACEI activity (pacid content but reduced ACE-inhibitory activity significantly (p<0.05). Comparing CBP to MSG addition in champignon dish revealed that increasing level of CBP increased the flavour preference of the panellists. On the contrary the higher the addition CBP in noodle and chicken meat dishes the worse were the flavour score (p<0.05). It can be concluded that the addition of CBP as flavour enhancer on various dishes can deliver better flavour and ACE-inhibitory activity than the addition of commercial MSG.

Structure-activity relationship of the inhibitory effects of flavonoids on nitric oxide production in RAW264.7 cells.

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Jiang, Wen-Jun; Daikonya, Akihiro; Ohkawara, Mitsuyoshi; Nemoto, Takashi; Noritake, Ryusuke; Takamiya, Tomoko; Kitanaka, Susumu; Iijima, Hiroshi

2017-01-15

We isolated flavonoids from herbal specimens from the Tibetan region (Sophora yunnanensis and Rhodiola sacra) that suppress nitric oxide (NO) production in macrophages stimulated by lipopolysaccharide and interferon-γ. The isolated flavonoids carry symmetric substitutions in the B ring (R 3' =R 5' ). We analyzed the quantitative structure-activity relationship of the inhibitory activity by comparative molecular field analysis (CoMFA) using this series of flavonoids. Use of flavonoids with symmetrical substitutions in the B ring made it simpler to align molecules because it was not necessary to consider a huge number of combinations due to the B-ring conformation. The CoMFA model, whose cross-validated q 2 value was 0.705, suggested the existence of a hydroxy group at the 5-position, the choice of the A/C-ring scaffold (chromane or chromene) and electrostatic field around the B ring are important for NO inhibitory activity. Flavonoids synthesized based on the CoMFA model exhibited significant inhibitory potential against NO production, validating the predictive capability of the CoMFA model. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biological Activities of Aerial Parts Extracts of Euphorbia characias

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Maria Barbara Pisano

2016-01-01

Full Text Available The aim of the present study was to evaluate antioxidant, antimicrobial, anti-HIV, and cholinesterase inhibitory activities of aqueous and alcoholic extracts from leaves, stems, and flowers of Euphorbia characias. The extracts showed a high antioxidant activity and were a good source of total polyphenols and flavonoids. Ethanolic extracts from leaves and flowers displayed the highest inhibitory activity against acetylcholinesterase and butyrylcholinesterase, showing potential properties against Alzheimer’s disease. Antimicrobial assay showed that leaves and flowers extracts were active against all Gram-positive bacteria tested. The ethanolic leaves extract appeared to have the strongest antibacterial activity against Bacillus cereus with MIC value of 312.5 μg/mL followed by Listeria monocytogenes and Staphylococcus aureus that also exhibited good sensitivity with MIC values of 1250 μg/mL. Moreover, all the extracts possessed anti-HIV activity. The ethanolic flower extract was the most potent inhibitor of HIV-1 RT DNA polymerase RNA-dependent and Ribonuclease H with IC50 values of 0.26 and 0.33 μg/mL, respectively. The LC-DAD metabolic profile showed that ethanolic leaves extract contains high levels of quercetin derivatives. This study suggests that Euphorbia characias extracts represent a good source of natural bioactive compounds which could be useful for pharmaceutical application as well as in food system for the prevention of the growth of food-borne bacteria and to extend the shelf-life of processed foods.

Inhibitory Effects of Respiration Inhibitors on Aflatoxin Production

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Shohei Sakuda

2014-03-01

Full Text Available Aflatoxin production inhibitors, which do not inhibit the growth of aflatoxigenic fungi, may be used to control aflatoxin without incurring a rapid spread of resistant strains. A respiration inhibitor that inhibits aflatoxin production was identified during a screening process for natural, aflatoxin-production inhibitors. This prompted us to evaluate respiration inhibitors as potential aflatoxin control agents. The inhibitory activities of four natural inhibitors, seven synthetic miticides, and nine synthetic fungicides were evaluated on aflatoxin production in Aspergillus parasiticus. All of the natural inhibitors (rotenone, siccanin, aptenin A5, and antimycin A inhibited fungal aflatoxin production with IC50 values around 10 µM. Among the synthetic miticides, pyridaben, fluacrypyrim, and tolfenpyrad exhibited strong inhibitory activities with IC50 values less than 0.2 µM, whereas cyflumetofen did not show significant inhibitory activity. Of the synthetic fungicides, boscalid, pyribencarb, azoxystrobin, pyraclostrobin, and kresoxim-methyl demonstrated strong inhibitory activities, with IC50 values less than 0.5 µM. Fungal growth was not significantly affected by any of the inhibitors tested at concentrations used. There was no correlation observed between the targets of respiration inhibitors (complexes I, II, and III and their IC50 values for aflatoxin-production inhibitory activity. This study suggests that respiration inhibitors, including commonly used pesticides, are useful for aflatoxin control.

Inhibitory Effects of Respiration Inhibitors on Aflatoxin Production

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Sakuda, Shohei; Prabowo, Diyan Febri; Takagi, Keiko; Shiomi, Kazuro; Mori, Mihoko; Ōmura, Satoshi; Nagasawa, Hiromichi

2014-01-01

Aflatoxin production inhibitors, which do not inhibit the growth of aflatoxigenic fungi, may be used to control aflatoxin without incurring a rapid spread of resistant strains. A respiration inhibitor that inhibits aflatoxin production was identified during a screening process for natural, aflatoxin-production inhibitors. This prompted us to evaluate respiration inhibitors as potential aflatoxin control agents. The inhibitory activities of four natural inhibitors, seven synthetic miticides, and nine synthetic fungicides were evaluated on aflatoxin production in Aspergillus parasiticus. All of the natural inhibitors (rotenone, siccanin, aptenin A5, and antimycin A) inhibited fungal aflatoxin production with IC50 values around 10 µM. Among the synthetic miticides, pyridaben, fluacrypyrim, and tolfenpyrad exhibited strong inhibitory activities with IC50 values less than 0.2 µM, whereas cyflumetofen did not show significant inhibitory activity. Of the synthetic fungicides, boscalid, pyribencarb, azoxystrobin, pyraclostrobin, and kresoxim-methyl demonstrated strong inhibitory activities, with IC50 values less than 0.5 µM. Fungal growth was not significantly affected by any of the inhibitors tested at concentrations used. There was no correlation observed between the targets of respiration inhibitors (complexes I, II, and III) and their IC50 values for aflatoxin-production inhibitory activity. This study suggests that respiration inhibitors, including commonly used pesticides, are useful for aflatoxin control. PMID:24674936

Hypothyroidism Enhanced Ectonucleotidases and Acetylcholinesterase Activities in Rat Synaptosomes can be Prevented by the Naturally Occurring Polyphenol Quercetin.

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Baldissarelli, Jucimara; Santi, Adriana; Schmatz, Roberta; Abdalla, Fátima Husein; Cardoso, Andréia Machado; Martins, Caroline Curry; Dias, Glaecir R Mundstock; Calgaroto, Nicéia Spanholi; Pelinson, Luana Paula; Reichert, Karine Paula; Loro, Vania Lucia; Morsch, Vera Maria Melchiors; Schetinger, Maria Rosa Chitolina

2017-01-01

Thyroid hormones have an influence on the functioning of the central nervous system. Furthermore, the cholinergic and purinergic systems also are extensively involved in brain function. In this context, quercetin is a polyphenol with antioxidant and neuroprotective properties. This study investigated the effects of (MMI)-induced hypothyroidism on the NTPDase, 5'-nucleotidase, adenosine deaminase (ADA), and acetylcholinesterase (AChE) activities in synaptosomes of rats and whether the quercetin can prevent it. MMI at a concentration of 20 mg/100 mL was administered for 90 days in the drinking water. The animals were divided into six groups: control/water (CT/W), control/quercetin 10 mg/kg, control/quercetin 25 mg/kg, methimazole/water (MMI/W), methimazole/quercetin 10 mg/kg (MMI/Q10), and methimazole/quercetin 25 mg/kg (MMI/Q25). On the 30th day, hormonal dosing was performed to confirm hypothyroidism, and the animals were subsequently treated with 10 or 25 mg/kg quercetin for 60 days. NTPDase activity was not altered in the MMI/W group. However, treatment with quercetin decreased ATP and ADP hydrolysis in the MMI/Q10 and MMI/Q25 groups. 5'-nucleotidase activity increased in the MMI/W group, but treatments with 10 or 25 mg/kg quercetin decreased 5'-nucleotidase activity. ADA activity decreased in the CT/25 and MMI/Q25 groups. Furthermore, AChE activity was reduced in all groups with hypothyroidism. In vitro tests also demonstrated that quercetin per se decreased NTPDase, 5'-nucleotidase, and AChE activities. This study demonstrated changes in the 5'-nucleotidase and AChE activities indicating that purinergic and cholinergic neurotransmission are altered in this condition. In addition, quercetin can alter these parameters and may be a promising natural compound with important neuroprotective actions in hypothyroidism.

Do piperacillin/tazobactam and other antibiotics with inhibitory activity against Clostridium difficile reduce the risk for acquisition of C. difficile colonization?

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Kundrapu, Sirisha; Sunkesula, Venkata C K; Jury, Lucy A; Cadnum, Jennifer L; Nerandzic, Michelle M; Musuuza, Jackson S; Sethi, Ajay K; Donskey, Curtis J

2016-04-18

Systemic antibiotics vary widely in in vitro activity against Clostridium difficile. Some agents with activity against C. difficile (e.g., piperacillin/tazobactam) inhibit establishment of colonization in mice. We tested the hypothesis that piperacillin/tazobactam and other agents with activity against C. difficile achieve sufficient concentrations in the intestinal tract to inhibit colonization in patients. Point-prevalence culture surveys were conducted to compare the frequency of asymptomatic rectal carriage of toxigenic C. difficile among patients receiving piperacillin/tazobactam or other inhibitory antibiotics (e.g. ampicillin, linezolid, carbapenems) versus antibiotics lacking activity against C. difficile (e.g., cephalosporins, ciprofloxacin). For a subset of patients, in vitro inhibition of C. difficile (defined as a reduction in concentration after inoculation of vegetative C. difficile into fresh stool suspensions) was compared among antibiotic treatment groups. Of 250 patients, 32 (13 %) were asymptomatic carriers of C. difficile. In comparison to patients receiving non-inhibitory antibiotics or prior antibiotics within 90 days, patients currently receiving piperacillin/tazobactam were less likely to be asymptomatic carriers (1/36, 3 versus 7/36, 19 and 15/69, 22 %, respectively; P = 0.024) and more likely to have fecal suspensions with in vitro inhibitory activity against C. difficile (20/28, 71 versus 3/11, 27 and 4/26, 15 %; P = 0.03). Patients receiving other inhibitory antibiotics were not less likely to be asymptomatic carriers than those receiving non-inhibitory antibiotics. Our findings suggest that piperacillin/tazobactam achieves sufficient concentrations in the intestinal tract to inhibit C. difficile colonization during therapy.

Curcumin and its demethoxy derivatives possess p300 HAT inhibitory activity and suppress hypertrophic responses in cardiomyocytes

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Yoichi Sunagawa

2018-04-01

Full Text Available The natural compound, curcumin (CUR, possesses several pharmacological properties, including p300-specific histone acetyltransferase (HAT inhibitory activity. In our previous study, we demonstrated that CUR could prevent the development of cardiac hypertrophy by inhibiting p300-HAT activity. Other major curcuminoids isolated from Curcuma longa including demethoxycurcumin (DMC and bisdemethoxycurcumin (BDMC are structural analogs of CUR. In present study, we first confirmed the effect of these three curcuminoid analogs on p300-HAT activity and cardiomyocyte hypertrophy.Our results showed that DMC and BDMC inhibited p300-HAT activity and cardiomyocyte hypertrophy to almost the same extent as CUR. As the three compounds have structural differences in methoxy groups at the 3-position of their phenol rings, our results suggest that these methoxy groups are not involved in the inhibitory effects on p300-HAT activity and cardiac hypertrophy. These findings provide useful insights into the structure–activity relationship and biological activity of curcuminoids for p300-HAT activity and cardiomyocyte hypertrophy. Keywords: Curcumin, Demethoxycurcumin, Bisdemethoxycurcumin, p300, Cardiomyocyte hypertrophy

Inhibitory effect of mTOR activator MHY1485 on autophagy: suppression of lysosomal fusion.

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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

A Support Vector Machine Classification Model for Benzo[c]phenathridine Analogues with Topoisomerase-I Inhibitory Activity

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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.

[Study on the inhibitory activity, in vitro, of baicalein and baicalin against skin fungi and bacteria].

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Yang, D; Hu, H; Huang, S; Chaumont, J P; Millet, J

2000-05-01

In this paper, we concentrated in examining, in vitro, the antiseptic activity of the baicalein and baicalin upon the seventeen pathogenic skin fungal and sixteen skin bacterial strains, these two flavonic compounds were known principally as the biosubstances of a traditional Chinese medicinal plant: Scutellaria baicalensis. In agar media, the baicalein possessed potent specific activity against the pathogenic yeasts with MICs of 70-100 micrograms/ml; But in the same condition, no inhibitory effect was observed upon dermatophytes and filamentous imperfect fungi for baicalein, and upon all used strains for baicalin. According to the antibacterial test of baicalein, a high efficacy was achieved against certain causative specie of axillary and foot's odour such as Micrococcus sedentarius, Staphylococcus epidermidis, S. hominis and C. xerosis with a MICs inferior to 250 micrograms/ml. The good inhibitory activity of baicalein could be linked to the group hydroxyl (-OH) in position seven of the molecule.

Development of Cholinesterase Inhibitors Using (a)-Lipoic Acid-benzyl Piperazine Hybrid Molecules

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Kim, Beomcheol; Lee, Seunghwan; Jang, Mi; Shon, Min Young; Park, Jeong Ho [Hanbat National Univ., Daejeon (Korea, Republic of)

2013-11-15

A series of hybrid molecules between (α)-lipoic acid (ALA) and benzyl piperazines were synthesized and their in vitro cholinesterase [acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)] inhibitory activities were evaluated. Even though the parent compounds did not show any inhibitory activity against cholinesterase (ChE), all hybrid molecules showed BuChE inhibitory activity. Some hybrid compounds also displayed AChE inhibitory activity. Specifically, ALA-1-(3-methylbenzyl)piperazine (15) was shown to be an effective inhibitor of both BuChE (IC{sub 50} = 2.3 ± 0.7 μM) and AChE (IC{sub 50} = 30.31 ± 0.64 μM). An inhibition kinetic study using compound 15 indicated a mixed inhibition type. Its binding affinity (K{sub i}) value to BuChE is 2.91 ± 0.15 μM.

Nanocapsular Dispersion of Cinnamaldehyde for Enhanced Inhibitory Activity against Aflatoxin Production by Aspergillus flavus

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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.

Associations of Physical Activity, Sports Participation and Active Commuting on Mathematic Performance and Inhibitory Control in Adolescents

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Huang, Tao; Gejl, Anne Kær; Froberg, Karsten

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 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. 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 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. Conclusions 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

Unmasking tandem site interaction in human acetylcholinesterase. Substrate activation with a cationic acetanilide substrate.

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Johnson, Joseph L; Cusack, Bernadette; Davies, Matthew P; Fauq, Abdul; Rosenberry, Terrone L

2003-05-13

Acetylcholinesterase (AChE) contains a narrow and deep active site gorge with two sites of ligand binding, an acylation site (or A-site) at the base of the gorge, and a peripheral site (or P-site) near the gorge entrance. The P-site contributes to catalytic efficiency by transiently binding substrates on their way to the acylation site, where a short-lived acyl enzyme intermediate is produced. A conformational interaction between the A- and P-sites has recently been found to modulate ligand affinities. We now demonstrate that this interaction is of functional importance by showing that the acetylation rate constant of a substrate bound to the A-site is increased by a factor a when a second molecule of substrate binds to the P-site. This demonstration became feasible through the introduction of a new acetanilide substrate analogue of acetylcholine, 3-(acetamido)-N,N,N-trimethylanilinium (ATMA), for which a = 4. This substrate has a low acetylation rate constant and equilibrates with the catalytic site, allowing a tractable algebraic solution to the rate equation for substrate hydrolysis. ATMA affinities for the A- and P-sites deduced from the kinetic analysis were confirmed by fluorescence titration with thioflavin T as a reporter ligand. Values of a >1 give rise to a hydrolysis profile called substrate activation, and the AChE site-specific mutant W86F, and to a lesser extent wild-type human AChE itself, showed substrate activation with acetylthiocholine as the substrate. Substrate activation was incorporated into a previous catalytic scheme for AChE in which a bound P-site ligand can also block product dissociation from the A-site, and two additional features of the AChE catalytic pathway were revealed. First, the ability of a bound P-site ligand to increase the substrate acetylation rate constant varied with the structure of the ligand: thioflavin T accelerated ATMA acetylation by a factor a(2) of 1.3, while propidium failed to accelerate. Second, catalytic rate

Introducing Dynamic Combinatorial Chemistry: Probing the Substrate Selectivity of Acetylcholinesterase

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Angelin, Marcus; Larsson, Rikard; Vongvilai, Pornrapee; Ramstrom, Olof

2010-01-01

In this laboratory experiment, college students are introduced to dynamic combinatorial chemistry (DCC) and apply it to determine the substrate selectivity of acetylcholinesterase (AChE). Initially, the students construct a chemical library of dynamically interchanging thioesters and thiols. Then, AChE is added and allowed to select and hydrolyze…

Angiotensin-converting enzyme-inhibitory activity in protein hydrolysates from normal and anthracnose disease-damaged Phaseolus vulgaris seeds.

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Hernández-Álvarez, Alan Javier; Carrasco-Castilla, Janet; Dávila-Ortiz, Gloria; Alaiz, Manuel; Girón-Calle, Julio; Vioque-Peña, Javier; Jacinto-Hernández, Carmen; Jiménez-Martínez, Cristian

2013-03-15

Bean seeds are an inexpensive source of protein. Anthracnose disease caused by the fungus Colletotrichum lindemuthianum results in serious losses in common bean (Phaseolus vulgaris L.) crops worldwide, affecting any above-ground plant part, and protein dysfunction, inducing the synthesis of proteins that allow plants to improve their stress tolerance. The aim of this study was to evaluate the use of beans damaged by anthracnose disease as a source of peptides with angiotensin-converting enzyme (ACE-I)-inhibitory activity. Protein concentrates from beans spoiled by anthracnose disease and from regular beans as controls were prepared by alkaline extraction and precipitation at isolelectric pH and hydrolysed using Alcalase 2.4 L. The hydrolysates from spoiled beans had ACE-I-inhibitory activity (IC(50) 0.0191 mg protein mL(-1)) and were very similar to those from control beans in terms of ACE-I inhibition, peptide electrophoretic profile and kinetics of hydrolysis. Thus preparation of hydrolysates using beans affected by anthracnose disease would allow for revalorisation of this otherwise wasted product. The present results suggest the use of spoiled bean seeds, e.g. anthracnose-damaged beans, as an alternative for the isolation of ACE-I-inhibitory peptides to be further introduced as active ingredients in functional foods. © 2012 Society of Chemical Industry.

Inhibitory Activity of Artemisia spicigera Essential Oil Against Fungal Species Isolated From Minced Meat

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Ghajarbeygi

2015-11-01

Full Text Available Background Meat is an important source of several nutrients. The capability top of fresh meat to rot, causing the group of studies food science, biological and chemical stability meat consideration. Objectives This study was conducted to examine the inhibitory effect of Artemisias spicigera essential oil against fungal species isolated from minced meat. Materials and Methods Two types of media dichloran 18% glycerol (DG18 agar and dichloran rosebengal chloramphenicol (DRBC agar were selected for the mycological analysis of the minced meat samples. To evaluate the antifungal activity of essential oils, the microdilution broth method based on the CLSI (M27A guideline was used. Results Artemisias spicigera essential oil has an inhibitory effect on the growth of fungi found in samples of minced meat. Aspergillus, Penicillium and Cladosporium were the most common genera on both medium types. Average Minimum Inhibitory Concentration 50 = 1.88 µL/mL and MIC90 = 2 µL/mL were reported. The genus of Mucor with MIC = 1.0 µL/mL was the most sensitive and Aspergilus versicolor was the most resistant species to the essential oil with MIC = 4 µL/mL. Conclusions The results of the present study show a favorable inhibitory effect of Artemisias spicigera essential oil on fungal growth, especially Aspergillus species. According to the results, antifungal components of Artemisias spicigera in different forms are used to prevent fungal pollution.

Biologically active compounds from cyanobacteria extracts: in vivo and in vitro aspects

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Luciana R. Carvalho

2013-05-01

Full Text Available An investigation was directed towards the antiacetylcholinesterase activity of the acid aqueous and methanolic extracts of five cyanobacterial taxa, which encompasses an enzymatic inhibition essay and the evaluation of the physiological responses of mice to cyanobacterial extracts along with toxicological observations. The strains Calothrix sp. CCIBt 3320, Tolypothrix sp. CCIBt 3321, Phormidium cf. amoenum CCIBt 3412, Phormidium sp. CCIBt 3265, and Geitlerinema splendidum CCIBt 3223 were from the São Paulo Botanical Institute Cyanobacterial Culture Collection and all of them showed inhibitory effect on acetylcholinesterase activity (in vitro and caused systemic effects similar to those described for anticholinesterase drugs (in vivo. With the exception of G. splendidum and Tolypothrix sp. strains, all extracts produced reversible antiacetylcolinesterase effects in mice. Complementary histopathological studies were carried out on tissues from animals administered with Phormidium sp. and P. cf. amoenum.

Biologically active compounds from cyanobacteria extracts: in vivo and in vitro aspects

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Luciana R. Carvalho

2013-06-01

Full Text Available An investigation was directed towards the antiacetylcholinesterase activity of the acid aqueous and methanolic extracts of five cyanobacterial taxa, which encompasses an enzymatic inhibition essay and the evaluation of the physiological responses of mice to cyanobacterial extracts along with toxicological observations. The strains Calothrix sp. CCIBt 3320, Tolypothrix sp. CCIBt 3321, Phormidium cf. amoenum CCIBt 3412, Phormidium sp. CCIBt 3265, and Geitlerinema splendidum CCIBt 3223 were from the São Paulo Botanical Institute Cyanobacterial Culture Collection and all of them showed inhibitory effect on acetylcholinesterase activity (in vitro and caused systemic effects similar to those described for anticholinesterase drugs (in vivo. With the exception of G. splendidum and Tolypothrix sp. strains, all extracts produced reversible antiacetylcolinesterase effects in mice. Complementary histopathological studies were carried out on tissues from animals administered with Phormidium sp. and P. cf. amoenum.

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

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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.

Evaluation of antioxidant potential, enzyme inhibition activity and phenolic profile of Lathyrus cicera and Lathyrus digitatus: Potential sources of bioactive compounds for the food industry.

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Llorent-Martínez, E J; Ortega-Barrales, P; Zengin, G; Mocan, A; Simirgiotis, M J; Ceylan, R; Uysal, S; Aktumsek, A

2017-09-01

The genus Lathyrus has great importance in terms of food and agricultural areas. In this study, the in vitro antioxidant activity (phosphomolybdenum, DPPH, ABTS, FRAP, CUPRAC and metal chelating) and enzyme inhibitory activity evaluation (acetylcholinesterase, butyrylcholinesterase, α-amylase and α-glucosidase) of L. cicera and L. digitatus were investigated, as well as their phytochemical profiles. The screening of the main phytochemical compounds in aerial parts of L. cicera and L. digitatus was carried out by high-performance liquid chromatography with electrospray ionization mass spectrometric detection (HPLC-ESI-MS n ), observing that flavonoids represent the highest percentage of identified compounds, with abundance of tri- and tetra-glycosilated flavonoids, including acylated ones, especially in L. cicera. Generally, L. digitatus exhibited stronger antioxidant and enzyme inhibitory activities in correlation with its higher level of phenolics. The high number of phenolic compounds and the results of the antioxidant and enzyme assays suggest that these plants may be further used as sources of bioactive compounds, and for the preparation of new nutraceuticals. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vitro inhibitory activity of essential oil vapors against Ascosphaera apis.

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Kloucek, Pavel; Smid, Jakub; Flesar, Jaroslav; Havlik, Jaroslav; Titera, Dalibor; Rada, Vojtech; Drabek, Ondrej; Kokoska, Ladislav

2012-02-01

This work evaluates the in vitro inhibitory activity of 70 essential oils (EOs) in the vapor phase for the control of Chalkbrood disease caused by Ascosphaera apis Maassen ex Claussen (Olive et Spiltoir). Two wild strains isolated from infected honey bee colonies together with one standard collection strain were tested by the microatmosphere method. From 70 EOs, 39 exhibited an antifungal effect against A. apis standard and wild strains. The greatest antifungal action was observed for EO vapors from Armoracia rusticana, followed by Thymus vulgaris, Cymbopogon flexosus, Origanum vulgare and Allium sativum. An investigation of chemical composition by GC-MS revealed, that the most active EOs contained allyl isothiocyanate, citral, carvacrol and diallyl sulfides as the main constituents. The chemical composition plays a key role, as activities of different EOs from the same botanical species were different according to their composition.

Identification of novel 2-benzoxazolinone derivatives with specific inhibitory activity against the HIV-1 nucleocapsid protein.