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ORIGINAL ARTICLE
Year : 2017  |  Volume : 13  |  Issue : 51  |  Page : 437-445

Antioxidant and cholinesterase inhibitory activities of ethyl acetate extract of Terminalia chebula: Cell-free In vitro and In silico studies


1 Centre for Pheromone Technology, Department of Animal Science, School of Life Science, Bharathidasan University; National Center for Alternatives to Animal Experiments, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India
2 Centre for Pheromone Technology, Department of Animal Science, School of Life Science, Bharathidasan University, Tiruchirappalli; Department of Nanoscience and Technology, Alagappa University, Karaikudi, Tamil Nadu, India
3 Department of Biochemistry, Molecular Gerontology Laboratory, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India
4 National Center for Alternatives to Animal Experiments, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India; Department of Food Science and Nutrition, College of Food Science and Agriculture, King Saud University, Riyadh, Saudi Arabia

Correspondence Address:
Archunan Govindaraju
Department of Animal Science, Centre for Pheromone Technology, School of Life Sciences, Bharathidasan University, Tiruchirappalli - 620 024, Tamil Nadu
India
Suganthy Natarajan
Department of Nanoscience and Technology, Alagappa University, Karaikudi - 630 003, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/pm.pm_57_17

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Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder clinically characterized by memory loss and impaired cognitive function. Cholinergic enzyme deficiency and oxidative stress are the two major factors implicated in the pathogenesis of AD. The symptomatic treatment, as of now, is the use of cholinesterase inhibitors toward cholinergic “downturn.” Therefore, there is a search for compounds that will be useful in focused therapies. There has been suggestion that Terminalia chebula fruit would be a potential source. Objective: To assess the anticholinesterase and antioxidant activities of T. chebula fruit which is widely practiced in the Ayurvedic medicines for memory enhancement. Materials and Methods: Ethyl acetate extract of T. chebula fruit (TCEA) was subjected to phytochemical investigation of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities and cell-free antioxidant activity. TCEA was further subjected to gas chromatography-mass spectrum (GC-MS) analysis. The bioactive compounds were analyzed for molecular docking with AChE and BuChE proteins. Results: TCEA exhibited potent AChE and BuChE inhibitory activities comparable to the standard drug donepezil. In vitro cell-free antioxidant assays demonstrated that TCEA possesses excellent free radical scavenging activity, reducing power, and potent metal-chelating activity. Total polyphenolic content of TCEA was 596.75 ± 0.35 μg gallic acid equivalents/mg of extract, which correlates with the antioxidant activity of TCEA. Molecular docking of compounds expounded in GC-MS analysis for AChE and BuChE enzyme activities revealed that methyl N-(N-benzyloxycarbonyl-beta-l-aspartyl)-beta-d-glucosaminide as the most potent compound with good predicted activities. Conclusion: Overall, the results revealed that the bioactive molecule methyl N-(N-benzyloxycarbonyl-beta-l-aspartyl)-beta-d-glucosaminide present in TCEA is a potential depressant for the treatment of AD and related neurodegenerative disorders. Abbreviations used: AD: Alzheimer's disease; TCEA: Ethyl acetate extract of Terminalia chebula; GC-MS: Gas chromatography-mass spectrum; ROS: Reactive oxygen species; RNS: Reactive nitrogen species; AChE: Acetylcholinesterase; BuChE: Butyrylcholinesterase; NFT: Neurofibrillary tangles; Aβ : β -amyloid; NSAIDS: Nonsteroidal anti-inflammatory drugs; FDA: Food and Drug Administration; RT: Room temperature; HCl: Hydrochloric acid; ATCI: Acetylthiocholine iodide; BTCI: Butyrylthiocholine iodide; BHT: Butylated hydroxytoluene; DPPH: 2,2-diphenyl-1-picrylhydrazyl; TCA: Trichloroacetic acid; GAE: Gallic acid equivalent; NICT: National Institute of Information and Communications Technology; 3D: Three-dimensional; PDB: Protein data bank; OPLS: Optimized potentials for liquid simulations; XP: Extra precision; SD: Standard deviation; ANOVA: Analysis of variance; EDTA: Ethylenediaminetetraacetic acid.


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