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P1‐085: IN SILICO STUDY OF PHYTOCONSTITUENTS FROM SELECTED TRADITIONAL SPICES AS POTENTIAL INHIBITORS OF β‐SITE AMYLOID PRECURSOR PROTEIN CLEAVING ENZYME (BACE1)
Author(s) -
Chowdhury Suman,
Kumar Suresh
Publication year - 2018
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2018.06.087
Subject(s) - in silico , amyloid precursor protein , enzyme , dock , chemistry , docking (animal) , peptide , biochemistry , active site , p3 peptide , ellagic acid , stereochemistry , alzheimer's disease , gene , antioxidant , medicine , disease , pathology , polyphenol , nursing
was administered i.c.v. on the 15 day. Memory was evaluated by novel object recognition task and Y-maze test. In the Ab induced memory impairment model, the effect on mitochondrial dysfunction, inflammation (TNF-a and IL-6), acetylcholinesterase (AChE) and b-secretase activities were evaluated in the brain tissue homogenates. The effect on neuronal degeneration in the hippocampus and prefrontal cortex was evaluated by H&E staining. In the OKA induced neurotoxicity model, antioxidant potential and effect on pro-inflammatory cytokines was evaluated. Results: Scopoletin significantly reversed the memory impairment in the behavioural tests. Scopoletin attenuated mitochondrial-oxidative damage. TNF-a and IL-6 levels were significantly increased after administration of the respective inducing agents. Scopoletin treatment significantly mitigated this effect. Malondialdehyde level was significantly reduced and the levels of GSH, SOD and catalase were significantly increased after scopoletin administration. Significant AChE inhibitory (AChEi) activity and down regulation of bsecretase was observed after scopoletin treatment as compared to disease control. Scopoletin treatment significantly reduced neuronal degeneration in hippocampus and prefrontal cortex. Conclusions: Scopoletin showed promising antioxidant, anti-inflammatory and AChEi activity. It significantly inhibited amyloidogenesis, neuronal degeneration, mitochondrial dysfunction, and memory impairment. Scopoletin may be a potential candidate for AD therapy as it targets multi facets of the disease.