A Virtual Study on the Multitarget Potential Efficacy of the Ligands, Alpha Asarone and Glabridin, in Ameliorating Behavioural Deficits due to Neurodegeneration of Hippocampus Induced by Chronic Restraint Stress

Abstract

Life span of human, a gradually increase can occur with change in diet and life style which play an important role in delaying or even block the progression of age related degenerative problems like dementia, Alzheimer’s which decrease the cognitive function mainly learning and memory. The objective of the study was to find the multitarget potential efficacy of the ligands, Alpha asarone and Glabridin, in ameliorating behavioral deficits due to hippocampal damaged neurodegenerative condition induced by chronic restraint stress. Hence in the current study we analyzed polypharmacological effect of the two natural compounds on the Mitogen activated protein kinases (MAPK’s) families which are mainly involved in neurodegenaration by molecular docking using iGEMDOCK software, the drug likeliness and their absorption, digestion metabolic and toxicity profile were analyzed by DruLiTo and admetSAR software. With the results of molecular docking the two natural compounds were selected and taken for experimental study.Experimental Groups received chronic restraint stress 6hrs/day for 21days. Behavioural performance, Biochemical and Histopathological analysis of rats’ brain were estimated. Statistical analysis was done by one‑way analysis ofvariance, followed by post hoc Dunnett’s test. P less tha 0.05 was considered statistically significant. The results suggest that both the natural compounds α asarone and Glabridin has significantly improved cognitive functions in rats subjected to chronic restrain stress. The Corticosterone concentration was decreased in rats pre-treated with α asarone and Glabridin. The results of molecular docking and further animal study in pre treatment of rats with Glabridin and αasarone before exposure to chronic restrain stress showed observable neuroprotection and improved cognition that could be due to the antioxidant action of the compounds in the rat hippocampus. Hence, these two natural compounds could be an adjuvant therapy for treatment of neurodegenerative diseases. Hence we conclude that the two natural compounds play a role in neuronal stress adaptation mechanism and have potential to prevent progression of neurodegenerative diseases.