Abstract

Acetylcholinesterase (AChE) inhibition and antioxidants are two common strategies for the treatment in the early stage of Alzheimer's Disease (AD). In this study, extracts from nine traditional Chinese medical (TCM) herbs were tested for anti-AChE activity by Ellman's microplate assay and cytotoxicity by CCK-8. Based on its excellent AChE inhibition effect and its lowest cytotoxicity, Schisandra chinensis (SC) extract was selected to do the mechanism research. SC extract protected pheochromocytoma (PC12) cells against H2O2-induced toxicity by improving the cell survival rate in a dose-dependent manner. And it also showed significant free radical (DPPH) scavenging activities, ferric reducing antioxidant power (FRAP), and 2,2′-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging. To confirm these results, the scopolamine-induced mice models were utilized in this study. Compared with the positive drug (piracetam), SC could also exhibit similar effects to alleviate the mice's cognitive deficits. Moreover, in the mice brain samples, the AChE activity and malondialdehyde (MDA) levels of SC-treatment group both showed a reverse as compared to model group. Taken together, these results all suggested that SC extract may be a potential therapeutic candidate for AD.

Highlights

  • With the rapid increase of population aging in recent years, senile dementia has become one of the most important public health problems in the world [1, 2]

  • Alzheimer’s disease (AD) has been verified to be a chronic neurodegenerative disease characterized by progressive memory loss and cognitive function impairment which is caused by the accumulation of senile plaques and neurofibrillary tangles in the brain [5, 6]

  • Acetylcholinesterase inhibitors such as galantamine and donepezil are employed to increase the concentration of acetylcholine in the brain and combat the loss of acetylcholine caused by the death of cholinergic neurons [9, 10]

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Summary

Introduction

With the rapid increase of population aging in recent years, senile dementia has become one of the most important public health problems in the world [1, 2]. Reductions in the activity of the cholinergic neuron were always been tested in AD patients, and one of the important strategies for the therapy is to reduce the degradation of acetylcholine in neuromuscular junctions Acetylcholinesterase inhibitors such as galantamine and donepezil are employed to increase the concentration of acetylcholine in the brain and combat the loss of acetylcholine caused by the death of cholinergic neurons [9, 10]. NMDA antagonist could reduce the glutamic acid-induced neurotoxicity by the inhibition of activity of NMDA to improve the cognitive function [11]. None of these therapies has significant effects on curing AD [12]. None of these therapies has significant effects on curing AD [12]. erefore, it is indispensable to develop more novel and effective drugs for AD

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