文章基本信息

标题：Discovery of Natural Inhibitors of Cholinesterases from Hydrangea: In Vitro and In Silico Approaches
本地全文：下载
作者：Jayeong Hwang ; Kumju Youn ; Gyutae Lim 等
期刊名称：Nutrients
电子版ISSN：2072-6643
出版年度：2021
卷号：13
期号：1
页码：254
DOI：10.3390/nu13010254
出版社：MDPI Publishing
摘要：Alzheimer’s disease (AD) is a neurodegenerative disease conceptualized as a clinical-biological neurodegenerative construct where amyloid-beta pathophysiology is supposed to play a role. The loss of cognitive functions is mostly characterized by the rapid hydrolysis of acetylcholine by cholinesterases including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Moreover, both enzymes are responsible for non-catalytic actions such as interacting with amyloid β peptide (Aβ) which further leads to promote senile plaque formation. In searching for a natural cholinesterase inhibitor, the present study focused on two isocoumarines from hydrangea, thunberginol C (TC) and hydrangenol 8-O-glucoside pentaacetate (HGP). Hydrangea-derived compounds were demonstrated to act as dual inhibitors of both AChE and BChE. Furthermore, the compounds exerted selective and non-competitive mode of inhibition via hydrophobic interaction with peripheral anionic site (PAS) of the enzymes. Overall results demonstrated that these natural hydrangea-derived compounds acted as selective dual inhibitors of AChE and BChE, which provides the possibility of potential source of new type of anti-cholinesterases with non-competitive binding property with PAS.
关键词：Alzheimer’s disease (AD); cholinesterase; molecular docking; thunberginol C; hydrangenol 8- O -glucoside pentaacetate Alzheimer’s disease (AD) ; cholinesterase ; molecular docking ; thunberginol C ; hydrangenol 8- O -glucoside pentaacetate