中草药2026，Vol.57Issue(19)：7532-7540,9.DOI:10.7501/j.issn.0253-2670.2026.19.004
多裂骆驼蓬中乙酰胆碱酯酶抑制剂的靶向筛选及其抑制作用机制
Targeted screening of acetylcholinesterase inhibitors from Peganum multisectum and their mechanisms of inhibition
摘要
Abstract
Objective To screen acetylcholinesterase(AChE)inhibitors from the specific medicinal herbs Peganum multisectum by affinity ultra-filtration-liquid chromatography-mass spectrometry(AUF-LC-MS),and to explore their inhibition mechanisms.Methods The AChE inhibitory activities of various polar fractions of P multisectum were evaluated by Ellman's test,and the active components were precisely screened by AUF-LC-MS.The action mechanisms of the active components on AChE were investigated by enzyme inhibition kinetics,molecular docking and molecular dynamics simulations.Results A total of seven active components,including one flavonoid and six alkaloids,were identified from the dichloromethane and n-butanol fractions.Enzyme inhibition kinetics suggested that these components belonged to three inhibition types:reversible competitive inhibition(linarin),non-competitive(vasicine,vasicinone and harmol),and reversible mixed inhibition(deoxyvasicine,deoxyvasicinone and harmaline).Molecular docking results revealed that all compounds exhibited good affinities to AChE.And the binding sites and interaction forces of these inhibitors with AChE differed.Molecular dynamics simulation indicated that the system had reached a stable state,and the inhibitors had strong and stable interactions with AChE.Conclusions This study provided a scientific basis for elucidating the potential of P.multisectum in the prevention and treatment of Alzheimer's disease and offered a new reference for the discovery of high-efficiency AChE inhibitors.关键词
阿尔茨海默病/乙酰胆碱酯酶抑制剂/多裂骆驼蓬/亲和超滤-液质联用/抑制机制/蒙花苷/鸭嘴花碱Key words
Alzheimer's disease/acetylcholinesterase inhibitors/Peganum multisectum(Maxim.)Bobr./affinity ultra-filtration-liquid chromatography-mass spectrometry/inhibition mechanism/linarin/vasicine分类
医药卫生引用本文复制引用
郭炎峰,付小珊,李霄,黄丹蓉,赵思同,张爱芹,申刚义..多裂骆驼蓬中乙酰胆碱酯酶抑制剂的靶向筛选及其抑制作用机制[J].中草药,2026,57(19):7532-7540,9.基金项目
国家自然科学基金项目(82374161) （82374161）
中央高校基本科研业务费-中央民族大学交叉学科研究专项(2024JCYJ09) （2024JCYJ09）
北京市级大学生科学研究与创业行动计划项目(BEIJ2024110151) （BEIJ2024110151）
