摘要
为了揭示远志治疗阿尔茨海默病的潜在活性成分群及其分子网络作用机制,本文收集了已报道的远志111个化学成分,经过口服吸收利用度、类药性和血脑屏障通透性筛选,得到远志中10个活性分子,其中口山酮类化合物3个、皂苷类化合物1个、寡糖酯类化合物3个和其他类3个。继而运用反向药效团匹配的方法进行靶点预测,经验证得到与阿尔茨海默病相关靶点13个,其中核心靶点2个,即beta-secretase 1和glycogen synthase kinase-3 beta;利用KEGG数据库与GO富集分析进一步挖掘远志防治阿尔茨海默病的分子网络机制,得到映射代谢调控通路3条,主要通路为细胞凋亡通路。本文应用系统药理学的方法发现远志中的多种活性成分通过与多个靶点的相互作用,多通路调控Aβ的生成与细胞的凋亡,进而起到治疗阿尔茨海默病的作用,为远志治疗阿尔茨海默病的临床使用提供一定的科学依据。
This study was designed to investigate the molecular mechanism and potential active constituents of Polygala Radix in the treatment of Alzheimer＇s disease with multiple data bases combined with literature mining to build Polygala Radix chemical composition database. A novel analysis tool Pharmmapper was used to obtain the main active ingredient and potential target of Polygala Radix. By extensive data profiling, the Polygala Radix was found to contain 111 chemical constituents. Among them, a total of 10 active molecules included 3 xanthone, 1 saponins, 3 oligosaccharide esters, and 3 other classes were related to 13 Alzheimer＇s disease-related targets. Two of the core targets were beta-secretase 1 and glycogen synthase kinase-3 beta. Use the GO analysis and KEGG to explore the molecular mechanism of Polygala Radix in treatment of Alzheimer＇s disease, which has 3 signaling pathways, and the most important signaling pathway is the cell death signaling pathway. The active constituents of Polygala Radix could control the formation of Aβ and the apoptosis of cells through the interaction with multiple targets, and control the treatment of Alzheimer＇s disease.
作者
王昊
赵振宇
沈霞
胡本祥
陈莹
WANG Hao ZHAO Zhen-yu SHEN Xia HU Ben-xiang CHEN Ying(School of Pharmaceutical Science, Shaanxi University of Traditional Chinese Medicine, Xianyang 712046, China)
出处
《药学学报》
CAS
CSCD
北大核心
2017年第10期1554-1560,共7页
Acta Pharmaceutica Sinica
基金
国家中医药管理局资助项目(2015468002-1)
2015陕西省教育厅重点科研计划(15JS023)
关键词
远志
系统药理学
阿尔茨海默病
分子机制
虚拟筛选
Polygala Radix
system pharmacology
Alzheimer＇s disease
mechanism
virtual screening
