基于网络药理学的固本健脑液防治阿尔兹海默病的活性成分与作用机制研究  

Network Pharmacology-based Study on Mechanism of Guben-Jiannao Liquid in Treatment of Alzheimer’s Disease

作　　者：毛剑琴 袁德培 张誉丹 覃亚 Mao Jianqin;Yuan Depei;Zhang Yudan;Qin Ya(Hubei Minzu University,Enshi 445000,China;Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic Diseases,Enshi 445000,China)

机构地区：[1]湖北民族大学,湖北恩施445000 [2]湖北民族大学风湿病发生与干预湖北省重点实验室,湖北恩施445000

出　　处：《湖北民族大学学报（医学版）》2020年第2期4-9,共6页Journal of Hubei Minzu University(Medical Edition)

基　　金：国家自然科学基金(81860811)。

摘　　要：目的基于中药网络药理学预测固本健脑液防治阿尔兹海默病(AD)的主要活性成分与作用靶点,探讨其"多成分-多靶点-多通路"的作用机制。方法通过GeneCards数据库、OMIM数据库收集AD治疗靶点;根据中药系统药理学技术平台(TCMSP)构建固本健脑液中药的化学成分及靶蛋白;找到固本健脑液与AD的靶蛋白交集,构成Venn图;采用Cytoscape 3.7.1软件构建固本健脑液的"成分-靶点-通路"网络;运用string数据库绘制PPI网络;通过R和Bioconductor软件对虚拟筛选到的关键靶蛋白进行GO和KEGG富集分析。结果从固本健脑液中筛选出了76个化合物,这些有效成分可能通过调节PGR、NR3C2、PTGS2、RXRA、ADRB2、CHRM3等459个潜在靶蛋白而发挥作用,涉及P53信号通路、EGFR信号通路、TNF信号通路、PI3K-AKT信号通路、人巨细胞病毒感染信号通路、卡波西肉瘤相关疱疹病毒感染信号通路等187条通路。结论固本健脑液中的灌木远志酮A、川芎哚、7,9(11)-去氢茯苓酸甲酯等活性成分,可能是防治AD的物质基础,其作用机制涉及感染及凋亡途径的阻断等。Objective This study was designed to predict the main targets of Guben-Jinnao Liquid in Alzheimer’s disease based on network pharmacology methods,and to explore its“multi-component,multi-target,and multi-pathway”mechanism.Methods According to the GeneCards Database、Online Mendelian Inheritance in Man(OMIM)Database,targets for treating Alzheimer’s disease were collected.According to the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),the library of chemical constituents and target protein of Indigo Naturalis was established,target protein intersection of Guben-Jiannao Liquid and Alzheimer’s disease was figured out and a Venn diagram was got.The network of“compound-target proteins-pathway”was built by using the Cytoscape 3.7.1 software,protein interaction network(PPI network)was built by using string Database,enrichment of functions and signaling pathways of the Virtual screening key target proteins was conducted by R and Bioconductor software.Results The 76 active compounds were selected from Guben-Jiannao Liquid.These active ingredients may regulate 459 potential target proteins such as PGR、NR3C2、PTGS2、RXRA、ADRB2、CHRM3 to play a role in the pathogenesis of Alzheimer’s disease.The results also suggested that 187 signaling pathways were involved in the pathogenesis of Alzheimer’s disease,such as P53 signaling pathway,EGFR signaling pathway,TNF signaling pathway,PI3K-AKT signaling pathway,Human cytomegalovirus infection,Kaposi sarcoma-associated herpes virus infection signaling pathway and so on.Conclusion This research method initially revealed that the active ingredients of Shrub hygenone A,ligustrondoles,7,9(11)-methyl dehydroporia acid in Guben-Jiannao Liquid are the material basis for the treatment of Alzheimer’s disease.Its mechanism of action involved inflammatory,blocking of apoptotic pathway and so on.

关 键 词：网络药理学 固本健脑液 阿尔兹海默病 

分 类 号：R285.5[医药卫生—中药学]