钩藤散活性成分治疗阿尔茨海默病作用机制的网络药理学分析  

Network pharmacological approach to investigate mechanism of active ingredients in Gouteng Powder for Alzheimer's disease

作　　者：宋祯彦[1] 陈易璇 余婧萍 贺旭[1] 成绍武[1] SONG Zhen-yan;CHEN Yi-xuan;YU Jing-ping;HE Xu;CHENG Shao-wu(Key Laboratory of Integrated Traditional Chinese and Westem Medicine on Prevention and Treatment of Cardio-Cerebral Diseases of Hunarl Province,Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学中西医结合心脑疾病防治湖南省重点实验室,湖南长沙410208

出　　处：《中草药》2018年第24期5854-5864,共11页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金面上项目(81774129);湖南省中医药管理局科研项目(2018025);湖南省中医药管理局重点项目(201609);湖南省教育厅开放基金重点项目(15K088);湖南省自然科学基金面上项目(2018JJ2296);湖南省科技厅重点专项(2017SK2111);2018年湖南中医药大学大学生研究性学习和创新性实验计划课题(2018017)

摘　　要：目的利用网络药理学方法研究钩藤散治疗阿尔茨海默病(AD)的作用机制。方法从中药系统药理学数据库(TCSMP)、中药信息数据库(TCMID)中筛选钩藤散治疗AD的活性成分,并构建药物-靶标-疾病网络、蛋白与蛋白相互作用(PPI)网络,运用生物信息学分析方法进行GO分析、通路富集分析和PPI网络分析。结果通过网络药理学方法筛选出钩藤散活性成分65种,显示其活性化合物的预测靶点473个,215个靶点与AD相关,钩藤散活性化合物的药效作用靶点高度富集到与AD相关的信号通路和生物学过程,PPI网络结果显示JUN、TNF、VEGFA、ESR1、APP可能是钩藤散治疗AD的重要作用靶点。结论钩藤散活性化合物以协同的方式与多个靶点、多种途径相互作用,主要通过抗炎、抗凋亡、增强代谢和增强免疫系统等途径对AD产生重要的治疗作用。Objective To confirm evidence regarding the potential therapeutic effect of Gouteng Powder(GTP) on Alzheimer's disease(AD) using a network pharmacological approach. Methods The active ingredients of GTP on AD were screened from Traditional Chinese Medicine Systems Pharmacology database and analysis platform(TCMSP) and Traditional Chinese Medicine Integrative Database(TCMID) by network pharmacology method, and the drugs-targets-diseases network and PPI network were built. These findings were confirmed by compound-target network, PPI network, gene ontology(GO) analysis, and KEGG pathway enrichment analysis. Results A total of 65 active ingredients from GTP were selected from TCMSP, which were interacted with 473 target proteins, and 215 potential targets related to AD were selected. Results showed that the compounds in GTP were highly connected to AD related signaling pathways and biological processes. PPI network results showed that JUN, TNF, VEGFA, ESR1, and APP might be important therapeutic targets of GTP in the treatment of AD. Conclusion Our results indicated that active compounds in GTP interacted with multiple targets in a synergetic way. The anti-inflammatory, anti-apoptosis, metabolic enhancement, and immune system enhancing effects of active ingredients in GTP might contribute its major therapeutic effects on AD.

关 键 词：网络药理学 钩藤散 阿尔茨海默病 作用机制 靶点 

分 类 号：R285.5[医药卫生—中药学]