独活寄生汤治疗膝骨性关节炎分子机制的网络药理学探讨

Molecular mechanism of Duhuojisheng Decoction in the treatment of knee osteoarthritis based on the network pharmacology

目的:运用网络药理学的方法探讨独活寄生汤治疗膝骨性关节炎(knee osteoarthritis,KOA)的分子机制。方法:通过TCMSP数据库、Batman-TCM数据库检索独活寄生汤中独活、桑寄生、杜仲、牛膝、细辛、秦艽、茯苓、肉桂、防风、川芎、人参、甘草、当归、白芍、生地黄中含有的化合物,筛选其活性成分及其作用靶点;通过GeneCards和CTD数据库获取KOA的相关靶标;采用Cytoscape 3.7.2软件构建“药物-化合物-靶点”网路,STRING数据库进行PPI网络的构建与分析;利用DAVID数据库进行GO分析和KEGG富集分析(P<0.05)。结果:筛选后共获得独活寄生汤治疗KOA的217个成分和155个靶点;KOA相关靶点5653个;PPI核心网络共79个蛋白,关键蛋白涉及INS、IL6、TNF、VEGFA等;获得301条GO生物过程和114条相关信号通路,涉及类风湿关节炎、破骨细胞分化、MAPK信号通路、HIF-1信号通路、PI3K-Akt信号通路、TNF信号通路等。结论:独活寄生汤可能通过调控细胞增殖与凋亡、炎症反应等治疗KOA,是多成分、多靶点、多通路相互作用的结果,为独活寄生汤治疗KOA提供了理论支持。

Objective:To explore the molecular mechanism of Duhuojisheng Decoction in the treatment of knee osteoarthritis(KOA).Methods:Through tcmsp database and Batman TCM database,the compounds in Duhuo Jisheng decoction,such as Duhuo,sangparasitic,eucommia,Achyranthes bidentata,asarum,Gentiana macrophylla,Poria cocos,cinnamon,Fangfeng,chuanxiong,ginseng,liquorice,angelica,white peony and raw rehmannia,were searched,and their active components and targets were screened.The target of KOA was acquired by database,and the drug compound target network was constructed by using the software of cycloscape 3.7.2.PPI network was constructed and analyzed by using string database.While go analysis and KEGG enrichment analysis were conducted by using David database(P<0.05).Results:After screening,217 components and 155 targets were obtained for the treatment of KOA;5653 targets were related to KOA;79 proteins were related to PPI core network,including INS,IL6,TNF and VEGFA;301 go biological processes and 114 related signal pathways were obtained,including rheumatoid arthritis,osteoclast differentiation,MAPK signal pathway,HIF-1 signal pathway and PI3K Akt signal pathway,TNF signal pathway,etc.Conclusions:Duhuo parasitic decoction may regulate cell proliferation,apoptosis and inflammatory response to treat KOA,which is the result of multi-component,multi-target and multi-channel interaction,providing theoretical support for Duhuo parasitic Decoction to treat KOA.