基于网络药理学和生物信息学探讨满药复方木鸡颗粒治疗肝癌的分子机制

Study on Mechanism of Compound Muji Granule of Manchu Medicine in the Treatment of Liver Cancer Based on Network Pharmacology and Bioinformatics

利用网络药理学和生物信息学方法揭示复方木鸡颗粒治疗肝癌的作用机制。通过TCMSP、Swiss Target Prediction数据库分别获取复方木鸡颗粒的活性成分以及相关靶点;在GEO数据库筛选肝癌的相关靶点;利用Venny 2.1在线平台获取药物与疾病的共同靶点;由Cytoscape 3.8.2绘制药物–成分–靶点–疾病网络;用STRING数据库构建PPI网络;通过DAVID数据库进行GO功能富集和KEGG通路富集分析;利用Kaplan Meier-Plotter数据库对关键基因的表达量及预后关联性进行分析;运用AutoDock软件对关键成分和靶点进行分子对接验证。复方木鸡颗粒中共获得37个活性成分,筛选出57个共有靶点,涉及生物过程98条、细胞成分17条、分子功能37条,介导15条信号通路。生存期分析结果显示,ESR1、CYP3A4、G6PD基因的表达量与肝癌患者的生存期具有相关性。分子对接表明筛选的6个活性成分与6个关键靶点蛋白之间具有较好的结合能力。复方木鸡颗粒中的大豆皂苷C、柚皮素、β-谷固醇、汉黄芩素等活性成分可以作用于ESR1、CYP3A4、G6PD等靶点,可能通过P53、戊糖磷酸途径、MAPK等信号通路发挥治疗肝癌的作用。

Methods of network pharmacology and bioinformatics were utilized to predict the mechanism of compound Muji granule of Manchu medicine in the treatment of liver cancer.The active ingredients and corresponding targets of compound Muji granule were collected by TCMSP and Swiss Target Prediction database.The related targets of liver cancer were screened through the GEO database.Venny 2.1 online software was used to obtain the common targets of drugs-disease,and then the“drug-compound-targetdisease”network diagram was constructed by using the software Cytoscape 3.8.2.The STRING database was used to draw the protein-protein interaction network,and the perform GO function and KEGG pathway enrichment analysis were carried out through DAVID database.The relationship between the expression of key target genes and the survival curve was analyzed by using the Kaplan Meier-Plotter database,and the AutoDock platform was applied in verifying the molecular docking of active components and core protein targets.A total of 37 active components were obtained from compound Muji granule,and 57 common targets were screened,involving 98 biological processes,17 cellular components,37 molecular functions,and 15 signal pathways.The results of survival curve analysis show that the expression levels of ESR1,CYP3A4,and G6PD were related to the survival time of liver cancer patients.It was indicated that 6 active components and 6 key targets had a certain degree of binding through molecular docking.The active compounds in compound Muji granule,subprogenin C,naringenin,beta-sitosterol and wogonin,can act on targets such as ESR1,CYP3A4 and G6PD,which may play a therapeutic role in liver cancer by regulating p53,pentose phosphate,MAPK and other signaling pathways.