基于网络药理学和分子对接技术探讨四妙消痹汤治疗类风湿关节炎的作用机制

Mechanism of Simiao Xiaobi Decoction in Treatment of Rheumatoid Arthritis Based on Network Pharmacology and Molecular Docking Technology

目的:基于网络药理学和分子对接技术探讨四妙消痹汤治疗类风湿关节炎的作用机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)筛选四妙消痹汤组方中药活性成分及其相关靶点。通过GeneCards数据库、在线人类孟德尔遗传(online mendelian inheritance in man,OMIM)数据库、药物基因组学知识库(pharmacogenomics knowledgebase,PharmGKB)、药物靶标数据库(therapeutic target database,TTD)、DrugBank数据库搜索类风湿关节炎相关疾病靶点,与药物有效成分相关靶点进行映射,取交集即为四妙消痹汤治疗类风湿关节炎的潜在靶点,据此绘制Venn图。将潜在靶点导入STRING在线分析平台获得蛋白质相互作用(protein-protein interaction,PPI)网络,并利用Cytoscape软件中的CytoNCA插件对PPI网络进行拓扑分析,筛选得到核心靶点。利用R语言对潜在靶点进行基因本体(gene ontology,GO)功能富集分析和京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)信号通路富集分析。通过R语言对核心靶点和活性成分进行分子对接。结果:通过TCMSP检索获得四妙消痹汤有效活性成分190个及相关靶点215个。通过GeneCards、OMIM、PharmGKB、TTD及DrugBank数据库获得类风湿关节炎相关疾病靶点2971个,四妙消痹汤治疗类风湿关节炎的潜在靶点151个。PPI网络拓扑分析筛选得到核心基因JUN、MAPK1、FOS、TP53、ESR1等11种。GO富集分析得到2452条富集结果,其中生物过程2178条,分子功能62条,细胞组成212条,KEGG富集分析得到172条信号通路。分子对接结果表明,药物有效成分与核心靶点具有良好亲和力。结论:四妙消痹汤可通过多成分、多靶点、多途径对类风湿关节炎发挥作用。

Objective:To investigate the mechanism of Simiao Xiaobi Decoction in the treatment of rheumatoid arthritis based on network pharmacology and molecular docking technology.Methods:The traditional Chinese medicine active ingredients and related targets of Simiao Xiaobi Decoction were screened by traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP).Search rheumatoid arthritis through GeneCards database,online mendelian inheritance in man(OMIM)database,pharmacogenomics knowledgebase(PharmGKB),drug target database(TTD),DrugBank database The relevant disease targets are mapped with the targets related to the active ingredients of the drug,and the intersection is the potential target of Simiao Xiaobi Decoction in the treatment of rheumatoid arthritis,and the Venn diagram is drawn accordingly.The potential targets were imported into the STRING online analysis platform to obtain the protein-protein interaction(PPI)network,and the CytoNCA plug-in in Cytoscape software was used to perform topological analysis on the PPI network,and the core targets were obtained by screening.Gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis were performed on potential targets using R language.Molecular docking of core targets and active ingredients through R language.Results:190 active ingredients and 215 related targets of Simiao Xiaobi Decoction were retrieved by TCMSP.Through GeneCards,OMIM,PharmGKB,TTD and DrugBank databases,2971 rheumatoid arthritis-related disease targets were obtained,and 151 potential targets of Simiao Xiaobi Decoction in the treatment of rheumatoid arthritis.PPI network topology analysis screened 11 core genes including JUN,MAPK1,FOS,TP53 and ESR1.GO enrichment analysis obtained 2452 enrichment results,including 2178 biological processes,62 molecular functions,and 212 cellular components.KEGG enrichment analysis obtained 172 signaling pathways.Molecular docking results showed that the active ingredients of the drug had good affinity with the core target.Conclusion:Simiao Xiaobi Decoction can play a role in rheumatoid arthritis through multi-component,multi-target and multi-way.