基于网络药理学探讨振中汤治疗类风湿关节炎作用机制

Mechanism of Zhenzhong Decoction in treating rheumatoid arthritis based on network pharmacology

目的:采用网络药理学的方法,对振中汤治疗类风湿关节炎(rheumatic arthritis,RA)的作用机制进行探讨研究。方法:通过中药系统药理学数据库与分析平台(TCMSP)对振中汤活性成分进行筛选,运用Cytoscape3.8.2构建化合物-靶点网络;以“rheumatic arthritis”、“RA”为关键词,检索Drugbank和Genecard数据库获取疾病靶标;通过韦恩图,得到疾病与药物的共同靶点;基于String11.0和Analyze Network插件对振中汤治疗类风湿关节炎的关键靶点进行构建分析;采用WebGestalt富集分析工具对关键靶点进行基因本体(GO)功能注释和京都基因与基因组百科全书(KEGG)通路富集分析。结果:研究显示共挖掘到振中汤51种有效成分及234个潜在靶点,类风湿关节炎1223个相关靶点,得到振中汤-类风湿关节炎共同靶点120个,共同作用靶点主要富集于119个生物过程和104条信号通路上。结论:振中汤可能是通过原癌基因(JUN)、肿瘤坏死因子(TNF)、丝裂原活化蛋白激酶3(MAPK3)、白细胞介素-6(IL6)、蛋白激酶(ATK1)等靶点,调控TNF信号通路、AGE-RAGE信号通路、白介素-17信号通路、Toll样受体信号通路、HIF-1信号通路等,从而发挥抗炎、调节免疫、调节内分泌功能、抑制滑膜细胞增殖、减少破骨细胞生成、抗缺氧应激来治疗类风湿关节炎。

Objective:To study the mechanism of Zhenzhong Decoction in the treatment of rheumatic arthritis(RA)by means of network pharmacology.Methods:The active ingredients of Zhenzhong Decoction were screened on TCMSP platform,and the component target network was constructed by Cytoscape 3.8.2 software;the disease targets were retrieved in Drugbank and Genecard databases;the Wein map was constructed to intersect the disease and drug targets.Based on String11.0 and Analyze Network plug-in,the key targets of Zhenzhong Decoction in the treatment of rheumatic arthritis were constructed and analyzed;Webgestalt enrichment analysis tool was used to annotate the function of Gene Ontology(go)and analyze the enrichment of Kyoto Encyclopedia of genes and genomes(KEGG)pathway.Results:A total of 51 components and 234 potential targets of Zhenzhong Decoction,and 223 related targets of rheumatic arthritis were found.120 common targets of Zhenzhong Decoction and rheumatic arthritis were obtained.The targets of interaction were mainly concentrated in 119 biological processes and 104 signaling pathways.Conclusion:Zhenzhong Decoction may regulate TNF signaling pathway,AGE-RAGE signaling pathway,IL-17 signaling pathway,Toll-like receptor signaling pathway and HIF-1 signaling pathway through the targets of JUN,TNF,MAPK3,IL-6 and ATK1,so as to play the role of anti-inflammatory.It can regulate immunity,regulate endocrine function,reduce osteoclast production,and resist hypoxia stress in the treatment of rheumatoid arthritis.