四妙丸对类风湿性关节炎和湿疹“异病同治”作用机制的网络药理学探讨

Exploration on Mechanisms of Simiao Wan in Treating Rheumatoid Arthritis and Eczema with Concept of “Treating Different Diseases with Same Method” Based on Network Pharmacology

目的运用网络药理学方法分析四妙丸治疗类风湿性关节炎和湿疹的活性成分、作用靶点及关键通路,探讨该方"异病同治"的作用机制。方法通过检索中药系统药理学分析平台(TCMSP)数据库并结合文献筛选四妙丸中的活性成分及其作用靶点;利用OMIM、GeneCards、Drugbank等数据库收集类风湿性关节炎和湿疹的疾病相关靶点;活性成分作用靶点与疾病靶点取交集得到四妙丸治疗类风湿性关节炎和湿疹的共同靶点。通过Cytoscape 3.7.1软件构建"中药-活性成分-疾病共同靶点"网络;运用STRING数据库构建共同靶点蛋白互作(PPI)网络。通过Metascape和DAVID数据库对共同靶点分别进行GO功能富集分析和KEEG通路富集分析。结果共筛选出四妙丸治疗类风湿关节炎和湿疹的共同靶点46个,对应四妙丸中的45种活性成分。四妙丸主要通过槲皮素、山柰酚、汉黄芩素、油酸、3β-乙酰氧基苍术酮等活性成分,对TNF、IL6、IL1B、CCL2、CXCL8等关键基因进行调控,实现对类风湿关节炎和湿疹的异病同治作用。其作用机制可能与细胞黏附、白细胞迁移、对脂多糖的反应等生物过程有关,并通过TNF信号通路、类风湿性关节炎、Toll样受体信号通路等相关通路实现。结论四妙丸是通过多成分、多靶点、多种信号通路来发挥治疗类风湿关节炎和湿疹的作用,与其抗炎及免疫调节作用密切相关。

Objective To analyze the active components,targets and key pathways of Simiao Wan(SMW)in the treatment of rheumatoid arthritis(RA)and eczema using the method of network pharmacology,so as to explore its mechanism of “treating different diseases with same method”.Methods The active compounds and targets of Simiao Wan were screened by retrieving the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database combined with literature screening.Targets related to RA and eczema can be obtained by OMIM,GeneCards and DrugBank database.The common targets of disease-drug were selected based on STRING database for protein-protein interaction(PPI)network construction.The Cytoscape software was used to map “herbscompounds-targets” network,while the targets were submitted to Metascape and DAVID database to analysis and annotate genes’ function and pathways.Results Finally,46 common targets of SMW treating RA and eczema and were screened out,and these targets were related to 45 candidate active compounds.Using “treating different diseases with same method” to treat RA and eczema by SMW is mainly achieved by regulating TNF,IL6,IL1 B,CCL2,CXCL8 and other hub genes by quercetin,kaempferol,wogonin and other active ingredients.The mechanism may be related to biological processes such as regulation of cell adhesion,leukocyte migration and response to lipopolysaccharide,and pathways including TNF signaling pathway,Rheumatoid arthritis,Toll-like receptor signaling pathway.Conclusion The result of the study preliminarily revealed characteristics of SMW in the treatment of RA and eczema with multi-component,multi-target and multi-pathway.It is closely related to antiinflammatory and immune regulation.