基于网络药理学探讨木防己汤治疗类风湿关节炎的作用机制

Study on Mechanism of Mufangji Decoction in the Treatment of Rheumatoid Arthritis Based on Network Pharmacology

目的采用网络药理学技术探讨木防己汤治疗类风湿关节炎(RA)的作用机制。方法通过在TCMSP平台对木防己汤进行活性成分筛选,在DrugBank、GeneCards、OMIM等数据库检索RA相关靶点。运用Venny2.1软件进行对比,筛选木防己汤与类风湿性关节炎的共同靶点,并绘制Venny图。利用Cytoscape3.7.2构建木防己汤单味药-有效成分-类风湿关节炎-交集靶点的生物网络。运用R语言软件(Rx644.0.4)对木防己汤与疾病共同靶基因中的蛋白进行GO功能富集分析和KEGG信号通路分析,获得显著富集的信号通路。结果共得到木防己汤中30个有效成分及56个潜在靶点,获取RA疾病相关靶点5046个,木防己汤-RA疾病共同靶点37个,GO功能分析共包含83条富集结果,KEGG分析共筛选出在治疗RA方面具有作用的90条通路。木防己汤主要成分β-谷甾醇、山柰酚,可能是调节PPARG、CASP3、RELA、ESR1、ICAM1等靶点,调控脂质和动脉粥样硬化、肿瘤坏死因子信号通路、弓形虫病、化学致癌-受体激活、流体剪切应力与动脉粥样硬化、前列腺癌、糖尿病并发症中的AGE-RAGE信号通路、乙型肝炎、甲型流感、细胞凋亡等信号通路。结论木防己汤对RA的治疗呈现多成分、多靶点、多通路的特点,研究结果初步推测木防己汤有效活性成分治疗类风湿关节炎的作用机制,为木防己汤治疗类风湿关节炎提供一定的理论依据。

Objective To explore the mechanism of Mufangji Decoction in treating rheumatoid arthritis(RA)by network pharmacology.Methods The disease-related targets were searched in DrugBank,GeneCards,OMIM and other databases by screening the active components of Mufangji Decoction on the TCMSP platform.Venny2.1 software was used for comparison to screen out the common targets of Mufangji Decoction and rheumatoid arthritis,and Venny diagram was drawn.Cytoscape 3.7.2 was used to construct a biological network of single herb-effective components-rheumatoid arthritis-intersecting targets of Mufangji Decoction.The R language software(Rx644.0.4)was used to perform GO functional enrichment analysis and KEGG signaling pathway analysis on the proteins in the common target genes of Mufangji Decoction and disease,and a significantly enriched signaling pathway was obtained.Results A total of 30 active ingredients and 56 potential targets in Mufangji Decoction were obtained,5046 RA disease-related targets were obtained,and 37 common targets of Mufangji Decoction-RA disease were obtained.GO functional analysis contained a total of 83 enrichment results.KEGG analysis screened 90 pathways that had a role in the treatment of RA.The main components of Mufangji Decoctionβ-sitosterol,kaempferol,may be the regulation of PPARG,CASP3,RELA,ESR1,ICAM1 and other targets,regulation of lipid and atherosclerosis,tumor necrosis factor signaling pathways,toxoplasmosis,chemical carcinogenesis-receptor activation,fluid shear stress and atherosclerosis,prostate cancer,diabetes complications in the AGE-RAGE signaling pathway,hepatitis B,influenza,apoptosis and other signaling pathways.Conclusion The treatment of RA by Mufangji Decoction presents the characteristics of multi-component,multi-target and multi-pathway.The results preliminarily speculate the mechanism of the effective active ingredients of Mufangji Decoction in the treatment of rheumatoid arthritis,and provide a theoretical basis for the treatment of rheumatoid arthritis by Mufangji Decoction.