基于网络药理学研究麻杏苡甘汤治疗类风湿关节炎的作用机制

Action mechanism of Maxing Yigan Tang(麻杏苡甘汤) in the treatment of rheumatoid arthritis based on network pharmacology

目的运用网络药理学方法筛选麻杏苡甘汤治疗类风湿关节炎(RA)的作用机制。方法通过多个数据库筛选药物主要活性成分、靶点及与RA相关的疾病靶点,获取交集基因。采用Cytoscape 3.7.0软件构建麻杏苡甘汤治疗RA的成分-靶点-通路网络,采用STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,利用R语言对靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析。结果筛选出的药物核心成分为谷甾醇、槲皮素、木犀草素、查尔酮B、β-谷甾醇等,蛋白互作频次较高的靶点有丝氨酸/苏氨酸蛋白激酶(AKT1)、白细胞介素(IL)-6、血管内皮生长因子(VEGFA)、表皮生长因子(EGFR)、肿瘤坏死因子(TNF)等,与RA紧密联系的信号通路有磷脂酰肌醇3-激酶-蛋白激酶B(PI3K-Akt)、低氧诱导因子(HIF)-1、丝裂原活化蛋白激酶(MAPK)、Janus激酶-信号转导及转录活化因子通路(JAK-STAT)、RA、Wnt等。结论麻杏苡甘汤治疗RA具有多成分-多靶点-多途径的作用特点,为其进一步研究提供新的思路与线索。

Objective To screen out the action mechanism of Maxing Yigan Tang( 麻杏苡甘汤) in the treatment of rheumatoid arthritis( RA) based on network pharmacology. Methods The main active components,targets and RA-related disease targets of medicinal were screened out via multiple databases,whereby the intersection genes were obtained. The component-target-pathway network diagram of Maxing Yigan Tang in the treatment of RA was constructed by using Cytoscape 3.7.0 software,and the protein-protein interaction( PPI) network diagram was constructed by using Search Tool for the Retrieval of Interacting Proteins( STRING) database. Gene ontology( GO)function enrichment and and Kyoto encyclopedia of genes and genomes( KEGG) pathway enrichment analysis were performed by using R language. Results The core components of the medicinal screened out were sitosterol,quercetin,luteolin,chalcone B,β-sitosterol etc.,and the targets with higher frequency of PPI were serine/threonine protein kinase( AKT1),interleukin( IL)-6,vascular endothelial growth factor( VEGFA),epidermal growth factor receptor( EGFR),tumor necrosis factor( TNF) etc. Phosphatidyl inositol 3-kinase-protein kinase B( PI3 K-Akt),hypoxia inducible factor( HIF)-1,mitogen-activated protein kinase( MAPK),Janus-activated kinase/signal transducer and activator of transcription( JAK-STAT) signaling pathway,RA and Wnt were closely related to RA.Conclusion Maxing Yigan Tang in the treatment of RA has the action characteristics of multi-component,multi-target and multipathway,which provides new ideas and clues for its further research.