淫羊藿治疗类风湿关节炎作用机制的网络药理学分析

目的运用网络药理学方法探讨淫羊藿治疗类风湿关节炎(RA)的作用机制。方法利用中药系统药理学技术平台(TCMSP)数据库收集淫羊藿的主要活性成分及其作用靶点;通过GeneCards、OMIM等数据库获取RA相关疾病靶点。取淫羊藿活性成分靶点与RA疾病靶点的交集基因(共同靶点),作为淫羊藿对RA作用的潜在关键靶点基因。将交集基因上传至String数据库,构建淫羊藿活性成分与RA疾病的共同靶点蛋白互作(PPI)网络,并根据其度值筛选出核心靶点。借助DAVID分析平台对共同靶点进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果共获得淫羊藿活性成分23个,共同靶蛋白即关键靶标72个。重要活性成分包括槲皮素(Quercetin)、木犀草素(Luteolin)、山萘酚(Kaempferol)等;核心靶点包括白细胞介素6(IL-6)、血管内皮生长因子A(VEGFA)、半胱氨酸蛋白酶3(CASP3)、表皮生长因子受体(EGFR)、丝裂原活化蛋白激酶8(MAPK8)等;KEGG主要通路富集在肿瘤坏死因子(TNF)信号通路、磷脂酰肌醇3激酶/蛋白激酶B(PI3K-Akt)信号通路、促乳素(Prolactin)信号通路、甲状腺激素(Thyroid hormone)信号通路、缺氧诱导因子1(HIF-1)信号通路等。结论淫羊藿可能主要通过多成分、多靶点、多通路,从调节炎症、免疫等多方面发挥对类风湿关节炎的治疗作用。

Study on the Mechanism of Epimedii Folium in the Treatment of Rheumatoid Arthritis Based on Network Pharmacology

Objective To explore the mechanism of Epimedii folium in the treatment of rheumatoid arthritis(RA)using the method of network pharmacology.MethodsCollection of main active components and target genes of Epimedii folium was achieved by using TCMSP database of traditional Chinese medicine system pharmacology technology platform. The disease target genes of RA were obtained through GeneCards and OMIM databases. The component targets and disease targets were uploaded to String database to construct the interaction network of traditional Chinese medicine component target and disease target proteins, and the key targets were selected according to their Degrees. With the help of DAVID analysis platform, the key targets were analyzed by gene ontology(GO)analysis and genome encyclopedia(KEGG)pathway enrichment analysis.ResultsA total of 23 active components of Epimedii folium were obtained,and 72 key targets of intersection with RA were obtained. Quercetin,luteolin, kaempferol, and other important active ingredients were analyzed. Core targets include IL-6, VEGFA,CASP3,EGFR,MAPK8 and other corresponding genes,which were mainly enriched in TNF signaling pathway,PI3 K-Akt signaling pathway, Prolactin signaling pathway, Thyroid hormone signaling pathway, HIF-1 signaling pathway and other signal pathways.ConclusionEpimedii folium may play a therapeutic role for rheumatoid arthritis mainly through regulating multiple components,multiple targets and multiple pathways from the aspects of regulating inflammation,immunity,etc.