金银花—大血藤治疗类风湿关节炎作用机制的网络药理学分析

Analysis on mechanism of action of Jinyinhua-Daxueteng in treatment of rheumatoid arthritis

目的分析金银花—大血藤药对治疗类风湿关节炎(RA)的机制。方法通过TCMSP、Genecards、OMIM、TTD等数据库获取金银花、大血藤药物作用及RA疾病靶点;基于Venny平台寻找药物靶点与疾病靶点交集;通过Cytoscape软件及VLOOKUP函数建立“药物—成分—关键靶点—疾病”网络;运用String数据库构建关键靶点的蛋白相互作用网络;对关键靶点进行GO分析和KEGG分析;将核心成分与核心靶点进行分子对接。结果金银花—大血藤药对靶点共323个,RA疾病靶点5093个,“药物—成分—关键靶点—疾病”网络中筛选出核心靶点PTGS1、PTGS2,核心成分包括丁香酚、大黄素、β-谷甾醇、熊果酸、山萘酚、木樨草素、三羟黄酮、槲皮素;金银花—大血藤药对主要通过AGE-RAGE信号通路、滑膜细胞凋亡信号通路、HIF-1信号通路、NF-κB信号通路、JAK-STAT信号通路及RAS信号通路等参与细胞对氮化合物的反应、淋巴细胞分化、生长因子调控、LPS诱导的炎症反应等过程的调控;分子对接结果显示,8个核心成分与2个核心靶点之间亲和作用较好。结论金银花—大血藤可能通过调节PTGS1、PTGS2表达从而减轻RA患者自身免疫紊乱导致的炎症反应。

Objective To analyze the mechanism of Jinyinhua-Daxueteng in the treatment of rheumatoid arthritis(RA).Methods The drug effects of Jinyinhua-Daxueteng and the disease targets of RA were obtained through databases such as TCMSP,Genecards,OMIM,TTD,etc.The intersection of drug targets and disease targets were searched based on the Venny platform.A"drug-component-key target-disease"network was established using Cytoscape software and VLOOKUP function.The protein-protein interaction network for key targets was constructed using String database.GO analysis and KEGG analysis were used on key targets.Core ingredients and core targets were used for molecular docking.Results A total of 323 targets were obtained from Jinyinhua-Daxueteng,and 5093 targets for RA disease were obtained.PTGS1 and PTGS2 core targets were screened from the"drug-component-key target-disease"network,including eugenol,emodin,β-Sitosterol,ursolic acid,kaempferol,luteolin,trihydroxyflavones and quercetin.Jinyinhua-Daxueteng mainly participated in the regulation of cellular response to nitrogen compounds,lymphocyte differentiation,growth factor regulation,LPS induced inflammatory response,through the AGE-RAGE signaling pathway,synovial cell apoptosis signaling pathway,HIF-1 signaling pathway,NF-κB signaling pathway,JAK-STAT signaling pathway,and RAS signaling pathway.The molecular docking results showed good affinity between the 8 core components and the 2 core targets.Conclusion Jinyinhua-Daxueteng may participate in alleviating the inflammatory response caused by autoimmune disorders in RA patients by regulating the expression of PTGS1 and PTGS2.