昆明山海棠-鸡血藤药对治疗类风湿关节炎作用机制的网络药理学研究
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篇名: 昆明山海棠-鸡血藤药对治疗类风湿关节炎作用机制的网络药理学研究
TITLE:
摘要: 目的:研究昆明山海棠-鸡血藤药对治疗类风湿关节炎的作用机制。方法:通过检索治疗靶点数据库(TTD)、药物银行(DrugBank)和DisGeNET数据库获取类风湿关节炎靶点,并构建靶点互作(PPI)网络筛选关键靶点。以口服生物利用度(OB)≥30%、类药性(DL)≥0.18、半衰期(HL)≥4 h为指标,借助中药系统药理学数据库及分析平台(TCMSP)和中药综合数据库(TCMID)获取昆明山海棠-鸡血藤药对的活性成分,并预测其靶点,构建昆明山海棠-鸡血藤药对活性成分-靶点网络;借助Systems Dock Web Site在线平台、Genomics平台筛选昆明山海棠-鸡血藤药对的活性成分和类风湿关节炎的共有靶点,然后利用Cytoscape 3.2.1软件中Cluego插件分析共有靶点的京都基因与基因组百科全书(KEGG)信号通路。结果:共检索到类风湿关节炎靶点1 956个,其中关键靶点11个[包括白细胞介素6(IL-6)、肿瘤坏死因子(TNF)、血管内皮生长因子A(VEGFA)等];昆明山海棠-鸡血藤药对共筛选出30种活性成分(包括木犀草素、芒柄花黄素、β-谷甾醇、雷公藤甲素等)和229个靶点。昆明山海棠-鸡血藤药对和类风湿关节炎的共有靶点有37个[包括基质金属蛋白2(MMP2)、 TNF、VEGFA等];参与的KEGG信号通路有细胞凋亡、IL-17信号通路、Th17细胞分化信号通路、TNF信号通路等。结论:昆明山海棠-鸡血藤药对可能通过MMP2、TNF、VEGFA等靶点作用于细胞凋亡、IL-17信号通路等多条信号通路发挥治疗类风湿关节炎的作用,本研究结果可为进一步研究昆明山海棠-鸡血藤药对治疗类风湿关节炎的作用机制提供参考。
ABSTRACT: OBJECTIVE: To study the mechanism of couplet medicine of Tripterygium hypoglaucum-Spatholobus suberectus in the treatment of rheumatoid arthritis (RA). METHODS: The RA targets were retrieved and obtained by therapeutic target database (TTD), DrugBank and DisGeNET databases, and the protein protein interaction (PPI) network was constructed to screen its key targets. Using oral bioavailability(OB)≥30%, drug like(DL)≥0.18 and drug half-life (HL) ≥4 h as index, active components were obtained from couplet medicine of T. hypoglaucum-S. suberectus by using TCM systematic pharmacological analysis platform (TCMSP) and TCM integrated database (TCMID), and the targets were predicted. The active component-target network of couplet medicine of T. hypoglaucum-S. suberectus was constructed. Systems Dock Web Site online platform and Genomics platform were used to screen the active component and common targets of RA of couplet medicine of T. hypoglaucum-S. suberectus; KEGG signaling pathways of common targets were analyzed by using Cluego plug-in unit of Cytoscape 3.2.1 software. RESULTS: Totally 1 956 RA targets were retrieved, involving 11 key targets [such as IL-6, TNF, VEGFA]. The couplet medicine contained 30 active components (including luteolin, erythroxanthin, β-sitosterol and triptolide) and 229 targets. There were 37 common targets for couplet medicine of T. hypoglaucum-S. suberectus and RA (including MMP2, TNF, VEGFA). KEGG signaling way involved cell apoptosis, IL-17 signaling pathway, Th17 cell differentiation pathway and TNF signaling pathway. CONCLUSIONS: The couplet medicine of T. hypoglaucum-S. suberectus may play a role in the treatment of RA by acting on cell apoptosis, IL-17 signaling pathway and other signaling pathways through MMP2, TNF, and VEGFA target. The results of this study can provide a reference for further study on the mechanism of the effects of couplet medicine of T. hypoglaucum-S. suberectus on RA.
期刊: 2019年第30卷第19期
作者: 刘丹凯,王强,魏赈权,刘小宝,郑雪霞,钱凯,曾丽盈,许舒迪,林昌松
AUTHORS: LIU Dankai,WANG Qiang,WEI Zhenquan,LIU Xiaobao,ZHENG Xuexia,QIAN Kai,ZENG Liying,XU Shudi,LIN Changsong
关键字: 类风湿关节炎;昆明山海棠-鸡血藤药对;网络药理学;作用机制;信号通路
KEYWORDS: Rheumatoid arthritis; Couplet medicine of Tripterygium hypoglaucum-Spatholobus suberectus; Network pharmacology; Mechanism; Signaling pathways
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