基于网络药理学和分子对接法探索如意金黄膏治疗炎性外痔的潜在有效成分及作用机制

Exploration of potential effective components and mechanism of Ruyi Jinhuang ointment in the treatment of inflammatory external hemorrhoids based on network pharmacology and molecular docking

目的探讨如意金黄膏治疗炎性外痔(IEH)的潜在有效成分及作用机制。方法运用中药系统药理学分析平台数据库(TCMSP)与文献挖掘获取如意金黄膏的有效成分和对应的作用靶点,在GeneCards、OMIM数据库获得IEH的靶点。采用Cytoscape 3.7.2软件构建药物活性成分-预测靶点网络并进行分析,运用Cytoscape 3.7.2软件中BisoGenet插件构建蛋白质相互作用(PPI)网络,并采用AutoDock Vina软件进行分子对接验证;采用Bioconductor生物信息资源数据库对关键靶点进行GO和KEGG富集分析。结果通过筛选得到179个活性成分、2576个成分作用靶点、307个IEH相关靶点和40个如意金黄膏-IEH共同靶点。PPI网络分析结果表明,如意金黄膏治疗IEH关键靶点包括PTGS2、ESR1和AR等,富集分析共获得1203个GO条目和98条IEH相关通路,主要涉及肿瘤坏死因子(TNF)、前列腺癌和内分泌抵抗等信号通路。分子对接结果显示,如意金黄膏中槲皮素、汉黄芩素、山柰酚等关键化合物与PTGS2、ESR1、AR等核心靶点有较好的亲和力。结论本研究从网络药理学角度初步预测如意金黄膏治疗IEH的物质基础和作用机制,为其临床应用提供理论基础。

Objective To investigate the potential effective components and mechanism of Ruyi Jinhuang ointment in the treatment of inflammatory external hemorrhoids(IEH). Methods The effective components and corresponding targets of Ruyi Jinhuang ointment were retrieved from the traditional Chinese medicines systems pharmacology platform(TCMSP)and literatures. The targets of IEH were obtained from GeneCards and OMIM database. The ative components of drugs-predictive targets network was constructed and analyzed by Cytoscape 3.7.2 software. The protein-protein interaction(PPI) network was constructed by BisoGenet plug-in in Cytoscape 3.7.2 software, and the molecular docking was verified by AutoDock Vina software. GO and KEGG enrichment analysis were conducted by Bioconductor bioinformatics resource database. Results A total of 179 active components, 2 576 target points, 307 IEH related targets and 40 Ruyi Jinhuang ointment-IEH common targets were obtained by screening. PPI network analysis result showed that the key targets of Ruyi Jinhuang ointment in the treatment of IEH included PTGS2, ESR1, AR and so on. A total of 1 203 GO entries and98 IEH related pathways were obtained by enrichment analysis, mainly involving tumor necrosis factor(TNF) signaling pathway, prostate cancer, endocrine resistance and so on. Molecular docking results showed that key compounds such as quercetin, wogonin and kaempferol in Ruyi Jinhuang ointment had good affinity with PTGS2, ESR1, AR and other core targets. Conclusion This study preliminarily predicted the material basis and mechanism of Ruyi Jinhuang ointment in the treatment of IEH from the perspective of network pharmacology, to provide a theoretical basis for its clinical application.