基于网络药理学对黄连治疗多囊卵巢综合征高雄激素血症的分子机制研究
Network Pharmacology Research of Huanglian in Treatment of Polycystic Ovary Syndrome with Hyperandrogenism
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摘要: 目的 基于网络药理学阐述黄连治疗多囊卵巢综合征高雄激素血症(PCOS-HA)的可能分子机制。方法 借助TCMSP收集黄连的化合物及有效靶点,运用Cytoscape软件构建化合物-靶点网络;合并GeneCards、OMIM及CTD三库数据筛选的疾病靶点,与药物的有效靶点进行韦恩分析,确定交集靶点;用String数据库构建靶点蛋白互作网络;利用DAVID数据库进行基因功能GO分析和KEGG通路富集分析。结果 获得11个活性化合物,药物靶点111个,疾病靶点370个,交集靶点37个。蛋白互作网络(PPI)涉及30个蛋白节点,关键靶点包括FOS、JUN、IL-6、MAPK1、NCOA2、CCL2、ESR1、PPARA、CYP1A1、ESR2等。GO功能分析主要与转录调控、药物反应、RNA聚合酶Ⅱ启动子的调控、老化、类固醇激素介导的信号通路等相关。KEGG通路46条,主要涉及TNF信号通路、FoxO信号通路等。结论 通过网络药理学证实了单方中药黄连多成分、多靶点、多途径的作用特点,预测了黄连治疗PCOS-HA的可能作用机制,为进一步研究其活性成分和作用机制提供理论依据。Abstract: OBJECTIVE To explore the material basis and mechanism of Huanglian in the treatment of polycystic ovary syndrome with hyperandrogenism (PCOS-HA) based on network pharmacology. METHODS With the help of TCMSP to collect the compounds and effective targets of Huanglian, the compound-target network was constructed by Cytoscape software, the disease targets of the data screening of GeneCards, OMIM and CTD were collected, and the effective targets of the drug were analyzed by Venny to determine the intersection targets. The target protein interaction network was constructed with String database, and the gene function GO enrichment analysis and KEGG pathway enrichment analysis were carried out by DAVID database. RESULTS 11 active compounds, 111 drug targets, 370 disease targets and 37 intersecting targets were obtained. The PPI network involved 30 protein nodes, with key targets including FOS, JUN, IL-6, MAPK1, NCOA2, CCL2, ESR1. GO functional enrichment analysis was mainly related to positive regulation of transcription, response to drug, transcription initiation from RNA polymerase Ⅱ promoter, aging and so on. 46 KEGG Access were mainly involved TNF signaling pathway and FoxO signaling pathway. CONCLUSION The network pharmacology confirms the multi-component, multi-target and multi-pathway action characteristics of huanglian which predicts the possible mechanism of it in the treatment of PCOS-HA, and provides theoretical basis for further study of the active ingredients and mechanism.