芍药甘草汤治疗多囊卵巢综合征高雄激素血症的网络药理学研究

Study on the Network Pharmacology of Shaoyao Gancao Decoction in the Treatment of Hyperandrogenism in Polycystic Ovary Syndrome

目的运用网络药理学探索芍药甘草汤对多囊卵巢综合征高雄激素血症的作用机理。方法通过TCMSP数据库结合口服生物利用度(OB)、类药性(DL)、半衰期(HL)筛选芍药甘草汤的有效活性成分及作用靶点,运用Genecards、Drugbank、OMIM数据库获取多囊卵巢综合征高雄激素血症的治疗靶点。借助Cytoscape3.7.2软件构建“中药-活性成分-靶点”可视化网络,利用VENNY图筛选出药物与疾病的共同靶点,运用STRING在线分析工具构建蛋白互作网络图(PPI),通过David数据库对关键靶点进行GO功能富集分析及KEGG通路富集分析。结果从芍药甘草汤中筛选出槲皮素、山奈酚、7-甲氧基-2-甲基异黄酮、刺芒柄花素等83个有效成分,作用于MAPK3、MMP-9、STAT3、TNF、IL-6、VEGFA等41个关键靶点。KEGG通路富集分析发现这些靶点参与了TNF、HIF-1、FoxO、Toll样受体等信号通路。结论芍药甘草汤中的槲皮素、山奈酚等可能通过TNF、IL-6、STAT3、VEGFA等靶点作用于TNF、HIF-1、FoxO、Toll样受体等信号通路来调节糖脂代谢、保护血管内皮、参与炎症反应,以减少雄激素的合成,发挥治疗多囊卵巢综合征高雄激素血症的作用。

Objective To explore the action pathway of Shaoyao Gancao Decoction on hyperandrogenism in polycystic ovary syndrome by network pharmacology.Methods The active ingredients and targets of Shaoyao Gancao Decoction were screened by TCMSP database combined with oral bioavail ability(OB),drug-like property(DL),and half-life period(HL).Genecards,Drugbank,and OMIM databases were used to obtain the targets of hyperandrogenism in polycystic ovary syndrome.Chinese medicine-active ingredient-target visualization network map was built by Cytoscape 3.7.2 software.VENNY diagram was used to screen out common targets of drugs and diseases.The protein interaction network(PPI)was constructed by STRING online analysis tool.The David database performed GO enrichment analysis and KEGG pathways analysis for key targets.Results 83 active components were screened and quercetin,kaempferol,7-methoxy-2-methyl isoflavone and formononetin were key compounds,41 key targets such as MAPK3,MMP-9,STAT3,TNF,IL-6,and VEGFA were founded.KEGG analysis indicated that these targets involved in TNF,HIF-1,FoxO,Toll-like receptors signaling pathways.Conclusion The main compounds such as quercetin,kaempferol could act on TNF,HIF-1,Toll-like receptors signaling pathways through TNF,IL-6,STAT3,VEGFA to regulate glycolipid metabolism,protect vascular endothelium and participate in inflammatory response thus reduce androgen synthesis and play a role in treating hyperandrogenism in polycystic ovary syndrome.