寿胎丸治疗早发性卵巢功能不全的网络药理学研究

目的:探讨寿胎丸治疗早发性卵巢功能不全的网络药理学特征。方法:利用中药系统药理学数据库与分析平台(TCMSP)、中医分子机制生物信息学分析工具(BATMAN-TCM)、GeneCards数据库获得寿胎丸活性成分及疾病靶点,利用Venn在线工具筛选二者交集基因,依托STRING数据库,采用Cytoscape 3.7.0软件构建活性成分-靶点网络图和靶点间蛋白质-蛋白质相互作用(PPI)网络图;通过DAVID数据库对交集基因进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,构建活性成分-靶点-关键通路网络图来展示寿胎丸治疗早发性卵巢功能不全的相关作用机制。结果:筛选出寿胎丸活性成分21个,成分靶点591个及疾病靶点2 438个,主要化合物有槲皮素、赖氨酸等。获得交集基因共67个,寿胎丸可能通过过氧化氢酶(CAT)、表皮生长因子(EGF)等靶点发挥作用,GO分析结果显示,其生物过程主要是药物反应,细胞组分主要是血红素结合反应,分子功能主要集中在线粒体基质。主要涉及的相关信号通路有缺氧诱导因子1(HIF-1)信号通路,磷脂酰肌醇3激酶/蛋白激酶B(PI3K-AKT)信号通路。结论:寿胎丸的多种活性成分可能作用于CAT、EGF等相关靶点,通过HIF-1、PI3K/AKT等主要信号通路,多靶点、多通路的发挥治疗早发性卵巢功能不全的作用。

A Network Pharmacological Study of Shou Tai Pills in the Treatment of Premature Ovarian Insufficiency

To investigate the network pharmacology of Shou Tai Pills in the treatment of premature ovarian insufficiency.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine(BATMAN-TCM) and GeneCards database were used to obtain the active ingredient and disease targets of Shou Tai Pills; Venn online tools were used to screen both intersection genes; relying on the STRING database,Cytoscape 3.7.0 software were used to build active ingredient-targets between network diagram and the target protein-protein interaction(PPI) network diagram; Gene ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed on the intersection genes by David database,and a network diagram of active ingredients-target-key pathway was constructed to demonstrate the relevant mechanism of Shou Tai Wan in the treatment of premature ovarian insufficiency.Results:A total of 21 active components,591 components targets and 2 438 disease targets were screened out,the main compounds were quercetin,lysine,etc.A total of 67 overlapping genes were obtained,suggesting that Shou Tai Wan may act through catalase(CAT),epidermal growth factor(EGF) and other targets.GO analysis results showed that the biological process of Shou Tai Wan was mainly drug reaction,the cell component was mainly heme binding reaction,and the molecular function was mainly concentrated in mitochondrial matrix.The major related signaling pathways involved are hypoxia inducible factor 1(HIF-1) signaling pathway and phosphatidylinositol 3 kinase/protein kinase B(PI3K-AKT) signaling pathway.Conclusion:A variety of active ingredients of Shou Tai Pills may act on CAT,EGF and other related targets,and play a role in the treatment of premature ovarian insufficiency through HIF-1,PI3K/AKT and other major signaling pathways.