基于网络药理学和分子对接探讨免怀散治疗高泌乳素血症的作用机制

The action mechanism of Mianhuai San on hyperprolactinemia based on network pharmacology and molecular docking

目的:采用网络药理学和分子对接技术预测免怀散治疗高泌乳素血症(Hyperprolactinemia,HPRL)的作用靶点,并探讨其治疗HPRL的潜在作用机制和有效物质。方法:通过数据库获取免怀散的潜在活性成分及其药物靶点,并且以“Hyperprolactinemia”为关键词在数据库中获取疾病靶点,通过Venny 2.1得到药物和疾病的共同靶点,从而构建中药有效成分靶点-疾病靶点网络。使用STRING数据库构建核心基因蛋白质-蛋白质相互作用网络。在Metascap数据库进行疾病与药物交集靶点的基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。最后通过“Autodock”软件对核心活性成分和核心靶点进行分子对接验证。结果:筛选得到免怀散的有效成分27个、核心靶点176个及疾病靶点228个,GO功能富集分析显示交集靶点参与了生物过程、细胞组分、分子功能等共715个生物功能条目;KEGG通路富集分析收集到113条通路,主要包括癌症通路、化学致癌作用-受体激活、酪氨酸蛋白激酶(Janus-activated Kinase,JAK)-信号转导和转录激活因子(Signal Transducer and Activator of Transcription,STAT)信号通路、癌症中的蛋白聚糖、乳腺癌、磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)信号通路、T细胞受体信号通路等。分子对接的结合能均小于-5 kcal/mol,分子对接结果良好。结论:免怀散可通过多成分、多靶点、多通路发挥治疗HPRL的作用,为临床应用免怀散治疗HPRL提供了一定的理论依据。

Objective:To predict the action targets of Mianhuai San(免怀散)in the treatment of hyperprolactinemia(HPRL)by network pharmacology and molecular docking technology,and explore the potential action mechanism and effective substances in the treatment of HPRL.Methods:The potential active ingredients and drug targets of Mianhuai San were obtained from the databases,and the disease targets were obtained from the databases with hyperprolactinemia as the keyword.The common targets of drugs and diseases were obtained by Venny 2.1,so as to construct the Chinese medicine active ingredient target-disease target network.The protein-protein interaction network of the core genes was performed by the STRING database.The intersecting targets of the disease and the drug were analyzed in the Metascape database for GO functional enrichment and KEGG pathway enrichment analyses.Finally,the molecular docking of the core active components and core targets was verified by the Autodock software.Results:There were 27 active ingredients and 176 core targets of Mianhuai San,and 228 disease targets in the screening.The GO functional enrichment analysis showed that the intersecting targets were involved in a total of 715 biological function items,including biological process items,cell component items,and molecular function items.KEGG pathway enrichment analysis collected 113 pathways,mainly including cancer pathway,chemical carcinogenesis-receptor activation,JAK-STAT signaling pathway,proteoglycans in cancer,breast cancer,PI3K-Akt signaling pathway,T-cell receptor signaling pathway and so on.The binding energies of molecular docking were all less than-5 kJ/mol,indicating that the molecular docking results were good.Conclusion:Mianhuai San can exert its therapeutic effect on HPRL through multi-component,multi-target and multi-pathway,and this conclusion provides some theoretical basis for the clinical application of Mianhuai San in the treatment of HPRL.