基于网络药理学方法探讨芍药甘草汤治疗高催乳素血症的潜在作用机制

Potential Mechanism of Shaoyao Gancao Decoction in the Treatment of Hyperprolactinemia Based on Network Pharmacology

目的:基于网络药理学方法,探讨芍药甘草汤治疗高催乳素血症(HPRL)的作用机制。方法:通过中药系统药理学数据库与分析平台筛选白芍、甘草的主要活性成分及作用靶点;使用GeneCards数据库、DisGeNET数据库、人类孟德尔遗传综合数据库和Drugbank数据库收集HPRL相关靶点;利用Venny 2.1在线工具绘制韦恩图;使用STRING数据库进行蛋白质-蛋白质相互作用(PPI)分析,创建PPI网络;采用Cytoscape 3.7.1软件构建“药物-成分-靶点-疾病”网络;对潜在靶点在DAVID数据库中进行京都基因与基因组百科全书(KEGG)通路富集分析和基因本体(GO)功能富集分析。通过Autodock软件对主要活性成分和核心靶点进行分子对接验证。结果:筛选得到芍药甘草汤活性成分102个,与治疗HPRL相关的活性成分主要为槲皮素、山柰酚和芒柄花黄素等;取交集得到芍药甘草汤与HPRL相关靶点35个,其中核心靶点主要有雌激素受体1、α_(1B)-肾上腺素受体和血管内皮生长因子受体2等;GO功能富集分析到122个生物学过程,主要涉及一氧化氮生物合成过程的正调控、对乙醇的反应等;KEGG通路富集分析发现40条相关信号通路,主要为FoxO、缺氧诱导因子1、催乳素信号通路、JAK激酶-信号转导与转录激活子、磷脂酰肌醇3激酶-蛋白激酶B和丝裂原激活的蛋白激酶等信号通路。分子对接结果显示,主要活性成分与核心靶点具有较好的结合能力。结论:本研究初步揭示了芍药甘草汤治疗HPRL的多成分、多靶点和多通路作用机制,为更深一步的临床研究提供了理论基础。

OBJECTIVE:To explore the mechanism of Shaoyao Gancao decoction in the treatment of hyperprolactinemia(HPRL)based on network pharmacology.METHODS:The main active ingredients and targets of radix paeoniae alba and licorice were screened by traditional Chinese medicine systems pharmacology database and analysis platform.GeneCards,DisGeNET,Online Mendelian Inheritance in Man and Drugbank databases were used to predict the related targets of HPRL.Venny 2.1 online tool was used to draw Venn diagram.Protein-protein interaction(PPI)network was created by using STRING database for PPI analysis.Cytoscape 3.7.1 software was used to construct“drug-ingredient-target-disease”network.Potential targets were analyzed by Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis and gene ontology(GO)functional enrichment analysis in DAVID database.Molecular docking verification of main active ingredients and core targets was carried out by Autodock.RESULTS:A total of 102 active ingredients were obtained,and the main active ingredients related to HPRL were quercetin,kaempferol and formononetin.Totally 35 targets related to Shaoyao Gancao decoction and HPRL were obtained by the intersection,the core targets mainly included ESR1,ADRA1B and KDR,etc.GO functional enrichment analysis revealed 122 biological processes,mainly related to the positive regulation of nitric oxide biosynthetic process,and the response to ethanol.Enrichment analysis of KEGG pathway found 40 pathways,mainly FoxO,hypoxia inducible factor-1,prolactin signaling pathway,Janus kinase/signal transduction and transcription activator,phosphatidylinositol-3-kinase/protein kinase B,and mitogen-activated protein kinases and other signaling pathways.Molecular docking showed that the main active ingredients had good binding ability to the core target.CONCLUSIONS:This study preliminarily reveals the mechanism of multi-ingredient,multi-target and multi-path mechanism of Shaoyao Gancao decoction in the treatment of HPRL,which provides theoretical basis for further experimental research.