摘要
目的:应用网络药理学与分子对接技术探讨祛湿化痰方治疗冠心病潜在的分子及生物通路机制。方法:采用中药系统药理学分析平台(TCMSP)数据库检索药物有效成分及作用靶点;检索GeneCards和OMIM数据库获得冠心病相关基因;使用Venny软件绘制韦恩图;利用Cytoscape软件及STRING数据库构建平台网络;使用R语言,分析京都基因和基因组百科全书(KEGG)通路富集以及基因本体(GO)生物过程;运用PubChem网站、PDB数据库寻找配体及受体结构,应用AutodockTools及Vina软件进行分子对接运算。结果:在祛湿化痰方核心药物中共筛选获得36个主要活性化合物、416个潜在作用靶点;7264个基因靶点与冠心病有关;祛湿化痰方与冠心病的交集蛋白靶点140个;核心基因蛋白靶点有7个,包括雌激素受体α(ESR1)、丝裂原活化蛋白激酶1(MAPK1)、JUN、丝裂原活化蛋白激酶3(MAPK3)、肿瘤蛋白p53(TP53)、蛋白激酶B1(AKT1)、丝裂原活化蛋白激酶14;GO生物过程富集分析显示(MAPK14),祛湿化痰方治疗冠心病与氧化应激反应、对营养水平的响应等有关,KEGG通路富集分析获得170条相关的信号通路,与雌激素信号通路及磷脂酰肌醇-3-激酶(PI3K)-蛋白激酶B(AKT)信号通路关联紧密;分子对接运算发现AKT1、ESR1与柚皮苷,MAPK14、MAPK3与汉黄芩素之间的结合能(≤-8.0 kJ/mol)较小,且具有稳定的分子构象。结论:祛湿化痰方中存在柚皮苷、汉黄芩素等多种小分子化合物,可以稳定结合ESR1、AKT1、MAPK1等多个基因受体,其作用的生物通路机制可能与雌激素信号通路及PI3K-AKT信号通路有关。
Objective:To explore the potential molecular mechanism and biological pathway of Qushi Huatan Prescription in the treatment of coronary heart disease(CHD)by network pharmacology and molecular docking technology.Methods:Traditional Chinese Medicines Systems Pharmacology Platform(TCMSP)database was used to search for active ingredients and targets of drugs.GeneCards and OMIM database were used to search potential gene targets of CHD.Venny software was used to draw Venn map.Cytoscape software and STRING database were used to build platform network.R language was used to compute the enrichment analysis for gene ontology(GO)biological process and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway.The structure of ligand and receptor were searched by PubChem website and PDB database.Molecular docking was calculated by AutoDockTools and Vina software.Results:There were 36 active compounds and 416 potential targets in Qushi Huatan Prescription.A total of 7264 gene targets which related to CHD and 140 intersection protein targets was found.There were 7 core gene protein targets,including estrogen receptorα(ESR1),mitogen activated protein kinase 1(MAPK1),JUN,mitogen activated protein kinase 3(MAPK3),tumor protein p53(TP53),protein kinase B1(AKT1),mitogen activated protein kinase 14(MAPK14).Enrichment analysis of GO biological process of Qushi Huatan Prescription in treating CHD showed that it was related to oxidative stress response and response to nutrient level.The KEGG pathway enrichment analysis showed that it was related to 170 signal pathways,and closely related to estrogen signaling pathway and phosphatidylinositol-3-kinase(PI3K)-AKT signaling pathway.Molecular docking found that naringin with ESR1 and AKT1,wogonin with MAPK3 and MAPK14 Showed stable molecular conformation,which binding energy were less than≤-8.0 kJ/mol.Conclusion:Small molecular compounds such as naringin and wogonin which would be found from Qushi Huatan Prescription could stably bind to multiple gene receptors,such as ESR1,AKT1,and MAPK1.The biological pathway mechanism of Qushi Huatan Prescription in the treatment of CHD maybe related to estrogen signaling pathway and PI3K-AKT signaling pathway.
作者
侯时昭
许文静
蓝涛华
吕渭辉
HOU Shizhao;XU Wenjing;LAN Taohua;LYU Weihui(The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine,Guangzhou 510370,Guangdong,China)
出处
《中西医结合心脑血管病杂志》
2023年第9期1543-1552,共10页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
省部共建中医湿证国家重点实验室开放课题资助项目(No.SZ2020ZZ21)
广州市科技局校(院)联合资助(登封医院)基础研究项目(No.202201020348)。
关键词
冠心病
祛湿化痰方
网络药理
分子对接
信号通路
coronary heart disease
Qushi Huatan Prescription
network pharmacology
molecular docking technology
signal pathway
