基于网络药理学探讨黄芪、丹参治疗冠状动脉痉挛的活性成分与分子机制

The Active Components and Molecular Mechanism of Huangqi and Danshen in the Treatment of Coronary Artery Spasm Based on Network Pharmacology

目的基于网络药理学探讨黄芪、丹参治疗冠状动脉痉挛的活性成分与分子机制。方法通过中药系统药理学数据库与分析平台(TCMSP)筛选出黄芪、丹参有效成分及相关靶点,将结果导入CytoScape 3.8.2绘制药物-有效成分-靶点网络图,使用其内置Network Analyzer工具对节点的网络拓扑参数分析并筛选出主要有效成分;通过基因名片(GeneCards)数据库筛选冠状动脉痉挛相关靶点并于在线人类孟德尔遗传数据库(OMIM)、DRUGBANK数据库中检索相关靶点予以补充;通过在线工具构建Venn图并得到黄芪、丹参-冠状动脉痉挛交集靶点,将靶点导入STRING平台构建PPI网络,得到的网络模型通过CytoScape 3.8.2进一步处理得到最终网络模型,使用其内置Network Analyzer工具对节点的网络拓扑参数筛选出主要作用靶点;通过Metascape数据库对主要作用靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析;使用AutoDock Vina对主要有效成分及核心靶点进行分子对接验证。结果黄芪、丹参治疗冠状动脉痉挛的主要有效成分为槲皮素、山奈酚、木犀草素等;核心靶点为蛋白激酶B1(AKT1)、肿瘤抑制蛋白p53(TP53)、白细胞介素6(IL6)等;涉及的主要通路为晚期糖基化终末产物(AGE)-糖基化终末产物受体(RAGE)信号通路及流体剪切应力与动脉粥样硬化通路等。分子对接验证中平均对接亲和力为-32.604 kJ/mol。结论黄芪、丹参治疗冠状动脉痉挛的作用机制具有多成分、多靶点、多通路的特点,为之后基础研究提供了方向。

Objective To explore the active components and molecular mechanism of Huangqi and Danshen in the treatment of coronary artery spasm based on network pharmacology.Methods The active components and related targets of Huangqi and Danshen were screened out through the traditional Chinese medicine(TCM)systematic pharmacology database and analysis platform(TCMSP),and the results were imported into CytoScape 3.8.2 to draw the drug-active ingredient-target network diagram.The Network Analyzer tool is used to analyze the network topology parameters of nodes and screen out the main active components.The targets related to coronary artery spasm were screened by GeneCards database and retrieved in OMIM and DRUGBANK database to supplement them.Online tools were used to construct Venn diagrams and to obtain the junction targets of Huangqi,Danshen-coronary artery spasm.The targets were imported into the STRING platform to construct PPI network.The network model obtained was further processed by CytoScape 3.8.2 to obtain the final network model.The built-in Network Analyzer tool was used to screen out the main targets of the network topology parameters of nodes.Major targets were analyzed by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis through Metascape database.The main active components and core targets were verified by molecular docking using AutoDock Vina.Results The main active components of Huangqi and Danshen in the treatment of coronary artery spasm were quercetin,kaempferol,luteolin,etc.The core targets were protein kinase B1(AKT1),tumor suppressor protein p53(TP53),interleukin-6(IL6),etc.The main pathways involved were AGE-RAGE signaling pathway,fluid shear stress and atherosclerosis pathway,etc.The average docking affinity was-32.604 kJ/mol in molecular docking validation.Conclusion The mechanism of action of Huangqi and Danshen in the treatment of coronary artery spasm possesses the characteristics of multi-component,multi-target and multi-pathway,which provides direction guidance for future basic research.