基于网络药理学研究丹参-红花治疗冠心病的物质基础及作用机制

Material Basis and Molecular Mechanism of Herbal Pair Danshen-Honghua Against Coronary Heart Disease Based on Network Pharmacology

目的:基于网络药理学探讨丹参-红花治疗冠心病(CHD)的物质基础和作用机制。方法:借助中药系统药理学数据库与分析平台(TCMSP)检索中药丹参、红花的化学成分,根据口服生物利用度和类药性筛选化学成分,通过PubChem、PharmMapper在线数据库预测化学成分的靶点,检索DisGeNET在线数据库获取CHD的相关靶点,利用Venny 2.1软件获得药物-疾病之间的共同靶点,在STRING 10.5数据库中导入共同靶点并进行蛋白质-蛋白质相互作用(PPI)网络分析,使用Cytoscape 3.7.1软件构建药物-成分-靶点-疾病网络,最后通过DAVID 6.8在线数据库进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)富集分析。结果:从丹参-红花中筛选得到13个关键成分,10个核心靶点;通过GO分析得到292个生物过程(BP),25个细胞组分(CC),和62个分子功能(MF);通过KEGG分析得出富集通路115条。槲皮素、木犀草素、山柰酚、丹参酮Ⅱa、黄芩苷等成分可能是丹参-红花治疗CHD的核心成分;IL6、AKT1、VEGFA、CXCL8、PTGS2、IL1B、NOS3、CCL2、MMP9等为核心靶点;流体剪切应力与动脉粥样硬化通路、HIF-1信号通路、IL-17信号通路、TNF信号通路、松弛素信号通路等为关键通路。结论:丹参-红花通过调节冠状动脉粥样硬化进程、减轻血管炎症反应、扩张冠状动脉、抗血栓形成、减轻心肌缺血缺氧损伤,从而发挥治疗CHD的作用。

Objective:To explore the material basis and molecular mechanism of Danshen(Salviae Miltiorrhizae Radix et Rhizoma) combined with Honghua(Carthami Flos) against coronary heart disease(CHD) based on network pharmacology.Methods:The active compounds of Danshen-Honghua(DS-HH) were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and screened out according to oral bioavailability and drug-likeness.The targets of chemical compounds were predicted by PubChem and PharmMapper, and related targets of CHD were retrieved from DisGeNET.The common targets of CHD and DS-HH were obtained by Venny 2.1 and imported into STRING 10.5 for protein-protein interaction(PPI) network analysis.The drug-component-target-disease network was constructed by Cytoscape 3.7.1.Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway analyses were performed by DAVID 6.8.Results:Thirteen key chemical compounds and 10 key targets were screened out from DS-HH.A total of 292 biological processes(BP),25 cellular components(CC),and 62 molecular functions(MF) were obtained by GO analysis.KEGG analysis yielded 115 enrichment pathways.Quercetin, luteolin, kaempferol, tanshinone Ⅱa, and baicalin might be the core compounds of DS-HH against CHD.IL6,AKT1,VEGFA,CXCL8,PTGS2,IL1 B,NOS3,CCL2,and MMP9 might be the key targets.The fluid shear stress and atherosclerosis pathway, HIF-1 signaling pathway, IL-17 signaling pathway, TNF signaling pathway, and relaxin signaling pathway might be the core signaling pathways.Conclusion:DS-HH played a role in the treatment of CHD by regulating the process of coronary atherosclerosis, reducing vascular inflammation, dilating coronary arteries, preventing thrombosis, and relieving myocardial ischemia and hypoxia injury.