目的:基于网络药理学与分子对接研究当归四逆汤治疗稳定型心绞痛(stable angina pectoris,SAP)的作用机制.方法:使用SyMmap数据库和中药系统药理学数据库与分析平台检索当归四逆汤组方中药甘草、大枣、当归、桂枝、细辛、通草和白芍的化学成分及相关靶点;在GeneCards数据库获取SAP相关疾病靶点;取SAP疾病相关靶点和当归四逆汤组方中药活性成分相关靶点的交集,即为当归四逆汤治疗SAP的潜在靶点,并绘制韦恩图.利用STRING 11.5 数据库对潜在靶点进行蛋白质相互作用(protein protein interaction,PPI)网络分析并筛选核心靶点.采用Cytoscape 3.10.1 构建"中药-活性成分-潜在靶点"网络,并筛选关键成分.采用Matascape对潜在靶点进行基因本体(Gene Ontology,GO)富集分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路富集分析.利用PyMOL4.6.0 对关键靶点和成分进行分子对接.结果:从当归四逆汤组方中药共筛选得到155 种化学成分及1 728 个相关靶点;在GeneCards数据库获得SAP相关靶点1 089个;取交集得到当归四逆汤治疗SAP的潜在靶点121 个.PPI网络分析发现信号传导及转录激活蛋白 3(signal transducer and activator of transcription 3,STAT3)、B细胞淋巴因子 2(B cell lymphoma 2,BCL2)、蛋白激酶B1(protein kinase B1,PKB1,又称AKT1)等为核心靶点;"中药-活性成分-潜在靶点"网络分析筛选出槲皮素、山柰酚、β-谷甾醇等为关键成分.GO分析得到4 688 个生物过程,404 个细胞组分和 715 个分子功能;KEGG分析得到磷脂酰肌醇 3-激酶(phosphoinositide 3-kinase,PI3K)-AKT、缺氧诱导因子 1(hypoxia-inducible factor 1,HIF1)、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)等200 条信号通路.分子对接显示活性成分与靶点对接良好.结论:当归四逆汤中的多个化学成分通过调控多个相关靶点参与多条信号通路发挥治疗SAP的作用.
Study on Action Mechanism of Chinese Angelica Frigid Extremities Decoction in Treating Stable Angina Pectoris Based on Network Pharmacology and Molecular Docking
Objective:To study on the action mechanism of Chinese Angelica Frigid Extremities Decoction in treating stable angina pecto-ris(SAP)based on network pharmacology and molecular docking.Methods:The chemical components of Chinese Angelica Frigid Ex-tremities Decoction,composed of Gancao(Radix Glycyrrhizae),Dazao(Fructus Jujubae),Danggui(Radix Angelicae Sinensis),Guizhi(Ramulus Cinnamomi),Xixin(Radix et Rhizoma Asari),Tongcao(Medulla Tetrapanacis)and Baishao(Radix Paeoniae Alba)were re-trieved from the SyMmap and TCMSP databases.Active ingredient-related targets were identified using the Metascape database.SAP-re-lated disease targets were collected from the GeneCards database.The intersection of SAP-related and active ingredient-related targets was identified as potential therapeutic targets,and a Venn diagram was generated.Protein-protein interaction(PPI)network analysis of potential targets was performed using STRING 11.5,and core targets were identified.A"Chinese medicinal-active ingredient-potential target"network was constructed using Cytoscape 3.10.1 to screen key compounds.Gene Ontology(GO)enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were conducted using Metascape.Molecular docking of key targets and ingredients was performed using PyMOL4.6.0.Results:A total of 155 chemical components and 1 728 related targets were i-dentified from Chinese Angelica Frigid Extremities Decoction.From the GeneCards database,1 089 SAP-related targets were obtained.The intersection yielded 121 potential therapeutic targets for SAP.PPI network analysis revealed interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and IL-1β,etc.as core targets.The"Chinese medicinal-active ingredient-potential target"network identified quer-cetin,kaempferol,and β-sitosterol,etc.as key components.GO analysis yielded 4 688 biological processes,404 cellular components,and 715 molecular functions.KEGG analysis identified200 signaling pathways,including phosphoinositide3-kinase(PI3K-AKT),hypoxia-inducible factor 1(HIF1),and mitogen-activated protein kinase(MAPK),etc.Molecular docking demonstrated strong binding affinity between active ingredients and core targets.Conclusion:Multiple chemical ingredients of Chinese Angelica Frigid Extremities Decoction dan regulate various targets and participate in multiple signaling pathways,contributing to its therapeutic effects on SAP.
Chinese Angelica Frigid Extremities Decoctionstable angina pectoris(SAP)network pharmacologymolecular dockingZhang zhongjingTreatise on Cold Damage Diseases
国家科技期刊平台
NSTL
万方数据
