基于网络药理学探讨西洋参-丹参治疗冠心病的作用机制  

Mechanism of American Ginseng-Salvia Miltiorrhiza in Treatment of Coronary Heart Disease Based on Network Pharmacology

作　　者：林泉 徐凤芹[1] 马晓娟[1] 王哲 李丹丹[1,2] 殷惠军 LIN Quan;XU Fengqin;MA Xiaojuan;WANG Zhe;LI Dandan;YIN Huijun(Xiyuan Hospital of China Academy of Chinese Medical Sciences Beijing 100091,China,Graduate School of China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]中国中医科学院西苑医院,北京100091 [2]中国中医科学院研究生院,北京100700

出　　处：《中西医结合心脑血管病杂志》2021年第11期1777-1787,共11页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金项目(No.81173584)。

摘　　要：目的基于网络药理学方法分析西洋参-丹参药对治疗冠心病的分子机制。方法通过中药系统药理学数据库与分析平台(TCMSP)检索西洋参、丹参的活性成分及其靶点,并在Uniport数据库标准化蛋白质靶点信息;通过Gencards、OMIM、TTD、DRUGBANK数据库获取冠心病相关靶点基因,筛选药物和疾病共同靶点,利用CytoScape3.7.0软件构建“成分-靶点”网络,筛选关键活性成分;通过STRING平台进行蛋白质相互作用分析,构建共同靶点PPI网络,筛选关键靶点基因;采用DAVID数据库对共同靶点进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,通过CytoScape3.7.0软件构建“成分-靶点-通路”网络。结果共筛选得到西洋参-丹参63个活性成分和153个潜在靶点,与1420个冠心病靶点相映射,得到72个共同靶点,富集分析得到GO分析结果578个、信号通路116条;西洋参-丹参的关键活性成分木犀草素、丹参酮ⅡA、β-谷甾醇、4-亚甲丹参新酮、丹参新醌D、二氢丹参内酯、2-异丙基-8-甲基菲-3,4-二酮、罂粟碱、鼠尾草酚酮和隐丹参酮主要通过调控信号传导与转录激活因子3(STAT3)、蛋白激酶1(AKT1)、肿瘤抑制蛋白53(TP53)、肿瘤坏死因子(TNF)、丝裂原活化蛋白激酶1(MAPK1)、丝裂原活化蛋白激酶14(MAPK14)、白细胞介素6(IL6)、血管内皮生长因子A(VEGFA)、人原癌基因c-Fos(FOS)、白细胞介素1β(IL1B)等相关靶点蛋白,干预机体的细胞增殖凋亡、炎症反应、信号转导、缺氧反应、基因表达、药物反应、对雌二醇的反应、蛋白质磷酸化等生物学过程,并可能通过HIF-1信号通路、PI3K/Akt信号通路、TNF信号通路、FoxO信号通路、MAPK信号通路、雌激素信号通路、T细胞受体信号通路等对冠心病的发生发展产生影响。结论初步揭示了西洋参-丹参治疗冠心病多成分、多靶点、多通路的作用机制,为进一步临床开发利用提�Objective To analyze the molecular mechanism of American Ginseng-Salvia Miltiorrhiza in the treatment of coronary heart disease based on network pharmacology.Methods The active components and their targets of American Ginseng-Salvia Miltiorrhiza were retrieved by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the protein target information was standardized in Uniport database.The target genes related to coronary heart disease were obtained from GenCards,OMIM,TTD and DRUGBANK databases,and the common targets of drugs and diseases were screened using Cytoscape3.7.0 software to construct a"component-target"network to screen key active ingredients.Protein interaction analysis was performed through the String platform to construct a common target PPI network and screen key target genes.Genome ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed on common targets using David database,and"component-target-pathway"network was constructed by Cytoscape3.7.0 software.Results A total of 63 active components and 153 potential targets of American Ginseng-Salvia Miltiorrhiza were screened,which were mapped to 1,420 coronary heart disease targets,and 72 common targets were obtained.The enrichment analysis obtained 578 GO analysis results and 116 signal pathways.The results showed that luteolin,tanshinoneⅡA,β-sitosterol,4-methylene salvianone,dan-shexinkum D,dihydrotanshinlactone,2-isopropyl-8-methylphenanthrene-3,4-dione,papaverine,salviolone and cryptotanshinone were the key active components of American Ginseng-Salvia Miltiorrhiza.These active ingredients mainly regulated signal transduction and transcription activator 3(STAT3),protein kinase 1(AKT1),tumor suppressor protein 53(TP53),tumor necrosis factor(TNF),mitogen activated protein kinase 1(MAPK1),mitogen activated protein kinase 14(MAPK14),interleukin 6(IL6),vascular endothelial growth factor A(VEGFA),human proto-oncogene c-Fos(FOS),interleukin1β(IL1B)an

关 键 词：冠心病 西洋参 丹参 网络药理学 作用机制 

分 类 号：R28[医药卫生—中药学]