摘要
目的:基于网络药理学方法结合分子对接技术探讨冠心苏合丸(GXSHW)干预冠心病(coronary heart disease,CHD)的生物活性成分、关键靶点和潜在药理作用机制。方法:利用BATMAN-TCM数据库在线分析工具,获取GXSHW中每味中药的化合物成分和作用靶点,并进行筛选。通过GeneCards在线数据库获得CHD的相关靶点,利用Venny 2.1.0得到GXSHW与CHD的交集靶点。在STRING 11.5数据库中导入交集靶点并进行蛋白质-蛋白质相互作用(PPI)网络分析,使用Cytoscape 3.9.1软件构建药物-成分-靶点网络,并通过拓扑分析筛选GXSHW治疗CHD排名前10位的核心靶点。之后通过DAVID在线数据库进行基因本体(GO)功能富集分析,包括生物过程(BP)、细胞组分(CC)、分子功能(MF)及KEGG通路富集分析,导出数据利用微生信在线软件作图展示。通过Autodock Tools 1.5.6软件对核心有效成分以及核心靶点进行分子对接验证。结果:从GXSHW筛选得到17个治疗CHD的核心成分,包括月桂酸、油酸、苏合香酯等;核心靶点有ADH1C、NR3C1、PIK3CA等。通过GO功能分析得到282个生物过程(BP)、62个细胞组分(CC)和68个分子功能(MF)。通过KEGG通路富集分析得到62条通路,其中糖尿病性心肌病、cGMP-PKG信号通路、流体剪切应力与动脉粥样硬化、心肌细胞的肾上腺素能信号传导、中性粒细胞胞外陷阱形成、白细胞经内皮细胞迁移、脂肪细胞中脂肪分解的调节、脂质和动脉粥样硬化、肾素分泌、破骨细胞分化、促性腺激素分泌、醛固酮调节的钠重吸收、钙信号通路、NF-κB信号通路等为GXSHW治疗CHD的核心通路。运用分子对接技术验证GXSHW中粉防己碱、油酸、α-枯烯、白桦脂酸与ADH1C、NR3C1、PIK3CA的结合能<-5.0 kcal/mol,对接效果好。结论:冠心苏合丸通过抑制血小板聚集、改善血管内皮功能、防止血栓形成、抑制血管平滑肌增殖、稳定粥样斑块等作用治疗冠心病。GXSHW�
Objective:To explore the bioactive components,key targets and potential pharmacological mechanisms of Guanxin Suhe Pill(GXSHP)in the intervention of coronary heart disease(CHD)based on network pharmacology method and molecular docking technology.Methods:The BATMAN-TCM database online analysis tool was used to obtain and screen the compound components and action targets of each Chinese medicine in GXSHP.The related targets of CHD were obtained through GeneCards online database,and the intersection targets of GXSHP and CHD were obtained by Venny 2.1.0.The intersection targets were imported into the STRING 11.5 database and protein-protein interaction(PPI)network analysis was performed.Cytoscape 3.9.1 software was used to construct the drug-component-target network and topological analysis was used to screen the top 10 core targets of GXSHP in the treatment of CHD.Then,the DAVID online database was used for gene ontology(GO)functional enrichment analysis,including biological process(BP),cellular component(CC),molecular function(MF),and KEGG enrichment pathway analysis.The exported data were displayed by using bioinformatics online software.Autodock Tools 1.5.6 software was used to verify the molecular docking of the core effective components and core targets.Results:17 core components for the treatment of CHD were screened from GXSHP,including lauric acid,oleic acid,and styracin.The core targets included ADH1C,NR3C1,PIK3CA,etc.GO functional analysis yielded 282 biological processes(BP),62 cellular components(CC),and 68 molecular functions(MF).62 pathways were obtained by enrichment analysis of KEGG pathways.Among them,diabetic cardiomyopathy,cGMP-PKG signaling pathway,fluid shear stress and atherosclerosis,adrenergic signaling in cardiomyocytes,neutrophil extracellular trap formation,leukocyte migration through endothelial cells,regulation of lipolysis in adipocytes,lipid and atherosclerosis,renin secretion,osteoclast differentiation,gonadotropin secretion,sodium reabsorption regulated by aldosterone,calcium signali
作者
刘剑锋
况春燕
郭慧
Liu Jianfeng;Kuang Chunyan;Guo Hui(Guizhou University of Traditional Chinese Medicine,Guiyang Guizhou 550025;Department of Cardiology,Guizhou Provincial People′s Hospital,Guiyang Guizhou 550003;Liaoning University of Traditional Chinese Medicine,Shenyang Liaoning 110032)
出处
《山西中医药大学学报》
2023年第5期547-554,共8页
Journal of Shanxi University of Chinese Medicine
基金
国家自然科学基金项目(81560056)
贵州省第十二批优秀青年科技人才项目(黔科合平台人才[2019]5662)
贵州省科技计划项目(黔科合基础[2018]1097)
贵州省留学人员科技活动择优资助项目(黔人项目资助合同[2018]0003号)
贵州省科技平台及人才团队计划项目(黔科合平台人才2017-5405)。
