摘要
目的基于网络药理学研究槲皮素治疗冠心病的分子机制。方法通过TCMSP、Swiss Target Prediction和Pharm Mapper数据库,收集槲皮素的潜在靶点,使用DisGeNET和GeneCards数据库查询冠心病的相关靶点,通过构建Venn图,得到槲皮素-冠心病共同靶点。运用STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,Cytoscape 3.7.2软件的cytoHubba插件对PPI网络进行分析,得到槲皮素治疗冠心病的关键靶点。通过Metascape数据库对共同靶点进行GO和KEGG通路富集分析,并使用Auto Dock Vina软件进行分子对接。结果共得到233个槲皮素-冠心病共同靶点,筛选出5个核心靶点:丝氨酸/苏氨酸蛋白激酶1(AKT1)、肿瘤抑制蛋白P53(TP53)、丝裂原活化蛋白激酶1(MAPK1)、白介素-6(IL-6)、血管内皮生长因子A(VEGFA)。GO分析中,生物学过程主要与创伤反应、脂多糖反应、凋亡信号通路、有毒物质反应、细胞运动正调节相关。KEGG通路分析主要富集在癌症、糖尿病并发症AGE-RAGE信号通路、MAPK信号通路、HIF-1信号通路、铂耐药等。分子对接的平均对接亲和力为-7.9 kcal/mol,提示结合活性较好。结论槲皮素治疗冠心病的机制具有多靶点、多通路特点,为后续的基础研究提供了思路。
Objective To explore the molecular mechanism of quercetin in treating coronary heart disease based on network pharmacology and molecular docking technology.Methods Potential targets of quercetin were collected through TCMSP,Swiss Target Prediction and Pharm Mapper databases,relevant targets of coronary heart disease were investigated using DisGeNET and GeneCards databases,and the common Target of quercetin and coronary heart disease was obtained by constructing Venn diagram.Using STRING database to construct PPI network,cytoHubba plug-in of Cytoscape 3.7.2 software was used to analyze PPI network and obtain the key target of quercetin for coronary heart disease.Metascape database was used for enrichment analysis of GO and KEGG pathways for common targets,and Auto Dock Vina software was used for molecular docking.Results A total of 233 common targets of quercetin-coronary heart disease were obtained,and 5 core targets were screened:RAC-alpha serine/threonine-protein kinase 1(AKT1),cellular tumor antigen p53(TP53),mitogen-activated protein kinase 1(MAPK1),vascular endothelial growth factor A(VEGFA),interleukin-6(IL-6).In GO analysis,the biological process was mainly related to response to wounding,response to lipopolysaccharide,apoptotic signaling pathway,response to toxic substance and positive regulation of cell motility.KEGG pathway analysis was mainly enriched in:Pathways in cancer,Glycosylation End products(AGE)and their receptors(RAGE)signaling pathway in diabetic complications,MAPK signaling pathway,hypoxia induction factor-1 signaling pathway and platinum drug resistance.The average docking affinity of molecular docking was-7.9 kcal/mol,suggesting that the binding activity was better.Conclusion The mechanism of quercetin in treating coronary heart disease was characterized by multi-target and multi-pathway,which could provide insights for further experimental study.
作者
徐江林
林谦
刘静
万洁
崔晓云
纪翔
毛天诗
张卓
逯金金
XU Jianglin;LIN Qian;LIU Jing;WAN Jie;CUI Xiaoyun;JI Xiang;MAO Tianshi;ZHANG Zhuo;LU Jinjin(Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100070,China)
出处
《中西医结合心脑血管病杂志》
2020年第24期4097-4103,共7页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
北京市科学技术委员会首都临床特色应用研究专项资助课题(No.Z181100001718064)
北京中医药大学基本科研业务费项目(科研创新团队项目)
中央高校基本科研业务费专项资金资助(No.2019-JYB-TD008)。
关键词
冠心病
槲皮素
网络药理学
分子对接
coronary heart disease
quercetin
network pharmacology
molecular docking technology
