摘要
目的运用网络药理学与分子对接技术探讨冠心舒通胶囊治疗心力衰竭的作用机制。方法通过TCMIP及TCMSP数据库筛选冠心舒通胶囊的活性成分及其作用靶点,通过GeneCard、OMIM、TTD等数据库筛选心力衰竭的疾病相关靶点;获取活性成分作用靶点与疾病相关靶点的交集靶点(共同靶点),即冠心舒通胶囊治疗心力衰竭的潜在作用靶点。使用Cytoscape 3.7.2软件构建“活性成分-潜在作用靶点”网络,并分析网络中的核心活性成分;将交集靶点导入STRING数据库进行蛋白互作(PPI)网络分析,筛选出潜在核心靶点;运用Metascape平台对潜在核心靶点进行GO功能及KEGG通路富集分析;利用AutoDock Tools 1.5.6软件对核心成分、靶点进行分子对接。结果共筛选得到83个活性成分及173个潜在作用靶点;获得槲皮素、山柰酚、积雪草酸、柚皮素、丹参酮ⅡA等核心活性成分,FOS、TP53、STAT3、MAPK3、JUN、MAPK14、MAPK1和AKT1等核心靶点;共筛选得到92条信号通路,关键通路包括MAPK信号通路、AGE-RAGE信号通路、Toll样受体信号通路、TNF信号通路、细胞凋亡等。所有分子对接结果的最小结合能均<-5.0 kJ·mol^(-1),表明对接良好。结论冠心舒通胶囊可能是通过槲皮素、山柰酚、丹参酮ⅡA等关键活性成分,作用于FOS、TP53、MAPK3等潜在核心靶点,调控MAPK、AGE-RAGE、Toll样受体等信号通路,从而发挥治疗心力衰竭的作用。
Objective To investigate the mechanism of Guanxin Shutong Capsules in the treatment of heart failure(HF)using network pharmacology and molecular docking techniques.Methods The active ingredients of Guanxin Shutong Capsules and their targets were screened by TCMIP and TCMSP databases,and the disease-related targets of HF were screened by GeneCard,OMIM and TTD databases to obtain the intersecting targets(common targets),namely the potential targets of Guanxin Shutong Capsules for the treatment of HF.Cytoscape 3.7.2 software was used to construct the network of“active components-potential targets”and analyze the core active components in the network;the intersection targets were imported into STRING database for protein-protein interaction(PPI)network analysis,and potential core targets were screened out;Metascape platform was used to analyze GO function and KEGG pathway enrichment;AutoDockTools 1.5.6 software was used for molecular docking of core components and targets.Results A total of 83 active ingredients and 173 potential targets were screened;core active compounds such as quercetin,kaempferol,asiatic acid,naringenin and tanshinoneⅡA,and core targets such as FOS,TP53,STAT3,MAPK3,JUN,MAPK14,MAPK1 and AKT1 were obtained;a total of 92 signaling pathways were screened,including MAPK signaling pathway,Toll-like receptor signaling pathway,TNF signaling pathway and apoptosis.The key pathways included MAPK signaling pathway,AGE-RAGE signaling pathway,Toll-like receptor signaling pathway,TNF signaling pathway,apoptosis.The minimum binding energy of all molecules was<-5.0 kJ·mol^(-1),indicating good docking.Conclusion Guanxin Shutong Capsules may act on potential core targets such as FOS,TP53 and MAPK3 through key active ingredients such as quercetin,kaempferol and tanshinoneⅡA to modulate MAPK,AGE-RAGE,Toll-like receptors and other signalling pathways for the treatment of HF.
作者
申海亮
杜海霞
周惠芬
徐嘉平
张玲
何昱
杨洁红
万海同
SHEN Hailiang;DU Haixia;ZHOU Huifen;XU Jiaping;ZHANG Ling;HE Yu;YANG Jiehong;WANHaitong(School of Basic Medical Science,Zhejiang Chinese Medical University,Hangzhou 310053 Zhejiang,China;School of Life Science,Zhejiang Chinese Medical University,Hangzhou 310053 Zhejiang,China;School of Pharmaceutical Science,Zhejiang Chinese Medical University,Hangzhou 310053 Zhejiang,China)
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2022年第8期1093-1101,共9页
Traditional Chinese Drug Research and Clinical Pharmacology
基金
国家重点研发计划项目(2017YFC1700400,2017YFC1700403)
国家重点研发计划中医药现代化研究重点专项(2018YFC1704200,2018YFC1704204)
浙江省“万人计划”杰出人才项目(2019R51002)
浙江省中医脑病重点实验室项目(2020E10012)。
关键词
冠心舒通胶囊
心力衰竭
网络药理学
槲皮素
山柰酚
MAPK
分子对接
Guanxin Shutong Capsules
heart failure(HF)
network pharmacology
quercetin
kaempferol
MAPK
molecular docking
