摘要
目的:应用网络药理学及分子对接技术探讨麝香干预阿霉素心脏毒性(adriamycin-induced cardiotoxicity, AIC)的作用机制。方法:利用TCMSP和Herb数据库检索经ADMETlab筛选得到麝香有效成分和作用靶点,利用转录组数据分析得到AIC靶点,将麝香作用靶点与AIC相关靶点取交集,得到麝香干预AIC的潜在靶点。然后采用STRING数据库构建蛋白质相互作用网络,导入Cytoscape软件构建“麝香-有效成分-靶点-AIC”网络,并进行网络拓扑学分析得到核心靶基因。利用Hiplot在线软件对靶点基因进行GO功能和KEGG通路富集分析。运用CB-Dock在线工具对核心靶点和有效成分进行分子对接。结果:筛选得到麝香有效成分4个,分析得到AIC相关靶点3404个。构建“麝香-有效成分-靶点-AIC”网络后经网络拓扑学分析显示CHRNA7与PGR为麝香干预AIC潜在核心靶点。GO富集分析显示麝香干预AIC涉及的分子功能及生物学过程共97个,包括regulation of membrane potential、neurotransmitter receptor activity、acetylcholine receptor signaling pathway、GABA-A receptor activity等。KEGG富集分析显示麝香干预AIC的相关信号通路6条,包括Neuroactive ligandreceptor interaction、Cholinergic synapse、GABAergic synapse等。分子对接的结果显示,麝香的三种主要有效成分桑黄素、N-去甲荷叶碱、胆固醇均与CHRNA7及PGR有较好的结合能力。结论:麝香可通过多靶点、多通路干预AIC,将为进一步深入研究麝香干预AIC的作用奠定基础。
Objective To investigate the mechanism of musk against adriamycin-induced cardiotoxicity(AIC)through net⁃work pharmacology and molecular docking.Methods TCMSP and Herb databases were used to retrieve the effective compo⁃nents and targets of musk through ADMETlab screening,and the AIC targets were obtained by transcriptome data analysis.The potential targets for musk to interfere with AIC were obtained by intersecting the musk targets and AIC-related targets.Then,the STRING database was used to construct the protein interaction network,and the Cytoscape software was imported to construct the"musk-active ingredient-target-AIC"network,and the core target genes were obtained by network topolo⁃gy analysis.The GO function and KEGG pathway enrichment analysis of target genes were performed using Hip-lot online software.Use the CB-Dock online tool to carry out molecular docking on the core target and active ingredients.Results Four active ingredients of musk were screened,and 3404 AIC-related targets were analyzed.After constructing the"musk-active ingredient-target-AIC"network,network topology analysis showed that CHRNA7 and PGR were potential core targets for musk intervention on AIC.GO enrichment analysis showed that musk interfered with AIC involving 97 molecular functions and biological processes,including regulation of membrane potential,neurotransmitter receptor activity,acetyl⁃choline receptor signaling pathway,GABA A receptor activity,etc.KEGG enrichment analysis showed that musk interfered with 6 related signaling pathways of AIC,including neuroactive ligand receptor interaction,Cho-linergic synapse,GABAergic synapse,etc.The results of molecular docking showed that the three main active ingredients of musk,morin,N-nornuciferine and cholesterol,all had good binding abilities to CHRNA7 and PGR.Conclusion Musk may treat AIC through multi-targets and multi-pathways,which lays the foundation for further in-depth study on the mechanism of action of musk in interfering with AIC.
作者
潘奕君
薛翔月
王广立
陈梦瑶
谢琳
万国兴
PAN Yi-jun;XUE Xiang-yue;WANG Guang-li;CHEN Meng-yao;XIE Lin;WAN Guo-xing(The Third Clinical Medical School,Hubei University of Medicine,Shiyan,Hubei 442000,China;The Third Clinical Medical School,Institute of Medicine and Nursing,Hubei University of Medicine,Shiyan,Hubei 442000,China;Renmin Hospital,Hubei University of Medicine,Shiyan,Hubei 442000,China)
出处
《湖北医药学院学报》
CAS
2023年第3期235-242,共8页
Journal of Hubei University of Medicine
基金
国家自然科学基金项目(82204540)
湖北省自然科学基金项目(2020CFB158)
国家级大学生创新创业训练计划项目(202213249002)
湖北省教育厅青年人才项目(Q20222111)。
关键词
麝香
阿霉素心脏毒性
网络药理学
分子对接
Musk
Adriamycin-induced cardiotoxicity
Network pharmacology
Molecular docking
