摘要
目的基于网络药理学、分子对接探讨藏药鬼箭锦鸡儿治疗高原红细胞增多症(high altitude polycythemia,HAPC)的分子机制。方法通过文献检索寻找鬼箭锦鸡儿的活性成分,采用SwissTargetPrediction数据库预测其潜在靶点,采用OMIM和GeneCards数据库筛选HAPC靶点,并将药物作用靶点和疾病靶点取交集,构建蛋白质互作网络(protein-protein interaction networks,PPI networks),借助DAVID数据库进行基因功能和通路富集分析,并采用AutoDock软件对关键活性成分和核心靶点进行分子对接,筛选鬼箭锦鸡儿活性成分潜在的作用靶点及相关信号通路。结果得到鬼箭锦鸡儿的有效活性成分25种,成分对应的靶点401个。连接度最高的前8种化学成分为7,3',4'-Trihgdroxy flavone、Geraldone、Quercetin、biochanin A、lsorhamnetin、7,4'-Dihydroxyflavone、Formononetin、Afrormosin。HAPC的疾病靶点共261个;药物成分与HAPC的交集靶点共41个,作用核心靶点包含VEGFA、AKT1、TNF、HAP90AA1、ESR1、MMP9、ACE、F2、CYP3A4、REN;参与的生物过程、细胞复合物、分子功能主要有缺氧反应生物过程、蛋白质磷酸化正调控过程、细胞表面、大分子复合体、类固醇结合、酶结合等;关键信号通路主要涉及Pathways in cancer、Chemical carcinogenesis-receptor activation、Fluid shear stress and atherosclerosis等。分子对接结果显示,8种主要活性成分与ACE、CYP3A4的结合情况很好,结合能均小于-8.5 kcal·mol^(-1)。结论鬼箭锦鸡儿的活性成分可以通过多通路作用于多靶点来治疗HAPC,为基础实验研究和临床应用提供一定的科学依据。
Objective To explore the molecular mechanism of the therapeutic effect of Tibetan medicine Caragana jubabt Poir on high altitude polycythemia(HAPC)based on network pharmacology and molecular docking.Methods The active ingredients of Caragana jubabt Poir were identified through literature review.The SwissTargetPrediction database was used to predict its potential targets.The OMIM and GeneCards databases were used to screen for HAPC targets.The drug action targets and disease targets were intersected to construct a protein-protein interaction network.The DAVID database was used for gene function and pathway enrichment analysis,and AutoDock software was used to perform molecular docking on key active ingredients and core targets,in order to screen out potential targets of action and related signaling pathways for the active ingredients of Caragana jubabt Poir.Results There were 25 effective active ingredients of Caragana jubabt Poir,with 401 corresponding targets.The top 8 components with the higher connectivity were 7,3',4'-Trihgdroxy flavone,Geraldone,Quercetin,biochanin A,lsorhamnetin,7,4'-Dihydroxyflavone,Formononetin,Afrormosin.261 HAPC targets were obtained and there was a total of 41 intersection targets between drug components and HAPC,the core targets including VEGFA,AKT1,TNF,HAP90AA1,ESR1,MMP9,ACE,F2,CYP3A4,REN;Biological process(BP),celluar components(CC),molecular function(MF)were mainly related with response to hypoxia,positive regulation of protein phorylation,cell surface,macromolecular complex,steroid binding,enzyme binding.The key signaling pathways mainly involved Pathways in cancer,Chemical carcinogenesis-receptor activation,Fluid shear stress and atherosclerosis,etc.The molecular docking results showed that the 8 main active ingredients had good binding with ACE and CYP3A4,and the binding energies were all less than-8.5 kcal·mol^(-1).Conclusion The active ingredients of Caragana jubabt Poir could act on multiple targets through multiple pathways to treat HAPC,which provides a certain scientific
作者
刘超
韩春笋
于进帅
李涛
陈帆
任建委
LIU Chao;HAN Chunsun;YU Jinshuai;LI Tao;CHEN Fan;REN Jianwei(School of Medicine,Tibet University,Lhasa 850000,China)
出处
《数理医药学杂志》
CAS
2024年第7期500-508,共9页
Journal of Mathematical Medicine
基金
西藏自治区自然科学基金一般项目(XZ202401ZR0010)。
关键词
鬼箭锦鸡儿
高原红细胞增多症
分子机制
网络药理学
分子对接
Caragana jubabt Poir
High altitude polycythemia
Molecular mechanism
Network pharmacology
Molecular docking
