目的:运用网络药理学分析方法探究黄芪治疗糖尿病合并冠心病的可能性作用靶点以及其作用机制.方法:借助TCMSP平台及Uniprot数据库检索筛选黄芪的活性成分及其相应靶点;在GeneCards数据库、OMIM数据库中检索糖尿病合并冠心病的疾病靶点,通过Cytoscape 3.9.1 得到黄芪-活性成分-靶基因的可视化网络图;将疾病与药物对应靶点共同提交Venny2.1.0 生成相交靶点,并通过蛋白质相互作用(STRING)平台构建蛋白质相互作用(PPI)网络.基于Metascape 3.9.1 数据库进行GO富集分析和KEGG通路富集分析明确可能涉及到的生物进程及信号通路.最后应用分子对接技术对上述猜想进行粗浅验证.结果:共获取黄芪的关键化合物 17 个,对应靶点 195 个,疾病相关靶点 3815 个,导入Venny2.1.0 中生成 163 个交集靶点.富集分析结果表明:黄芪治疗糖尿病合并冠心病主要涉及激素反应(response to hormone)、细胞有机循环化合物反应(cellular response to organic cyclic compound)、细胞脂质反应(cellular response to lipid)、无机物反应(response to inorganic substance)等生物进程;可能涉及到癌症通路(Pathways in cancer)、脂质及动脉硬化通路(Lipid and atheroscierosis)、糖尿病并发症中的AGE-RAGE信号通路(AGE-RAGE signaling pathway in diabetic complications)、P13K-AKT信号通路(P13K-AKt signaling pathway)等信号通路.分子对接结果提示药物活性分子与核心靶点有较好的结合.结论:该研究揭示了黄芪在机体内可能参与抑制胰岛素抵抗、糖脂代谢调控等众多生物进程,以多成分、多靶点、多通路实现对糖尿病合并冠心病的治疗作用.
Study on the Mechanism of Astragalus in Treating diabetes Complicated with Coronary Heart Disease Based on Network Pharmacology and Molecular Docking
Objective:Use network pharmacology analysis method to explore the possible targets and mechanisms of Astragalus in treating diabetes complicated with coronary heart disease.Methods:Use the TCMSP platform and Uni-prot database to search and screen the active ingredients of Astragalus membranaceus and their corresponding targets;search for the disease targets of diabetes combined with coronary heart disease in the GeneCards database and OMIM database,and obtain the Astragalus membranaceus-active ingredients-target genes through Cytoscape 3.9.1 Visual network diagram;submit the disease and drug corresponding targets to Venny2.1.0 to generate intersecting targets,and build a protein interaction(PPI)network through the protein interaction(STRING)platform.Based on the Metascape 3.9.1 database,GO enrichment analysis and KEGG pathway enrichment analysis were performed to identify the biolog-ical processes and signaling pathways that may be involved.Finally,molecular docking technology was used to briefly verify the above conjecture.Results:A total of 17 key compounds of Astragalus,195 corresponding targets,and 3815 disease-related targets were obtained,which were imported into Venny2.1.0 to generate 163 intersection targets.The enrichment analysis results show that astragalus'treatment of diabetes complicated with coronary heart disease mainly involves hormone response(response to hormone),cellular response to organic cyclic compound(cellular response to organic cyclic compound),cellular response to lipid(cellular response to lipid),and inorganic matter response.(response to inorganic substance)and other biological processes;may involve pathways in cancer,lipid and atheroscierosis,and AGE-RAGE signaling pathway in diabetic complications.diabetic complications),P13K-AKt signaling pathway(P13K-AKt signaling pathway)and other signaling pathways.Molecular docking results indicate that the active drug molecule has a good combination with the core target.Conclusion:This study reveals that astragalus may be involved in inhibiting insulin resistance,regulating glucose and lipid metabolism and many other biological processes in the body,and achieves its therapeutic effect on diabetes complicated with coronary heart disease through multiple components,multiple targets and multiple pathways.
Astragalus membranaceusDiabetes complicated with coronary heart diseaseNetwork pharmacology
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