摘要
目的:基于网络药理学和分子对接技术探讨蔓荆子防治急性心肌梗死(AMI)的作用机制。方法:应用中药系统药理学数据库与分析平台(TCMSP)对蔓荆子的有效成分及作用靶点进行筛选,通过SwissTargetPrediction平台进行补充;利用UniPort数据库注释靶点基因;通过GeneCards、DisGeNET、TTD、OMIM数据库获取AMI的疾病靶点;将药物靶点与疾病靶点取交集,采用Cytoscape 3.9.1软件构建“药物-药物化合物-靶点”可视化网络图;应用Rstudio 4.1.3通过Bioconductor数据库对交集靶点进行基因本体(GO)及京都基因与基因组百科全书(KEGG)通路富集分析;通过STRING数据库对交集靶点进行蛋白相互作用(PPI)分析,利用Cytoscape 3.9.1软件CytoHubba插件对PPI网络进行分析,获得关键靶点。通过AutoDock Tools 1.5.7软件和Pymol 2.4.0对部分关键靶点蛋白受体和化合物配体进行分子对接验证和可视化分析。结果:筛选得到蔓荆子中的活性成分共计27个,药物与疾病交集靶点185个;通过蔓荆子-药物化合物-靶点网络模型发现其防治AMI的主要活性成分为槲皮素、木犀草素、山柰酚、豆甾醇、牡荆素C;GO分析显示主要与调节脂多糖应答的生物过程相关,KEGG通路富集分析显示主要作用机制可能与脂质和动脉粥样硬化、糖尿病并发症受体信号通路、血流剪切应力与动脉粥样硬化、白细胞介素-17(IL-17)信号通路、肿瘤坏死因子(TNF)信号转导通路有关。结论:蔓荆子对AMI的干预作用具有多成分、多靶点、多通路、多环节的调控特点,可能通过调节脂代谢、抗炎、免疫调节、促进血管生成以及调节细胞自噬等过程发挥治疗作用。
Objective:To explore the mechanism of Viticis Fructus in the prevention and treatment of acute myocardial infarction(AMI)through network pharmacology and molecular docking.Methods:Traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)database was used to screen the active components and target of Viticis Fructus,and SwissTarget Prediction platform was used to complement them.UniPort database was used to annotate target genes.Disease targets of AMI were obtained from GeneCards,DisGeNET,TTD,and OMIM databases.The intersection of drug targets and disease targets was established using Cytoscape 3.9.1 software to construct the"drug-drug compound-target"visual network diagram.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genome(KEGG)pathway enrichment analysis of intersection targets was performed using Rstudio 4.1.3 through Bioconductor database.The intersection targets were analyzed for protein-protein interaction(PPI)using STRING database,and the PPI network was analyzed using CytoHubba plugin of Cytoscape 3.9.1 software to obtain key targets.AutoDock Tools 1.5.7 software and Pymol 2.4.0 software were used for molecular docking verification and visual analysis of some key target protein receptors and compound ligands.Results:A total of 27 effective components were selected from Viticis Fructus,there were 185 intersection targets of drugs and diseases.Through the Viticis Fructus-drug compound-target network model,it was found that the main active ingredients for the prevention and treatment of AMI were quercetin,luteol,kaempferol,stigmasterol,and vitexin C.The results of GO analysis were mainly related to the biological processes that regulate the response of lipopolysaccharide.The enrichment analysis of KEGG pathway showed that the main mechanism of action might be related to lipid and atherosclerosis,diabetes complications receptor signaling pathway,blood flow shear stress and atherosclerosis,interleukin-17 signaling pathway,and tumour necrosis factor signal transduction pathway.Conclusion:The intervention effect of Viticis Fructus on AMI is characterized by multi-component,multi-target,multi-pathway,and multi-link regulation.It may play a therapeutic role through lipid metabolism,anti-inflammatory,immune regulation,promoting angiogenesis,and regulating autophagy.
作者
陈礼琴
徐彤彤
吕祥威
武琦
覃秋语
赵位昆
CHEN Liqin;XU Tongtong;LYU Xiangwei;WU Qi;QIN Qiuyu;ZHAO Weikun(Affiliated Hospital of Guilin Medical University,Guilin 541001,Guangxi,China)
出处
《中西医结合心脑血管病杂志》
2023年第21期3863-3874,共12页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
国家自然科学基金项目(No.82260864)
广西自然科学基金项目(No.2020GXNSFAA297009)。
关键词
急性心肌梗死
蔓荆子
网络药理学
分子对接
acute myocardial infarction
Viticis Fructus
network pharmacology
molecular docking
