目的:基于网络药理学和分子对接技术探究海藻、昆布治疗Graves病的作用机制.方法:借助中药系统药理学数据库与分析平台(TCMSP)获得中药海藻、昆布的活性成分、靶点,运用蛋白质数据库Uniprot将靶点的基因名称规范化.分别在GeneCards、OMIM、DrugBank等数据库上检索Graves疾病靶点,使用R语言绘制海藻、昆布与Graves病交集靶点的韦恩图,并通过Cytoscape 3.8.2软件绘制"海藻、昆布-Graves病"活性成分-靶点图以及蛋白质-蛋白质相互作用网络图.利用DAVID数据库对药物与疾病交集基因进行基因本体论(GO)功能分析、京都基因与基因组百科全书(KEGG)通路富集分析.在PubChem数据库中下载小分子配体结构,在PDB数据库中下载蛋白受体结构,运用Autodock vina进行分子对接.结果:筛选出海藻、昆布与Graves病相关的活性成分11个、蛋白123个.GO功能富集分析显示,有生物过程585个、细胞组分63个、分子功能125个.KEGG通路富集分析显示,有相关通路149个.分子对接展现了具有较好相互作用的核心成分与核心蛋白的对接效果,核心成分有槲皮素和花生四烯酸,核心蛋白有Jun原癌基因(Jun Proto-Oncogene,JUN)、丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)1、肿瘤蛋白p53(Tumor Protein p53,TP53).海藻、昆布可能通过调节晚期糖基化终末产物-晚期糖基化终末产物受体(AGE-RAGE)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)等信号通路发挥治疗Graves病的作用.结论:海藻、昆布有效成分可能是槲皮素、花生四烯酸,它们分别通过JUN、MAPK1、TP53靶点蛋白,以及TNF-α、AGE-RAGE 通路治疗Graves病.
Discussion on the mechanism of iodine-rich traditional Chinese medicine Haizao and Kunbu in the treatment of Graves'disease based on network pharmacology and molecular docking
Objective:To investigate the mechanism of Haizao(Sargassum)and Kunbu(Thallus Laminariae Thallus Eckloniae)in the treatment of Graves'disease based on network pharmoacology and molecular docking.Methods:The active ingredients and their targets of the traditional Chinese medicine Haizao and Kunbu were obtained by the TCMSP,and the gene nadmes of the targets were normalized by the protein database Uniprot.The targets of Graves'disease were searched on GeneCards database,OMIM database,DrugBank database and so on.The Venn diagram of the intersection targets of Haizao,Kunbu and Graves'disease was drawn using R language.The active ingredient-target graphs and protein-protein interaction network graphs of"Haizao,Kunbu and Graves'disease"were Plotted by Cytoscape 3.8.2 software.GO functional analysis and KEGG pathway enrichment analysis of drug-disease intersecting genes were performed using the DAVID database.Small molecule ligand structures were downloaded from PubChem database,protein receptor structures were downloaded from PDB database,and molecular docking was performed using Autodock vina.Results:The screening showed that there were 11 active components and 123 proteins associated with Graves'disease in Haizao and Kunbu.GO functional enrichment analysis showed 585 biological processes,63 cellular components and 125 molecular functions.KEGG pathway enrichment analysis showed 149 associated pathways.Molecular docking showed the results of docking core components with better interaction with core proteins.The core components were quercetin,arachidonic acid,and the core proteins were JUN,MAPK1,and TP53.Haizao and Kunbu might play a role in the treatment of Graves'disease by regulating AGE-RAGE,TNF and other signaling pathways.Conclusion:The active ingredients of Haizao and Kunbu may be quercetin and arachidonic acid,which treat Graves'disease through JUN,MAPK1,TP53 target proteins,and TNF-α and AGE-RAGE pathways,respectively.
万方数据
维普
