基于网络药理学与分子对接探讨乌梢蛇治疗类风湿关节炎的作用机制

Mechanism of Zaocysdhumnades in the Treatment of Rheumatoid Arthritis Based on Network Pharmacology and Molecular Docking

目的 基于网络药理学以及分子对接技术探究乌梢蛇治疗类风湿关节炎的有效成分及作用机制。方法 通过Herb数据库及文献报道对乌梢蛇的化合物进行筛选,然后在PubChem数据库下载化合物的分子结构式,将其导入SwissTargetPrediction数据库获得有效成分所对应的靶点,利用DisGeNET、OMIM数据库筛选类风湿关节炎的相关靶点;使用在线作图工具Venny2.1.0获得乌梢蛇与类风湿关节炎共同靶点,通过Cytoscape3.10.0软件构建“药物-成分-靶点”网络,利用STRING平台与Cytoscape3.10.0软件构建蛋白-蛋白相互作用网络,通过DAVID数据库对乌梢蛇与类风湿关节炎的交集靶点进行GO功能和KEGG通路富集分析,采用CB-DOCK2进行关键成分与有效靶点的分子对接研究。结果 共得到乌梢蛇27种成分及372个潜在靶点,类风湿关节炎相关靶点1596个,乌梢蛇-类风湿关节炎共同靶点99个;乌梢蛇中的核心成分为β-谷甾醇、腺苷、二氢阿魏酸等;其中GAPDH、NR3C1和PLG是PPI网络中Betweenness最大的3个靶基因;GO分析结果显示,在生物过程(BP)中,涉及对外源性刺激的反应、蛋白水解、基因表达的正调控等;在细胞组分(CC)中,则涉及质膜、细胞质、核质等;在分子功能(MF)中,主要涉及酶结合、锌离子结合、相同的蛋白质结合等;KEGG富集分析总共得到133条通路,主要涉及的信号通路包括细胞凋亡、IL-17信号通路、癌症通路、松弛素信号通路等;分子对接结果表明,乌梢蛇的主要有效成分能分别与核心靶点结合,其结合能均小于-5.0 kcal/mol。结论 乌梢蛇可能是通过调节GAPDH、NR3C1、PLG等靶点,发挥抑制炎症反应、调节免疫功能等作用来治疗类风湿关节炎。

Objective To explore the effective components and mechanism of Zaocysdhumnades in the treatment of rheumatoid arthritis based on network pharmacology and molecular docking technology.Methods The compounds of Zaocysdhumnades were screened by Herb database and literature reports,and then the molecular structure of the compounds was downloaded from PubChem database,and then imported into SwissTargetPrediction database to obtain the targets corresponding to the active ingredients,and DisGeNET and OMIM databases were used to screen the related targets of rheumatoid arthritis.In addition,the online mapping tool Venny2.1.0 was used to obtain the common targets of Zaocysdhumnades and rheumatoid arthritis.The"drug-component-target"network was constructed by Cytoscape3.10.0 software,and the protein-protein interaction network was constructed by String platform and Cytoscape3.10.0 software.The GO function and KEGG pathway enrichment analysis of the intersection targets of Zaocysdhumnades and rheumatoid arthritis were carried out by DAVID database.CB-DOCK2 was used to study the molecular docking of key components and effective targets.Results After screening,27 components and 372 potential targets,1596 rheumatoid arthritis-related targets and 99 common targets of Zaocysdhumnades-rheumatoid arthritis related were obtained.The core components in Zaocysdhumnades wereβ-sitosterol,adenosine,dihydroferulic acid,etc.,and the three target genes with the largest betweenness in the PPI network were GAPDH,NR3C1,and PLG.The results of GO analysis showed that in the biological process(BP),it involved the response to exogenous stimulation,proteolysis,positive regulation of gene expression,etc.In the cell component(CC),it involved plasma membrane,cytoplasm,nucleoplasm,etc.In molecular function(MF),it mainly involved enzyme binding,zinc ion binding,the same protein binding,etc.A total of 133 pathways were obtained by KEGG enrichment analysis,which mainly involved signaling pathways including apoptosis,IL-17 signaling pathway,cancer pathway,relaxin signaling pathway,etc.The results of molecular docking showed that the main active ingredients of Zaocysdhumnades could bind to the core targets respectively,and the binding energy was less than-5.0 kcal/mol.Conclusion Zaocysdhumnades may be used to treat rheumatoid arthritis by regulating the targets of GAPDH,NR3C1,and PLG,inhibiting inflammatory response and regulating immune function.