摘要
目的 应用网络药理学和分子对接技术探讨藤黄中主要成分藤黄酸(GA)在牙周炎治疗中的作用及分子机制.方法 使用SwissTargetPrediction、SEA及SuperPred数据库获取GA的相关靶点;利用GeneCards、DisGeNET及CTD数据库获取牙周炎的相关靶点;通过构建韦恩图获取药物和疾病的共同靶点;将共同靶点上传至STRING在线平台构建共同靶点"蛋白质-蛋白质相互作用(PPI)网络",并运用Cytoscape 3.10.0软件对PPI网络进行可视化处理并筛选出关键靶点;使用Metascape数据库对关键靶点进行GO富集分析和KEGG富集分析,并构建"KEGG通路-关键靶点"网络图;通过PDB数据库获取药物关键靶点度值前10的靶点蛋白pdb文件,使用AutoDock4软件进行分子对接.结果 获得"药物-疾病"共同靶点185个,包括STAT3、CASP3、TLR4、HIF1-α、MTOR、STAT1、ITGB1、HDAC1、ITGB3、CASP8 等核心靶点;KEGG 分析共获得 141 条信号通路,包括中性粒细胞胞外诱捕网(NETs)形成、PI3K-AKT、Toll样受体等多条信号通路;分子对接结果显示GA与对应关键靶点结合能均≤-5 kJ/mol,药物结合能力较好.结论 GA可通过参与NETs形成、PI3K-AKT、Toll样受体等通路,调节免疫反应、炎症反应、组织修复,发挥对牙周炎的治疗作用.
Abstract
Objective To investigate the role and molecular mechanism of gambogic acid(GA)in the treatment of periodontitis by network pharmacology and molecular docking.Methods SwissTargetPredicton,SEA and SuperPred databases were used to obtain the related targets of GA.The related targets of periodontitis were retrieved from GeneCards,DisGeNET and CTD databases.Common targets for drugs and diseases were obtained by constructing Venn diagrams.The common targets were uploaded to the STRING online platform to construct"protein-protein interaction(PPI)network"of common targets,and the PPI network was visualized by Cytoscape 3.10.0 software to screen out key targets.Metascape database was used to conduct GO enrichment analysis and KEGG enrichment analysis for key targets,and the"KEGG pathway-key target"network diagram was constructed.The pdb files of the top 10 key targets were obtained from the PDB database.Molecular docking was performed using AutoDock4 software.Results A total of 185"drug-disease"common targets were obtained,including STAT3,CASP3,TLR4,HIF1-α,MTOR,STAT1,ITGB1,HDAC1,ITGB3,CASP8 and other core targets.A total of 141 signaling pathways were obtained by KEGG analysis,including neutrophil extracellular traps(NETs)formation,PI3K-AKT signaling pathway,Toll-like receptor signaling pathway and other signaling pathways.Molecular docking results showed that the binding energies of GA and corresponding key targets were ≤-5 kJ/mol,and drug-target binding ability was good.Conclusion GA can regulate immune response,inflammatory response,and tissue repair by participating in NETs formation,PI3K-AKT signaling pathway,Toll-like receptor signaling pathway and other signaling pathways,and play a therapeutic role in periodontitis.
基金项目
广东省基础与应用基础研究项目(2020A1515110800)
维普
万方数据