基于网络药理学和分子对接技术探讨白果抗氧化作用机制

Study on Antioxidant Mechanism of Ginkgo Semen Based on Network Pharmacology and Molecular Docking Technology

目的:基于网络药理学及分子对接技术初步探讨白果抗氧化的作用机制。方法:通过TCMSP数据库收集白果活性成分及靶点;利用GeneCards、OMIM和NCBI数据库对抗氧化靶点进行收集;利用STRING数据平台对药物和疾病靶标进行蛋白质-蛋白质相互作用分析(PPI),并将结果导入Cytoscape 3.9.1软件,拓扑分析得到核心靶点;基于核心靶点通过DAVID数据库进行GO功能富集分析和KEGG通路富集分析,建立“活性成分-核心靶点-通路”网络图并进行拓扑分析,筛选得到核心成分和核心靶点。利用AutoDock Vina进行分子对接对核心成分和核心靶点的相互作用进行验证。结果:共获得白果活性成分15个,对应靶点142个,疾病靶点11255个,共有靶点139个。经过蛋白互作及拓扑分析,得到核心靶点13个,核心靶点涉及139个基因功能条目和71条通路(P<0.05)。将“活性成分-核心靶点-通路”网络图进行拓扑分析,共筛选出表没食子儿茶素没食子酸酯、槲皮素、β-胡萝卜素、山柰酚、芒柄花素、异鼠李素、β-谷甾醇和(+)-儿茶素共8个核心成分,以及CASP3、CCND1、MYC、CTNNB1、MAPK8、FOS、EGFR、VEGFA、IL6、ESR1共10个核心靶点。结论:白果抗氧化具有多成分、多靶点和多通路的作用特点,白果活性成分可能通过上调VEGFA、ESR1蛋白的表达,下调CASP3、CCND1、MYC、CTNNB1、MAPK8、EGFR、IL6蛋白的表达,激活癌症、传染病、信号传导、内分泌代谢等相关通路来实现抗氧化作用。

Objective To investigate the mechanism of Ginkgo Semen in antioxidation based on network pharmacology and molecular docking technology.Method The active ingredients and targets of Ginkgo Semen were collected through TCMSP database.GeneCards,OMIM and NCBI databases were adopted to predict antioxidation targets.Protein-Protein interaction analysis(PPI)of drugs and disease targets was constructed by STRING data platform and imported into Cytoscape 3.9.1 for further topological analysis to obtain core targets.The GO function and KEGG pathway were analyzed by DAVID database.The"active ingredient-core target-pathway"network diagram was established to screen the core ingredients and core targets using topological analysis.AutoDock Vina was employed to perform molecular docking to verify the interaction between core ingredients and core targets.Result A total of 15 active ingredients,142 corresponding targets and 11255 antioxidation related targets were obtained.139 shared targets were selected through venn diagram.After protein-protein interaction and topological analysis,13 core targets,139 gene function items and 71 pathways(P<0.05)were identified.(-)-epigallocatechin-3-gallate,quercetin,beta-carotene,kaempferol,formononetin,isorhamnetin,beta-sitosterol and(+)-catechin were core ingredients act on core targets,such as CASP3,CCND1,MYC,CTNNB1,MAPK8,FOS,EGFR,VEGFA,IL6 and ESR1 after topological analysis of the network diagram of"active ingredients-core targets-pathways".The result of molecular docking suggested that the core active ingredients had good affinity with the core targets.Conclusion Ginkgo Semen has the characteristics of multi-component,multi-target and multi-pathway in antioxidation activity.In our study,the antioxidative effects of Ginkgo Semen might be accomplished by upregulating VEGFA and ESR1 expressions and downregulating CASP3,CCND1,MYC,CTNNB1,MAPK8,EGFR and IL6 expressions through several signaling pathways including intervening cancer,infectious diseases,signal transduction,endocrine metabolism and other related pathways.Our preliminary results provide ideas and theoretical basis for the follow-up study on the antioxidant mechanism of Ginkgo Semen.