基于网络药理学和分子对接技术探讨绿豆防治酒精性肝损伤的潜在作用机制

The Potential Mechanism of Mung Bean in the Prevention and Treatment of Alcoholic Liver Injury Based on Network Pharmacology and Molecular Docking Technology

目的:运用网络药理学联合分子对接技术探讨绿豆防治酒精性肝损伤的潜在作用机制。方法:通过TCMSP数据库和文献挖掘进行绿豆主要活性物质的收集及筛选,应用Swiss Target Prediction数据库获取靶标;利用Gene Cards数据库收集酒精性肝损伤的相关基因,并与活性成分取交集作为绿豆防治酒精性肝损伤的潜在作用靶点,将该潜在作用靶点导入Cytoscape3.9.0软件构建相互作用网络图;将潜在作用靶点导入DAVID数据库对核心治疗靶点进行GO功能注释和KEGG通路富集分析。交集靶基因上传至STRING数据库,获得PPI数据。基于拓扑学分析筛选关键药效成分与核心靶点,利用Sybyl软件对关键活性成分与核心靶点进行分子对接验证,并运用pymol进行可视化处理。结果:结果显示基于数据库及文献收集绿豆活性成分21个,545个酒精性肝损伤相关的疾病靶点,应用Cytoscape3.9.0插件获得其生物靶点网络(273个节点,563条边),其中黄酮类化合物发挥重要作用,KEGG富集分析显示参与了AGE-RAGE signaling pathway in diabetic complications等生物过程,分子对接结果得染料木黄酮可与HSP90AA1、TP53等靶点成功对接,发挥防治酒精性肝损伤的作用。结论:揭示了绿豆防治酒精性肝损伤的多成分、多靶点、多途径的作用特点,为其新药开发和作用机制研究提供了理论基础。

Objective:To investigate the potential mechanism of action of Vigna radiate L.against alcoholic liver injury using network pharmacology combined with molecular docking technique.Method:The main active substances of mung bean were collected and screened by TCMSP database and literature mining,and the targets were obtained by SwissTargetPrediction database;the genes related to alcoholic liver injury were collected by Gene Cards database,and the intersection which was made with the targets of the active ingredient was taken as the potential target of mung bean for the prevention and treatment of alcoholic liver injury.The potential targets were imported into Cytoscape3.9.0 software to construct the interaction network;the potential targets were imported into DAVID database for gene ontology(GO)function annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)for the core therapeutic targets.Pathway enrichment analysis.Cross-linked target genes were uploaded to the STRING database to obtain PPI data.According to the topological analysis,the key pharmacodynamic components and core targets were selected.The molecular docking verification of key active components and core targets was carried out by Sybyl software,and pymol was used for visualization.Result:The results showed that based on database and literature,21 active ingredients of mung bean were collected,545 disease targets related to alcoholic liver injury were collected,and its biological target network(273 nodes,563 edges)was obtained by applying Cytoscape plugin,in which flavonoids played an important role.KEGG enrichment analysis showed that the flavonoids were involved in AGE-RAGE signaling pathway in diabetic complications and other biological processes,and the molecular docking results showed that genistein flavonoids could be successfully docked with HSP90AA1 and TP53 to prevent and treat alcoholic liver injury.Conclusion:This study reveals the multi-component,multi-target and multi-pathway action characteristics of mung bean for the prevention and treatment of alcoholic liver injury,providing a theoretical basis for its new drug development and action mechanism research.