基于网络药理-分子对接探讨乌药治疗酒精性肝炎的作用机制

Investigation on the mechanism of Linderae Radix in the treatment of alcoholic hepatitis based on network pharmacology-molecular docking

目的基于网络药理-分子对接,探讨乌药治疗酒精性肝炎的作用机制。方法通过中药网络药理学数据库鉴定乌药的活性成分;利用BATMAN和Swiss target prediction预测活性成分的靶蛋白;与CTD、GeneCards数据库的疾病相关基因进行整合,取交集作为潜在靶蛋白。然后,进行功能和信号通路富集分析,构建“活性分子-靶点-通路”网络,使用AutoDock对活性分子和靶蛋白进行分子对接。结果筛选活性成分33个,鉴定了1019个靶标,其中27个靶蛋白被认为是乌药治疗酒精性肝炎的关键分子。功能富集分析结果表明,这些靶蛋白主要涉及白细胞迁移、细胞黏附的正向调节、Toll样受体通路、TNF信号通路、酒精性肝病等。分子对接显示,槲皮素、亚油酸和石梓呋喃与关键靶蛋白(CXCL8、IL1B、IL-6等)存在相互作用,且主要通过氢键相互连接。结论本研究揭示了乌药的关键活性成分可通过多种蛋白及通路发挥治疗效应,为进一步研究乌药治疗酒精性肝炎的作用机制提供依据。

Objective To investigate the mechanism of Linderae Radix in the treatment of alcoholic hepatitis based on network pharmacology-molecular docking.Methods The active ingredients of Linderae Radix were identified through the network pharmacology database of Chinese materia medica;BATMAN and Swiss target prediction were used to predict the target proteins of active ingredients.Through the integration of disease-related genes in CTD and GeneCards databases,the intersection was taken as a potential target protein.Then,the enrichment analysis of function and signal pathway was carried out,and the"activity-target-pathway"network was constructed.AutoDock was used for molecular docking between active molecules and target proteins.Results A total of 33 active ingredients were screened and 1019 targets were identified,in which 27 target proteins were considered as key molecules in the treatment of alcoholic hepatitis by Linderae Radix.The results of functional enrichment analysis showed that these target proteins mainly involved in leukocyte migration,positive regulation of cell adhesion,Toll-like receptor pathway,TNF signaling pathway,alcoholic liver disease,etc.Molecular docking showed that quercetin,linoleic acid and Catalpa furan interacted with key target proteins(CXCL8,IL1B,IL-6,etc.),and they were mainly interconnected by hydrogen bonds.Conclusion This investigation reveals that the key active ingredients of Linderae Radix can exert therapeutic efficacies through a variety of proteins and pathways,and provide a basis for further research on the mechanism of Linderae Radix in the treatment of alcoholic hepatitis.