基于网络药理学及分子对接探究茵陈蒿汤治疗自身免疫性肝炎的作用机制

Mechanism of Yinchenhao decoction in treating autoimmune hepatitis based on network pharmacology and molecular docking

目的通过网络药理学的方法,探讨使用茵陈蒿汤治疗自身免疫性肝炎可能发挥作用的关键成分以及分子机制,并通过分子对接验证结果的可靠性。方法使用TCMSP数据库筛选茵陈蒿汤有效化学成分和作用靶点,使用OMIN、DRUGBANK、Genecards和DisgenNET数据库获得自身免疫性肝炎靶点。将获得的药物与疾病靶点标准化后,使用VENNY 2.1线上工具获取交集靶点,通过Cytoscape 3.7.1软件,构建茵陈蒿汤治疗自身免疫性肝炎有效成分—靶点网络。将靶点的交集导入String,构建蛋白质相互作用网络。借助Metascape数据库对靶点进行京都基因和基因组数据库、基因本体细胞成分、基因本体分子功能和基因本体生物过程富集分析。使用Autodock Vina软件对关键化学成分和核心靶点进行分子对接。结果筛选得到茵陈蒿汤有效成分29个,其治疗自身免疫性肝炎的核心靶点分别是:白细胞介素-6、P53蛋白、肿瘤坏死因子、蛋白激酶Bα亚型和白细胞介素-1β。结论茵陈蒿汤可能通过槲皮素、山柰酚等成分作用于白细胞介素-6、P53蛋白、肿瘤坏死因子、蛋白激酶Bα亚型和白细胞介素-1β靶点,进而影响肿瘤相关信号通路、核因子κB信号通路、活性氧信号通路和趋化因子信号通路等多种相关信号通路治疗自身免疫性肝炎,该研究为深入研究茵陈蒿汤治疗自身免疫性肝炎的机制提供理论依据。

Objects To investigate the possible key components and molecular mechanisms of Yinchenhao decoction in the treatment of autoimmune hepatitis through a network pharmacology approach,and to verify the reliability of the results through molecular docking.Methods The TCMSP database was used to screen the effective chemical components and targets of action of Yinchenhao decoction,and the OMIN,DRUGBANK,Genecards,and DisgenNET databases were used to obtain autoimmune hepatitis targets.After standardizing the acquired drug and disease targets,intersecting targets were obtained using the VENNY 2.1 online tool.Afterward,the Cytoscape 3.7.1 software was used to construct an ingredient-Target network Cytodiagram for the treatment of autoimmune hepatitis with Yinchenhao decoction.The intersections of the targets were imported into the String to construct the protein-protein interaction network.We performed an enrichment analysis of targets based on Kyoto Encyclopedia of Genes and Genomes,gene ontology-cellular component,gene ontology-molecular function and gene ontology-biological process by using the Metascape database,and the molecular docking of key chemical components and core targets were performed by Autodock Vina software.Results A total of 29 effective components of Yinchenhao decoction were obtained,and the core targets of the autoimmune hepatitis treatment were interleukin-6,P53 protein,tumor necrosis factor,protein kinase Bαand interleukin-1β.Conclusion In the treatment of autoimmune hepatitis with Yinchenhao decoction,two active components quercetin and kaempferol could regulate cancer-related signaling pathways,nuclear factor-κB signaling pathway,reactive oxygen signaling pathway and chemokine signaling pathway by acting targets such as interleukin-6,P53 protein,tumor necrosis factor,protein kinase Bαand interleukin-1β.This study provides a theoretical basis for research on the mechanism of Yinchenhao decoction in treating autoimmune hepatitis.