基于网络药理学和分子对接探讨茵太养肝方治疗药物性肝损伤的作用机制

Exploring the Therapeutic Mechanism of Yintai Yanggan Formula in Treating Drug-Induced Liver Injury Based on Network Pharmacology and Molecular Docking

摘要: 目的：基于网络药理学分析茵太养肝方治疗药物性肝损伤(DILI)的潜在作用靶点和信号通路，并通过分子对接技术进一步阐明其治疗DILI的具体机制。方法：通过中药系统药理学数据库与分析平台(TCMSP)和uniport数据库以及GeneCards和OMIM数据库，获取茵太养肝方活性成分和作用靶点以及DILI靶点。利用Veeny 2.1在线工具、Cytoscape软件和STRING数据库分别进行韦恩图绘制、化合物–靶点网络和蛋白–蛋白互作(PPI)网络。利用R软件和Metascape进行GO和KEGG信号通路富集分析。采用AutoDock和PyMol3.1软件进行分子对接验证。结果：获取到茵太养肝方潜在有效活性成分75个和215个作用靶点，197个复方–疾病交集靶点，核心靶点21个；KEGG主要富集在脂质与动脉粥样硬化和PI3K/Akt等相关的信号通路上。分子对接结果显示，关键靶点AKT1、TNF和TP53等与主要活性成分槲皮素、汉黄芩素、β-谷甾醇均对接稳定。其中，AKT1与β-谷甾醇、槲皮素结合性最好。结论：茵太养肝方中的槲皮素、β-谷甾醇等活性成分，可能作用于AKT1和TNF等靶点，通过调控脂质与动脉粥样硬化、PI3K/Akt等信号通路，发挥抗炎、抗氧化和抗细胞凋亡的作用以及参与肝细胞活化、增殖和分化过程从而起到治疗药物性肝损伤的作用。

Abstract: Objective: Based on network pharmacology analysis, the potential targets and signaling pathways of Yintai Yanggan Formula in treating drug-induced liver injury (DILI) were identified, and the specific mechanism of its treatment for DILI was further elucidated through molecular docking technology. Method: The active ingredients and targets of Yintai Yanggan Formula, as well as disease targets related to DILI, were obtained through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), uniport database, GeneCards and OMIM database. Use Veeny 2.1 online tool, Cytoscape software, and STRING database to draw Venn diagrams, drug target interaction network diagrams, and protein-protein interaction (PPI) networks, respectively. Perform GO and KEGG signaling pathway enrichment analysis using R software and Metascape platform. Molecular docking validation was performed using AutoDock and PyMol3.1 software. Result: 75 potential active ingredients and 215 action targets, 197 compound disease intersection targets, and 21 core targets were obtained from Yintai Yanggan Formula; KEGG is mainly enriched in the signaling pathways related to lipid and atherosclerosis and PI3K/Akt. The molecular docking results showed that the key targets AKT1, TNF, and TP53 were stably docked with the main active ingredients quercetin, baicalein, and beta-sitosterol. Among them, AKT1 has the best binding affinity with beta-sitosterol and quercetin. Conclusion: The active ingredients such as quercetin and beta-sitosterol in Yintai Yanggan Formula may act on targets such as AKT1 and TNF, and play the role of anti-inflammation, anti-oxidation and anti-apoptosis, and participate in the process of liver cell activation, proliferation and differentiation to treat drug-induced liver injury by regulating lipid and atherosclerosis, PI3K/Akt and other signal pathways.