基于网络药理学探讨4-乙酰氧基苯并噁唑-2-酮对急性肝损伤的作用机制

Study on the mechanism of 4-acetoxybenzoxazol-2-one on acute liver injury based on net⁃work pharmacology

目的:通过网络药理学方法探讨4-乙酰氧基苯并噁唑-2-酮(AcO-BOA)对急性肝损伤(ALI)的作用机制,并运用分子对接技术和动物实验进行验证。方法:采用ChemDraw绘制AcO-BOA的结构式,Swiss Target Prediction、Phammapper、Gene-Cards、OMIM数据库筛选药物和疾病ALI的靶点;通过Venny 2.1.0在线平台,获取药物与ALI的共同靶点,String在线数据库构建蛋白质相互作用(PPI)网络图,利用Cytohubba筛选核心靶点。David数据库进行GO和KEGG富集分析且运用Omicshare在线工具可视化。运用AutoDockTools-1.5.6进行分子对接验证,最后将预测结果进行动物实验初步验证。结果:共筛选到药物靶点268个,疾病靶点2119个,药物与疾病的交集靶点共52个。GO和KEGG富集共涉及111条生物学过程和38条信号通路,分子对接结果显示AcO-BOA能与核心靶点自发结合。动物实验结果表明,AcO-BOA能够改善小鼠肝功能,Western blotting结果表明,AcO-BOA能降低p-AKT/AKT的表达。结论:AcO-BOA能够通过多靶点,多通路发挥防治ALI作用,其作用机制可能与调控PI3K-AKT通路有关。

Objective:To explore the mechanism of 4-acetoxybenzoxazol-2-one(AcO-BOA)on acute liver injury(ALI)through network pharmacology,and further clarify its mechanism by molecular docking methods and animal experiments.Methods:The structural formula of AcO-BOA was drew by ChemDraw,the targets of drugs and ALI were screened from the Swiss Target Prediction,Phammapper,GeneCards and OMIM database;meanwhile,the common targets of drugs and diseases were obtained from the Venny 2.1.0 online platform,a protein interaction network(PPI)was constructedby the String online database,and the core targets were screened from Cytohubba.And then the GO and KEGG enrichment were analyzed by David database and the visualization was retrieved by Omicshare online tool.Finally,the AutoDockTools-1.5.6 was used for molecular docking verification,and the prediction results were verified by animal experiments.Results:In this study,a total of 268 drug targets,2,119 disease targets,and 52 drug-disease intersection targets were screened.The enrichment of GO and KEGG involved 111 biological processes and 38 signal pathways.The results of molecular docking indicated that AcO-BOA could spontaneously bind to the core targets.The results of animal experiments showed that AcO-BOA improved the liver function of mice,and the results of Western blot showed that AcO-BOA reduced the expression of p-AKT/AKT.Conclusion:AcO-BOA can prevent and treat acute liver injury through multiple targets and multiple pathways,and its mechanism may be related to the regulation of PI3K-AKT pathway.