基于网络药理学探究积雪草酸抗酒精性肝炎的作用机制

Mechanism of asiatic acid in alcoholic hepatitis based on network pharmacology

目的应用网络药理学与体内实验验证的方法,探讨积雪草酸(asiatic acid,AA)对酒精性肝炎(alcoholic hepatitis,AH)的作用机制。方法通过数据检索、网络构建与富集分析的方法探索AA对AH的潜在作用机制。同时,每日灌胃SD大鼠酒精诱导酒精性肝炎模型,检测与AH相关的关键指标,包括血生化指标、炎症反应、酒精代谢、肝组织病理变化和NF-κB通路中关键蛋白的表达。结果筛选出AA与AH共同作用靶点24个,富集分析得到20条信号通路和12条GO功能条目,本实验重点研究排在第一位的hsa05200:Pathways in cancer的NF-κB信号子通路。体内实验结果显示,积雪草酸能明显降低大鼠血清中ALT和AST含量,提高ADH和ALDH的活性,明显降低肝脏TNF-α和GSH的水平;此外,积雪草酸还可以明显抑制p-IKKα/β、p-IκBα和p-NF-κB蛋白表达。结论积雪草酸对酒精导致的大鼠肝炎有一定的改善作用。

Aim To explore the mechanism of asiatic acid(AA)on alcoholic hepatitis(AH)based on the network pharmacology and experimental verification in vivo methods.Methods The potential mechanism of AA on AH was explored by data collection,network construction,and enrichment analysis.Meanwhile,the model of alcoholic hepatitis disease was induced by intragastric administration of edible alcohol every day in SD rats.The key related indicators were detected,including biochemical markers,inflammatory responses,alcohol metabolism,pathological changes in liver tissues,and the expression of proteins of the NF-κB pathway.Results A total of 24 overlapping targets of AA and AH were screened out,and 20 signaling pathways and 12 GO functional entries were obtained.This study focused on the first pathway,hsa05200:Pathways in cancer.The pathway contained NF-κB signaling pathway.In vivo results showed that AA significantly reduced the serum levels of ALT and AST,increased the levels of alcohol metabolism and decreased the liver content of TNF-αand GSH.Additionally,AA significantly inhibited p-IKKα/β,p-IκBαand p-NF-κB protein expressions.Conclusion Asiatic acid can alleviate the liver damage and inflammation induced by alcohol in rats.