基于网络药理学及分子对接探讨青龙衣抗胃炎作用的潜在靶点和分子机制

Mechanism of Qinglongyi on Anti-Gastritis Effect Based on Network Pharmacology and Molecular Docking

目的 考察青龙衣对大鼠胃炎模型的保护作用,并采用网络药理学和分子对接方法,探讨青龙衣发挥抗炎、免疫作用的潜在靶点和分子机制。方法 建立大鼠胃炎模型,考察青龙衣醇提物对大鼠胃组织形态变化、生化指标的影响,并运用TCMSP、Swiss Target Prediction、GeneCards、DisGeNET及OMIM等数据库,对青龙衣的活性成分、作用靶点及疾病靶点进行检索归纳,Cytoscpe软件进行成分-靶点网络图构建,主要核心靶点通过DAVID数据库,进行基因本体(GO)功能分析与基因组百科全书(KEGG)通路富集分析,最后采用AutoDock软件进行分子对接验证。结果 实验表明,青龙衣醇提物对大鼠胃炎具有一定的改善作用,可以提高抗氧化活性,降低炎性因子水平;进一步筛选出青龙衣活性成分46个,潜在作用靶点156个。GO功能分析表明,青龙衣发挥抗胃炎作用的机制可能是通过调节信号传导、改变核受体活性、与蛋白结合等发挥作用;KEGG分析表明,青龙衣通过调节PI3K-AKT通路、TNF信号通路、FoxO信号通路等发挥作用;分子对接结果表明,配体和受体的结合能均<-20.9 kJ·mol^(-1),表明配体和受体有良好的结合性。结论 青龙衣具有抗胃炎作用,其发挥作用的主要活性成分为黄酮类、萘醌类等,涉及的主要靶点有AKT1、SRC、MAPK14、MAPK1等,遵循了中药多成分、多靶点、多途径的作用特点,为后续研究青龙衣抗胃炎作用提供参考。

OBJECTIVE To investigate the protective effect of Qinglongyi on rat gastritis model,and explore the potential targets and molecular mechanisms of Qinglongyi′s anti-inflammatory and immune effects by using network pharmacology and molecular docking methods.METHODS A rat model of gastritis was established and the effects of the ethanol extract of Qinglongyi was investigated on the morphological changes and biochemical parameters of gastric tissue in rats,and the active ingredients,action targets and disease targets of Qinglongyi were searched and summarized by using TCMSP database,Swiss Target Prediction database,GeneCards database,DisGeNET database and OMIM database,and the component target network diagram was constructed by Cytoscpe software.The main core targets were identified by DAVID database,GO function analysis and KEGG pathway enrichment analysis were carried out,and finally the molecular docking validation was carried out using AutoDock software.RESULTS It was found that the ethanol extract of Qinglongyi could improve the gastritis of rats,increase the antioxidant activity and reduce the level of inflammatory factors.Forty-six active ingredients of Qinglongyi were further screened and 156 potential targets were identified.GO function analysis and KEGG pathway enrichment analysis show that the mechanism of Qinglongyi′s anti-gastritis effects may be through regulating signal transduction,changing nuclear receptor activity and binding with protein,and anti-gastritis effects by regulating PI3K-AKT pathway,TNF signal pathway and FoxO signal pathway.Molecular docking results show that the binding energy of ligand and receptor is less than-20.9 kJ·mol^(-1),indicating that ligand and receptor have good binding.CONCLUSION Qinglongyi has a good anti-gastritis effect and its main active ingredients are flavonoids and naphthoquinones.The main targets involved are AKT1,SRC,MAPK14 and MAPK1.Following the characteristics of multi-component,multi-target and multi-channel of traditional Chinese medicine,it provides references for the follow-up study on the anti-gastritis effect of Qinglongyi.