基于网络药理学探讨EGCG调控细胞焦亡对非酒精性脂肪肝疾病的作用机制  

The Mechanism of Epigallocatechin Gallate Regulating Cell Pyroptosis in Nonalcoholic Fatty Liver Disease based on Network Pharmacology

作　　者：贾旭 赵潇洋 毛丹婷 罗梓人 郭建伟 何梅[1] 赵曜[1] 兰海涛[2] 刘红[2] 郑倩[2] JIA Xu;ZHAO Xiaoyang;MAO Danting;LUO Ziren;GUO Jianwei;HE Mei;ZHAO Yao;LAN Haitao;LIU Hong;ZHENG Qian(Affiliated Hospital of North Sichuan Medical College,Nanchong 637000,China;Medical Functional Experiment Center,Basic Medical College of North Sichuan Medical College Nanchong 637000,China)

机构地区：[1]川北医学院附属医院,四川南充637000 [2]川北医学院基础与法医学院,四川南充637000

出　　处：《茶叶通讯》2023年第2期230-241,共12页Journal of Tea Communication

基　　金：川北医学院科研发展基金项目(CBY21-QA12);南充市战略合作科技专项(20SXQT0003、22SQT0132)。

摘　　要：[目的]通过网络药理学和分子对接策略探索表没食子儿茶素没食子酸酯(epigollatecatechin gallate,EGCG)改善非酒精性脂肪肝疾病(nonalcoholic fatty liver disease,NAFLD)的细胞焦亡机制。[方法]首先利用TCMSP、UniProt数据库及GeneCards筛选EGCG的潜在目标,整合GeneCards和DisGeNET数据库获取NAFLD的作用靶点,从OMIM及GeneCards数据库上收集细胞焦亡的相关目标基因。将三组基因取交集获得EGCG靶向细胞焦亡调节NAFLD的候选靶标。然后采用String数据库进行蛋白质-蛋白质相互作用(PPI)网络分析,基于DAVID平台进行共同靶点的GO功能富集和KEGG通路富集分析,Cytoscape构建靶点-信号通路网络并筛选出核心靶点。最后应用AutoDockVina进行分子对接验证。[结果]筛选出了EGCG在治疗NAFLD中作用在细胞焦亡通路上的55个共同靶点,共同靶点的GO功能和KEGG通路富集分析提示,EGCG对NAFLD中细胞焦亡的调控机制可能集中在脂质代谢(脂质和动脉粥样硬化和AGE-RAGE信号通路)、炎症反应(例如IL-17、TNF通路)、癌症相关途径(例如p53途径)和凋亡等相关途径。同时综合PPI、GO、KEGG以及分子对接情况分析NF-κB1、CASP3、AKT1等可能是主要靶点。[结论]EGCG通过多靶点、多通路调控NAFLD的细胞焦亡。[Objictive]To explore the mechanism of cell pyroptosis in nonalcoholic fatty liver disease(NAFLD)improved by epigallocatechin gallate(EGCG)through network pharmacology and molecular docking strategy.[Methods]Firstly,the potential targets of EGCG were screened by TCMSP,UniProt database and GeneCards,and the targets of NAFLD were obtained by integrating GeneCards and DisGeNET databases,and the related target genes of pyroptosis were collected from OMIM and GeneCards databases.The three sets of genes were intersected to obtain candidate targets of EGCG targeting pyroptosis to regulate NAFLD.Then,String database was used for protein-protein interaction(PPI)network analysis,and the GO functional enrichment and KEGG pathway enrichment analysis of common targets were performed based on the DAVID platform.Cytoscape constructed a target-signaling pathway network and screened out core targets.Finally,AutoDock Vina was used for molecular docking verification.[Results]Screened out 55 common targets of EGCG on the pyroptotic pathway in the treatment of NAFLD.GO and KEGG pathway enrichment analysis of common targets suggested that The regulatory mechanism of EGCG on pyroptosis in NAFLD may focus on lipid metabolism(lipid and atherosclerosis and AGE-RAGE signaling pathways),inflammatory responses(eg,IL-17,TNF pathways),cancer-related pathways(eg,p53 pathway),and apoptosis-related pathways.At the same time,NF-κB1,CASP3,AKT1 may be the main targets by comprehensive analysis of PPI,GO,KEGG and molecular docking.[Conclusion]EGCG regulates NAFLD pyroptosis through multiple targets and multiple pathways.

关 键 词：表没食子儿茶素没食子酸酯 细胞焦亡 非酒精性脂肪肝 炎症 网络药理学 分子对接 

分 类 号：S571.1[农业科学—茶叶生产加工]