基于网络药理学与分子对接探讨肝乐颗粒治疗非酒精性脂肪性肝病的作用机制  

Mechanism of Diisopropylamino Dichloroacetate Particles in Treatment of Nonalcoholic Fatty Liver Disease Based on Network Pharmacology and Molecular Docking

作　　者：俞梦圆 施卫兵[2] 许文彬 马翠翠 郭锦晨 YU Meng-yuan;SHI Wei-bing;XU Wen-bin;MA Cui-cui;GUO Jin-chen(Anhui University of Traditional Chinese Medicine,Hefei,Anhui 230012;The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine,Hefei,Anhui 230031;Xin'an Key Laboratory of Medical Science,Ministry of Education,Hefei,Anhui 230038)

机构地区：[1]安徽中医药大学,安徽合肥230012 [2]安徽中医药大学第一附属医院,安徽合肥230031 [3]新安医学教育部重点实验室,安徽合肥230038

出　　处：《按摩与康复医学》2023年第5期90-96,共7页Chinese Manipulation and Rehabilitation Medicine

基　　金：第四批全国中医(临床、基础)优秀人才研修项目(国中医药人教发[2017]24号);安徽省施卫兵名中医工作室建设项目(安徽省卫健委[中发展2020]10号)。

摘　　要：目的:基于网络药理学和分子对接的方法探讨肝乐颗粒治疗非酒精性脂肪性肝病的潜在分子作用机制。方法:通过TCMSP、Swiss TargetPrediction数据库得到肝乐颗粒中各个药物的有效活性成分及对应的蛋白质靶点,GeneCards数据库获取非酒精性脂肪性肝病的疾病靶点,利用Venny软件取药物和疾病的交集靶点,运用Cytoscape3.7.1软件创建“药物-化合物-靶点”网络图,并联合String平台对药物-疾病交集靶点进行蛋白质网络互作分析,将筛选过的核心基因导入David数据库进行GO功能富集及KEGG通路分析,应用AutoDock和Pymol软件对活性成分与关键靶点进行分子对接验证。结果:肝乐颗粒中的药物成分作用于非酒精性脂肪性肝病的靶点93个,拓扑分析出83个核心靶点信息,GO分析共包含288条生物过程、55条分子功能、33条细胞组成等376条富集结果,KEGG通路分析发现86个条目,其中主要涉及PI3K-Akt信号通路、TNF信号通路等多条信号通路。分子对接结果显示,肝乐颗粒治疗非酒精性脂肪性肝病的主要活性成分槲皮素、β-谷甾醇、山柰酚、柚皮素、异鼠李素、芒柄花素等与AKT1、JUN、CASP3、VEGFA、MMP9等蛋白结合较好。结论:本研究初步揭示了肝乐颗粒通过“多成分-多靶点-多途径”协同作用治疗非酒精性脂肪性肝病,为进一步研究肝乐颗粒治疗非酒精性脂肪性肝病的潜在作用机制提供了思路。objective:To explore the potential molecular mechanism of Ganle granule in the treatment of nonalcoholic fatty liver disease(NAFLD)based on the methods of network pharmacology and molecular docking.Methods:The effective active ingredients and corresponding protein targets of each drug in Ganle particles were obtained by TCMSP and Swiss Target Prediction database.The disease targets of non-alcoholic fatty liver disease were obtained by Gene Cards database.The intersection targets of drugs and diseases were obtained by Venny software.Cytoscape3.7.1 software was used to create a"drug-compact-target"network diagram,and the protein network interaction analysis of drug-disease intersection target was carried out jointly with String platform.The screened core genes were introduced into David database for GO enrichment and KEGG pathway analysis.AutoDock and Pymol software were used to verify the molecular docking between active ingredients and key targets.Results:There were 93 targets of drug components in Ganle granules on non-alcoholic fatty liver disease,83 core target information was obtained by topological analysis,376 enrichment results including 288 biological processes,55 molecular functions and 33 cell composition were obtained by GO analysis,and 86 items were found by KEGG pathway analysis.It mainly involves pi3K-Akt signaling pathway,TNF signaling pathway and other signaling pathways.The molecular docking results showed that the main active ingredients of Ganle granule in the treatment of nonalcoholic fatty liver disease,including quercetin,β-sitosterol,kaempferol,naringin,isorhamnetin and formononetin,had better binding with AKT1,JUN,CASP3,VEGFA and MMP9 proteins.Conclusion:This study preliminarily revealed the synergistic effect of Ganle granule on the treatment of non-alcoholic fatty liver disease(NAFLD)through"multi-component,multi-target and multi-pathway",providing ideas for the further study of the potential mechanism of action of Ganle granule on NAFLD.

关 键 词：肝乐颗粒 非酒精性脂肪性肝病 网络药理学 分子对接 机制研究 

分 类 号：R966[医药卫生—药理学]