基于网络药理学及分子对接探讨乌丹降脂胶囊治疗非酒精性脂肪肝的作用机制  

Mechanism of Wudan lipid-lowering capsule in the treatment of non-alcoholic fatty liver disease:Based on network pharmacology and molecular docking

作　　者：李圣豪 戴慕巍 王芳[3] 冯彩霞[1] 贾彦生[4] 王超[1] 郝立园 李耀琪 闫会敏[6] LI Shenghao;DAI Muwei;WANG Fang;FENG Caixia;JIA Yansheng;WANG Chao;HAO Liyuan;LI Yaoqi;YAN Huimin(Department of Pharmacy,The Fifth Hospital of Shijiazhuang,Shiji-azhuang,Hebei 050021;Department of Orthopedics,The Fourth Hospital of Hebei Medical University,Shijiazhuang,Hebei 050011;Epidemiology Teaching and Research Office,Hebei Medical University,Shijiazhuang,Hebei 050017;Department of Digestive Endoscopy,The Fifth Hospital of Shijiazhuang,Shijiazhuang,Hebei 050021;Hebei University of Chinese Medicine,Shijiazhuang,Hebei 050200;Institute of Clinical Medicine,The Fifth Hospital of Shijiazhuang,Shijiazhuang,Hebei 050021)

机构地区：[1]河北省石家庄市第五医院药剂科,河北石家庄050021 [2]河北医科大学第四医院骨科,河北石家庄050011 [3]河北医科大学流行病学教研室,河北石家庄050017 [4]河北省石家庄市第五医院消化内镜室,河北石家庄050021 [5]河北中医学院,河北石家庄050200 [6]河北省石家庄市第五医院临床医学研究所,河北石家庄050021

出　　处：《河北中医》2022年第12期2077-2086,共10页Hebei Journal of Traditional Chinese Medicine

基　　金：河北省科学技术厅重点研发计划项目(编号:223777156D);河北省中医药管理局2021年度中医药类科研指令性计划课题(编号:2021226)。

摘　　要：目的基于网络药理学探讨乌丹降脂胶囊治疗非酒精性脂肪肝(NAFLD)的活性成分和作用靶点。方法通过中医药百科全书(ETCM)数据库获取乌丹降脂胶囊的活性成分和靶点,并构建成分-靶点网络。通过GeneCards、OMIM和TTD等疾病数据库筛选出NAFLD的作用靶点。乌丹降脂胶囊和NAFLD相关靶点进行Venn分析,寻找交集靶点。通过Cytoscape 3.8.2软件构建“药物-成分-靶点”网络图。利用STRING 11.5数据库及Cytoscape 3.8.2软件进行蛋白质-蛋白质相互作用(PPI)网络构建及分析;然后采用DAVID数据库进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析,最后运用AutoDock Tools 1.5.6软件将核心活性成分与核心靶点进行分子对接。结果获得乌丹降脂胶囊的有效成分393种,作用靶点812个,NAFLD相关靶点1142个,“药物-疾病”交集靶点共107个;乌丹降脂胶囊治疗NAFLD的核心活性成分为阿里红酸,其次为棕榈酸和辛酸等,核心靶点为过氧化物酶体增殖物激活受体α(PPARA)、胰岛素(INS)、过氧化物酶体增殖物激活受体γ(PPARG)、白细胞介素6(IL-6)、Toll样受体4(TLR4)、肿瘤坏死因子(TNF)、细胞色素P450家族2亚科E成员1(CYP2E1)、肌动蛋白β(ACTB)、白蛋白(ALB)和热休克蛋白90α家族A级成员1(HSP90AA1)。交集靶点共涉及GO分析43个条目,KEGG通路共7条通路。分子对接显示阿里红酸与核心靶点PPARA、CYP2E1、TNF、ACTB、ALB结合性较好。结论乌丹降脂胶囊通过多靶点、多成分、多通路治疗NAFLD,为进一步的实验研究提供了理论基础和实验依据。Objective To explore the active ingredients and targets of Wudan lipid-lowering capsule for non-alcoholic fatty liver disease(NAFLD)based on the network pharmacology.Methods The active ingredients and targets of Wudan lipid-lowering capsule were obtained from the Encyclopedia of Traditional Chinese Medicine(ETCM)database to construct the ingredient-target network.The Gene Cards database,Online Mendelian Inheritance in Man(OMIM)database,Therapeutic Target Database(TTD)were used to screen out NAFLD targets.Wudan lipid-lowering capsule and targets related to NAFLD were analyzed by Venn analysis to find intersection targets.The"drug-ingredient-target"network diagram was constructed by Cytoscape 3.8.2 software.Construction and Analysis of Protein-Protein Interaction Network were performe by STRING 11.5 database and Cytoscape 3.8.2 software.Then,the enrichment analysis of Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were conducted by the Database for Annotation,Visualization,and Integrated Discovery(DAVID).Finally,the Auto Dock Tools 1.5.6 software was used to carry out molecular docking of the main active ingredient and the core target.Results In Wudan lipid-lowering capsule,there are 393 active ingredients,812 action targets,1142 non-alcoholic fatty liver related targets,and 107"drug-disease"intersection targets.The key ingredients of Wudan lipid-lowering capsule for non-alcoholic fatty liver was officinalic acid,followed by peroxisome proliferator-activated receptorα(PPARα),insulin(INS),peroxisome proliferator-activated receptorγ(PPARγ),interleukin 6(IL-6),toll-like receptor Body 4(TLR4),tumor necrosis factor(TNF),cytochrome P450 family 2 subfamily E member 1(CYP2E1),actin beta(ACTB),albumin(ALB)and heat shock protein 90αfamily class A member 1(HSP90AA1).The intersection targets involved 43 GO items and 7 KEGG pathways.Molecular docking showed that officinalic acid had good binding with the sekey targets(PPARA、CYPZE1、TNF、ACTB、ALB).Conclusion Wudan lipid-lowering capsule tre

关 键 词：脂肪肝 中药 药理学 乌丹降脂胶囊 

分 类 号：R285[医药卫生—中药学] R575[医药卫生—中医学] R283.65