基于网络药理学和分子对接探讨“黄连-茵陈”治疗慢性萎缩性胃炎机制  

Pharmacological mechanism of the traditional Chinese medicine herbal pair of Rhizomacoptidis and Artemisia capillaris in the treatment of chronic atrophic gastritis based on the network pharmacology and molecular docking

作　　者：李泽 杨柳[1,2,3] 高云霄 胡婧楠 张彤 王小天 李博林[1,2,3] LI Ze;Yang Liu;Gao Yunxiao;Hu Jingnan;Zhang Tong;Wang Xiao tian;Li Bolin(The Third Department of Spleen and Stomach,the First Affiliated Hospital of Hebei College of Traditional Chinese Medicine,Shijiazhuang,Hebei 050011;Hebei Key Laboratory of Turbidity Toxin Syndrome,Shijiazhuang,Hebei 050011;Hebei Industrial Technology Institute for Traditional Chinese Medicine Preparation,Hebei Shijiazhuang 050011;Respiratory Department of the Fourth Hospital of Hebei Medical University,Shijiazhuang,Hebei 050011;Hebei University of Traditional Chinese Medicine,Shijiazhuang,Hebei 050090)

机构地区：[1]河北中医学院第一附属医院脾胃三科,河北石家庄050011 [2]河北省浊毒证重点实验室,河北石家庄050011 [3]河北省脾肾病证中医治疗技术创新中心,河北石家庄050011 [4]河北医科大学第四医院呼吸内科,河北石家庄050011 [5]河北中医学院,河北石家庄050090

出　　处：《河北中医》2023年第4期658-667,共10页Hebei Journal of Traditional Chinese Medicine

基　　金：东部地区名老中医学术观点、特色诊疗方法和重大疾病防治经验研究项目(编号:2018YFC1704102);河北省重点研发计划项目(编号:21377724D,21377740D);河北省中医药管理局科研计划项目(编号:2022026)。

摘　　要：目的基于网络药理学和分子对接研究探讨“黄连-茵陈”药对治慢性萎缩性胃炎(CAG)的作用机制。方法在中药系统药理学数据库与分析平台(TCMSP)中检索获得“黄连-茵陈”药对的活性成分、作用靶点及分子结构,建立数据集,再通过GeneCard、CTD、TTD数据库筛选CAG疾病靶点,与“黄连-茵陈”药对活性化合物作用靶点取交集,利用Cytoscape软件构建“药物-成分-靶点-疾病”网络,利用STRING数据库及Cytoscape软件构建蛋白质-蛋白质相互作用(PPI)网络,通过聚类分析获取核心成分与核心靶点,利用DAVID数据库对交集靶点进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析,最后利用AutoDok Tool、Pymol软件将核心靶点与核心成分进行分子对接验证。结果经筛选获得“黄连-茵陈”药对活性化合物26种,筛选后活性化合物对应靶点86个,CAG靶点639个,“黄连-茵陈”活性化合物成分与CAG交集靶点38个,核心成分为槲皮素、异鼠李素、β-谷甾醇等,高于平均Degree值的靶点蛋白有白细胞介素6(IL-6)、肿瘤坏死因子(TNF)、Ju-Nana原癌基因(JUN)等。通过GO功能富集分析得到生物过程(BP)98个,包括核糖核酸(RNA)聚合酶Ⅱ启动子转录的正调控、一氧化氮生物合成过程的正调控、基因表达的正调控等;细胞组分(CC)21个,包括细胞外空间、胞外区、细胞表面等;分子功能(MF)18个,包括酶结合、转录因子结合、细胞因子活性等。KEGG通路富集分析得到通路54条,涉及癌症信号通路、TNF信号通路、丝裂原活化蛋白激酶(MAPK)信号通路等。分子对接结果显示化合物与靶蛋白之间结合良好,可以形成稳定结构。结论“黄连-茵陈”药对中多种有效成分可通过多靶点、多信号通路抑制CAG向胃癌进展,甚至逆转萎缩。Objective To explore the pharmacological mechanism of the traditional Chinese medicine(TCM)herbal pair of Rhizomacoptidis and Artemisia capillaris in the treatment of chronic atrophic gastritis(CAG)based on the network pharmacology and molecular docking.Methods The active ingredients,targets and molecular structures of the TCM herbal pair of Rhizomacoptidis and Artemisia capillaris searched in the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP).The targets of CAG were searched in the GeneCards,the Comparative Toxicogenomics Database(CTD)and the Therapeutic Target Database(TTD).Using the Cytoscape,a protein-protein interaction(PPI)network and a drug-ingredient-target-disease network diagram were established by introducing the intersections of the targets of both the TCM herbal pair of Rhizomacoptidis and Artemisia capillaris,and CAG.The common active ingredients and targets were obtained by a cluster analysis on the two networks,which were further subjected to GO and KEGG enrichment analyses using the Database for Annotation,Visualization and Integrated Discovery(DAVID).Finally,molecular docking of the common active ingredients and targets was performed using the AutoDock and PyMOL.Results A total of 26 active ingredients were screened from the TCM herbal pair of Rhizomacoptidis and Artemisia capillaris,with 86 corresponding targets.A total of 639 targets of CAG were identified.Taking the intersection,a total of 38 targets were finally obtained.The core components are quercetin,isorhamnetin,β-sitosterol,etc Among them,interleukin 6(IL-6),tumor necrosis factor(TNF),Jun(Jun proto-oncogene)and others were above the average degree.GO enrichment analysis yielded 98 biological processes(BP),including the positive regulations of the transcription of RNA polymerase II promoter,nitric oxide biosynthesis and gene expressions;21 cell components(CC),including extracellular space,extracellular region and cell surface;and 18 molecular functions(MF),including enzyme binding,transcription

关 键 词：胃炎 慢性萎缩性 中药药理学 黄连 茵陈 

分 类 号：R573.32[医药卫生—消化系统]