基于网络药理学和分子对接技术探析除湿解毒饮治疗银屑病的作用机制  

Exploring the mechanisms of Chushi Jiedu Yin in the treatment of psoriasis based on network pharmacology and molecular docking

作　　者：周兢兢 张文静 ZHOU Jingjing

机构地区：[1]重庆市中医院,重庆400000 [2]中国人民解放军总医院第五医学中心,北京100000

出　　处：《中医临床研究》2023年第1期14-21,共8页Clinical Journal Of Chinese Medicine

基　　金：成都中医药大学2022年度“杏林学者”学科人才科研提升计划项目(YYZX2022133)。

摘　　要：目的:利用网络药理学和分子对接技术探析除湿解毒饮治疗银屑病的作用靶点、信号通路及分子机制,为后期进一步实验研究提供理论依据。方法:采用中药系统药理学数据库与分析平台(TCMSP)筛选出除湿解毒饮中黄芩、苦参等有效成分和靶点基因;利用Genecards数据库、OMIM数据库、PharmGkb数据库等检索银屑病的相关基因;运用R软件将药物靶点与银屑病相关基因取交集,利用交集基因在Cytoscape中构建中药复方调控网络;在STRING数据库中在线绘制蛋白质-蛋白质相互作用网络,并用插件CytoNCA查找调控网络核心基因;运用R软件对核心靶点基因进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。使用Vina软件将主要药物活性成分槲皮素、汉黄芩素、贯叶金丝桃素、柚皮素、山柰酚、甘草查尔酮A分别与靶点丝裂原活化蛋白激酶(Mitogen-Activated Protein Kinase,MAPK)3、MAPK8、白细胞介素-8(Chemokine 8,CXCL8)、信号转导因子和转录激活因子3(Signal Transducer and Activator of Transcription 3,STAT3)进行分子对接验证。结果:通过口服利用度和类药性筛选得到除湿解毒饮的化合物293种、药物靶点250个,其中与银屑病相关的靶点基因121个,利用Cytoscape及CytoNCA插件4次筛选得到核心靶基因7个。GO富集分析获得分子功能2318条,其中生物过程2108条、细胞组成45条、分子功能165条。KEGG富集分析获得通路174条。槲皮素、汉黄芩素、贯叶金丝桃素、柚皮素、山柰酚、甘草查尔酮A是除湿解毒饮的主要活性成分;CXCL8、MAPK3、MAPK8、STAT3、JUN原癌基因(Jun Proto-Oncogene,JUN)、表皮生长因子(Epidermal Growth Factor,EGF)、MAPK1等为主要作用靶标。将药物活性成分与MAPK3、MAPK 8、CXCL8、STAT3进行分子对接,结果显示药物小分子配体与核心靶点之间能够较好结合,涉及Th17、MAPK、白细胞介素-17(Interleukin-17,IL-17)、c-Jun氨基末端�Objective:This study is to explore the targets,signal pathways and molecular mechanism of Chushi Jiedu Yin(除湿解毒饮)in the treatment of psoriasis based on network pharmacology and molecular docking technology.Methods:First,the active ingredients and target genes of Huangqin(Radix Scutellariae),Kushen(Radix Sophorae Flavescentis)and so on were selected by TCM systematic pharmacology database and analysis platform(TCMSP).Using the Genecards database,OMIM database,PharmGkb database,TTD database,and Drug Bank database,the genes related to psoriasis were retrieved.Secondly,R software was used to intersect the drug target and psoriasis-related genes,and the intersection genes were used to construct the regulation network of TCM compound in Cytoscape.Meanwhile,We mapped the protein interaction network online in the STRING database and searched the hub genes of the regulatory network using the CytoNCA plug-in.Then,the hub target genes were enriched by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis by R software.Last,Vina software was used to conduct molecular docking verification of quercetin,wogonin,hyperforin,naringenin,kaempferol,licochalcone A with the targets of MAPK 3,MAPK 8,CXCL8,STAT3,respectively.Results:We obtained 293 active compounds and 250 drug targets of Chushi Jiedu Yin through the TCMSP database according to oral bioavailability and drug-likeness criteria.There were 121 target genes associated with psoriasis.Then we used Cytoscape and CytoNCA plug-in for 4 times of screening and got 7 hub target genes finally by GO and KEGG enrichment analysis,we obtained 2318 molecular functions,including 2108 biological processes,45 cellular components,165 molecular functions and 174 main pathways associated with psoriasis.Quercetin,wogonin,hypericin,naringin,kaempferol and glycyrrhizone A were the main active components of dehygness-jiedu drink,and CXCL8,MAPK3,MAPK8,STAT3,JUN,EGF and MAPK1 were the main targets.Molecular docking results showed that small molecule ligands c

关 键 词：网络药理学 银屑病 分子对接 分子机制 

分 类 号：R758.63[医药卫生—皮肤病学与性病学]