基于网络药理学和分子对接探讨蒙药述达格-4治疗胃食管反流病的作用机制  

Exploring the mechanism of action of Mongolian medicine Shudage-4 in the treatment of gastroesophageal reflux disease based on network pharmacology and molecular docking

作　　者：陈晓梅 史圣华[1] 钱占红[1] 莫日根 刘派 CHEN Xiaomei;SHI Shenghua;QIAN Zhanhong;Mo Rigen;LIU Pai(Inner Mongolia Medical University,Inner Mongolia,Hohhot 010110;Inner Mongolia Autonomous Region Mental Health Center,Inner Mongolia,Hohhot 010010)

机构地区：[1]内蒙古医科大学,内蒙古呼和浩特010110 [2]内蒙古自治区精神卫生中心,内蒙古呼和浩特010010

出　　处：《中国民族医药杂志》2024年第8期62-67,共6页Journal of Medicine and Pharmacy of Chinese Minorities

基　　金：内蒙古科技计划项目(NO:2020SGG0732);内蒙古自然科学基金项目(NO:2020LH08033);内蒙古医科大学重点项目(YKD2021ZD005);内蒙古医科大学学科建设项目(YKD2023XK026);内蒙古医科大学优秀教学团队(NYJXTD202103);内蒙古医科大学教学质量工程项目教学名师(NYJXMS202202);内蒙古自治区卫生健康委医疗卫生科技计划(202202142);内蒙古自治区卫生健康委项目(2023SGGZ046);内蒙古自治区卫生健康科技计划项目(202201123);内蒙古自治区卫生健康科技计划项目(202202141)。

摘　　要：目的:以蒙医理论对蒙药述达格-4的认识为依据,通过网络药理学和分子对接技术探讨述达格-4治疗胃食管反流病的作用靶点及其可能的作用机制。方法:通过TCMSP数据库及文献搜集述达格-4的有效活性成分及对应的靶蛋白,通过Uniprot数据库将其转化成相应的基因名称;通过GeneCard、OMIM、DrugBank数据库中预测胃食管反流病的作用靶点;通过Venny 2.1.0获取交集靶点;STRING数据库获取蛋白质相互作用(PPI)网络后导入Cytoscape 3.9.1软件获取核心靶点;利用Metascape数据库,进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)生物通路富集分析;在微生信在线平台进行绘制GO富集分析柱状图、KEGG通路富集气泡图;Cytoscape 3.9.1软件构建“药材-活性成分-靶点”及“关键活性成分-核心靶点-通路”网络;Autodock对关键活性成分和核心靶点进行分子对接。结果:通过限制口服吸收利用度(OB)、药物相似性(DL)的数值,共筛选出23种活性成分,作用于TNF,EGFR,PTGS2,PPARG和CCND1等关键靶点。通过调节PI3K-Ak、细胞衰老等信号通路治疗胃食管反流。分子对接显示,活性成分与核心靶点具有较好的结合活性,其中谷甾醇与核心靶点结合的最好。结论:本研究初步揭示了述达格-4中的活性成分高良姜素、山奈素、谷甾醇等能作用于多个靶点和调控多条通路来抑制炎症反应,对胃食管反流可能具有治疗作用。Objective:Based on the understanding of Mongolian medicine theory of theory,to explore the action target and possible mechanism of Shudage-4 in the treatment of gastroesophageal reflux disease by network pharmacology and molecular docking technology.Methods:through TCMSP database and literature collection of Shudage-4,the effective active ingredient and the corresponding target protein,by transforming it into a corresponding Uniprot database gene name;GeneCard,OMIM and DrugBank were used to predict the targets of gastroesophageal reflux disease.The intersection targets were obtained by Venny2.1.0.STRING after the database to get protein interaction(PPI)networks into Cytoscape 3.9.1 software for the core targets;Gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed using Metascape database.The GO enrichment analysis bar diagram and KEGG pathway enrichment bubble diagram were drawn on the wechat online platform.Cytoscape 3.9.1 software was used to construct the"medicinal material-active ingredient-target"and"key active ingredient-core target-pathway"networks.Autodock performs molecular docking of key active ingredients and core targets.Results:by limiting the oral absorption and utilization of degrees(OB),drugs(DL)of numerical similarity,a total of23 kinds of active ingredients,acting on TNF,EGFR,PTGS2,PPARG and CCND1 key targets.By regulating PI3K-Ak,cell senescence and other signaling pathways to treat gastroesophageal reflux.Molecular docking showed that the active ingredients had good binding activity to the core targets,and sitosterol was the best binding to the core targets.Conclusion:The present study reveals that the active ingredients of Shudage-4,such as galangin,kaempferin and sitosterol,can inhibit inflammatory response by acting on multiple targets and regulating multiple pathways,and may have therapeutic effects on gastroesophageal reflux.

关 键 词：胃食管反流病 述达格-4 网络药理学 分子对接 

分 类 号：R29[医药卫生—民族医学]