基于网络药理学探讨浙贝母-海螵蛸药对治疗胃食管反流病作用机制  

Exploration on Action Mechanism of Fritillariae Thunbergii Bulbus-Sepiae EndoconchaDrug Pair for Gastroesophageal Reflux Disease Based on Network Pharmacology

作　　者：刘颖盈 苏桂芳 郑欢 吴皓萌[2,3,4] 秦书敏 黄绍刚 LIU Yingying;SU Guifang;ZHENG Huan;WU Haomeng;QIN Shumin;HUANG Shaogang(Dongguan Hospital of Guangzhou University of Chinese Medicine,Dongguan Guangdong 523000,China;The Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou Guangdong 510120,China;Yang Chunbo Academic Experience Inheritance Studio,Guangdong Provincial Hospital of Chinese Medicine,Guangzhou Guangdong 510120,China;Guangdong Provincial Key Laboratory of Clinical Research of Traditional Chinese Medicine Syndromes,Guangzhou Guangdong 510120,China;Huang Shaogang Dongguan famous Chinese medicine studio,Dongguan Guangdong 523000,China)

机构地区：[1]广州中医药大学东莞医院,广东东莞523000 [2]广州中医药大学第二附属医院,广东广州510120 [3]广东省中医院杨春波学术经验传承工作室,广东广州510120 [4]广东省中医证候临床研究重点实验室,广东广州510120 [5]东莞市黄绍刚名中医工作室,广东东莞523000

出　　处：《新中医》2024年第13期214-222,共9页New Chinese Medicine

基　　金：东莞市名中医工作室建设项目(东卫涵号[2021]134号);东莞市社会发展科技项目(20221800900072)。

摘　　要：目的:基于网络药理学探讨浙贝母-海螵蛸药对治疗胃食管反流病(GERD)的作用机制。方法:通过中药系统药理学数据库与分析平台(TCMSP)、BATMAN-TCM、中药与有效成分、本草组鉴-HERB等数据库及相关文献筛选浙贝母-海螵蛸的活性成分,使用Swiss ADME与SwissTargetPrediction平台对活性成分靶点进行预测。利用GeneCards、DisGeNET、Drugbank筛选GERD的作用靶点,通过Jvenn平台取浙贝母-海螵蛸与GERD的交集靶点,将交集靶点上传STRING11.0数据库,运用Cytoscape3.7.1软件构建蛋白互作网络图,获取浙贝母-海螵蛸药对治疗GERD的核心靶点;借助Metascape数据库对核心靶点进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)通路富集分析;采用AutoDock工具将药对中的关键成分与核心靶点进行分子对接验证。结果:共筛选出浙贝母-海螵蛸药对活性成分28个,药物靶点536个,GERD靶点1997个。浙贝母-海螵蛸药对的核心活性成分有贝母素乙、浙贝丙素、苦鬼臼毒素等;浙贝母-海螵蛸药对治疗GERD的核心靶点有丝氨酸/苏氨酸蛋白激酶(AKT1)、丝裂原活化蛋白激酶(MAPK)1、磷脂酰肌醇3-激酶催化亚基δ(PIK3CD)、表皮生长因子(EGFR)、原癌基因(JUN)等。浙贝母-海螵蛸药对治疗GERD主要作用于神经活性配体-受体相互作用、磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)、MAPK及癌症等信号通路。分子对接发现药物核心活性成分浙贝丙素、贝母素乙与AKT1等靶点结合活性较高。结论:浙贝母-海螵蛸药对中贝母素乙、浙贝丙素、苦鬼臼毒素等成分能作用于AKT1、EGFR等靶点治疗GERD,其作用机制与调节神经活性配体-受体相互作用、PI3K/Akt信号、MAPK信号通路等多条信号通路有关。Objective:To explore the action mechanism of Fritillariae Thunbergii Bulbus-Sepiae Endoconcha drug pair for gastroesophageal reflux disease(GERD)based on network pharmacology.Methods:The active components of Fritillariae Thunbergii Bulbus-Sepiae Endoconcha were screened through Traditional Chinese Medicines Systems Pharmacology Platform(TCMSP),BATMAN-TCM,Chinese medicine and active ingredients,Ben Cao Zu Jian-HERB databases and related literature.SWISS ADME and SwissTargetPrediction platform were used to predict active ingredient targets.GeneCards,DisGeNET and Drugbank were used to screen the targets of GERD;the intersection targets of Fritillariae Thunbergii Bulbus-Sepiae Endoconcha drug pair and GERD were obtained through Jvenn Platform,and the intersection targets were uploaded to STRING11.0 database.Cytoscape3.7.1 software was used to construct protein interaction network diagram to obtain the core targets of Fritillariae Thunbergii Bulbus-Sepiae Endoconcha drug pair for GERD treatment;Genetic Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for core targets using Metascape database;AutoDock tools was used to verify the molecular docking between key components in drug pairs and core targets.Results:A total of 28 active ingredients of Fritillariae Thunbergii Bulbus-Sepiae Endoconcha durg pairs,536 medicine targets and 1997 GERD targets were screened out.The core active components of Fritillariae Thunbergii Bulbus-Sepiae Endoconcha drug pairs included Peiminine,Zhebeirine,Picropodophyllin,etc.;the core targets of Fritillariae Thunbergii Bulbus-Sepiae Endoconcha drug pairs in the treatment of GERD included serine/threonine-protein kinase(AKT1),mitogen-activated protein kinase(MAPK)1,phosphatidylinosiol 3-kinase catalytic domainδ(PIK3CD),epidermal growth factor(EGFR),proto-oncogene(JUN)and so on.Fritillariae Thunbergii Bulbus-Sepiae Endoconcha medicine pairs mainly act on neuroactive ligand-receptor interaction,phosphatidylinositol 3 kinase(PI3K)/protein kin

关 键 词：胃食管反流病 浙贝母-海螵蛸 网络药理学 作用机制 

分 类 号：R57[医药卫生—消化系统]