基于体外透皮成分分析的靶向网络药理学结合分子对接的儿泻康贴膜药效物质基础及作用机制研究  

Targeted network pharmacology based on analysis of transdermal constituents in vitro combined with molecular docking to study substance basis and mechanism of Erxiekang Emplastra

作　　者：王甜[1] 宋紫腾 罗春 郝艳琦 朱加华 余彩霞 许浚[2,3] 张铁军 刘昌孝[2] WANG Tian;SONG Ziteng;LUO Chun;HAO Yanqi;ZHU Jiahua;YU Caixia;XU Jun;ZHANG Tiejun;LIU Changxiao(Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine,National&Local United Engineering Laboratory of Modern Preparation and Quality Control Technology of Traditional Chinese Medicine,Tianjin Key Laboratory of Quality Marker of Traditional Chinese Medicine,Tianjin Institute of Pharmaceutical Research,Tianjin 300462,China;Heguang Chinese Medicine Technology(Tianjin)Co.,Ltd.,Tianjin 300462,China;Shanghai Children's Nutrition Center,Shanghai 201403,China)

机构地区：[1]天津中医药大学,天津301617 [2]天津药物研究院药物成药性评价与系统转化全国重点实验室,中药现代制剂与质量控制技术国家地方联合工程实验室,天津市中药质量标志物重点实验室,天津300462 [3]和光中药科技(天津)有限公司,天津300462 [4]上海儿童营养中心,上海201403

出　　处：《药物评价研究》2024年第10期2261-2276,共16页Drug Evaluation Research

基　　金：国家自然科学基金委员会重点项目(81830111)。

摘　　要：目的 通过高效液相色谱-四极杆-飞行时间质谱(HPLC-Q-TOF-MS/MS)分析儿泻康贴膜体外透皮接收液的化学成分,结合网络药理学和分子对接技术初步预测其治疗小儿腹泻、腹痛的药效物质基础及作用机制。方法 采用HPLC-QTOF-MS/MS于正、负离子模式下扫描,确认儿泻康贴膜透皮化学成分。选取19个主要活性成分为研究对象,利用Swiss Target prediction数据库收集化合物潜在作用靶点;通过GeneCards、OMIM、Drugbank数据库获取小儿腹泻、腹痛相关疾病靶点;借助String 12.0网络分析平台,获得活性成分与疾病交集靶点的蛋白质-蛋白质相互作用(PPI)网络,从而筛选出核心靶点;利用Omicsbean在线分析平台对交集靶点进行基因本体(GO)功能分析和京都基因与基因组百科全书(KEGG)通路富集分析,进一步通过Cytoscape3.9.1软件构建网络图;运用Schr?dinger2020 Maestro12.4软件将10个主要活性成分与15个核心靶点进行分子对接,验证其结合能力。结果 儿泻康贴膜体外透皮接收液共鉴定出90个成分,包括生物碱类、黄酮类、有机酸类、苯丙素类、三萜类、苦味素及其他类;选取的19个活性成分治疗小儿腹泻、腹痛的潜在作用靶点共260个,经PPI网络分析筛选出肿瘤蛋白p53(TP53)、信号传导及转录激活蛋白3(STAT3)、表皮生长因子受体(EGFR)、丝氨酸/苏氨酸蛋白激酶1(AKT1)等15个核心靶点;KEGG通路富集共得到166条通路,筛选出与疾病密切相关的通路共90条,包括磷脂酰肌醇-3-激酶-蛋白激酶B信号通路、丝裂原活化蛋白激酶信号通路、神经营养素信号通路、白细胞介素17信号通路等重要信号通路。分子对接结果显示,儿泻康贴膜中10个主要活性成分与15个核心靶点蛋白间结合能力较强,能形成稳定的复合物。结论 通过HPLC-Q-TOF-MS/MS获得儿泻康贴膜体外透皮成分,结合网络药理学和分子对接技术初步确定了儿泻康贴膜发挥多成分�Objective To analyze the chemical components of the transdermal receiving solution of Erxiekang Emplastra in vitro by HPLC-Q-TOF-MS/MS,and to preliminarily predict the pharmacodynamic material basis and mechanism of its efficacy in treating children's wind-cold diarrhea by network pharmacology and molecular docking technology.Methods HPLC-Q-TOF-MS/MS was used to scan in positive and negative ion mode to confirm the transdermal chemical components of Erxiekang Emplastra.A total of 19 main active components were selected as the research objects,and the potential targets of the compounds were collected by Swiss Target prediction database.The targets of diseases related to wind-cold diarrhea in children were obtained through GeneCards,OMIM and Drugbank databases.STRING network analysis platform was used to obtain the protein-protein interaction(PPI)network of active ingredients and disease targets was obtained,so as to screen out the core targets.On-line analysis platform of Omicsbean was used to analyze the function of gene ontology(GO)and the pathway enrichment of Kyoto Gene and Genome Encyclopedia(KEGG),and then the network diagram was constructed by Cytoscape software.Schrodinger2020 Maestro12.4 software was used to perform molecular docking between 10 main active ingredients and 15 core targets to verify their binding ability.Results A total of 90 components were identified from the transdermal receiving solution of Erxiekang Emplastra in vitro,including alkaloids,flavonoids,organic acids,phenylpropanoids,triterpenoids,picrosins and others.There were 260 potential targets of 19 active ingredients in the treatment of wind-cold diarrhea in children,and 15 core targets,such as tumor protein p53(TP53),signal transduction and transcription activating protein 3(STAT3),epidermal growth factor receptor(EGFR)and serine/threonine protein kinase 1(AKT1)were screened out by PPI network analysis.A total of 166 pathways were obtained by enrichment of KEGG pathway,and 90 pathways closely related to the disease were screened ou

关 键 词：儿泻康贴膜 体外透皮成分 网络药理学 分子对接 桂皮醛 丁香酚 乙酸丁香酚酯 柠檬苦素 吴茱萸碱 胡椒碱 吴茱萸次碱 

分 类 号：R285.5[医药卫生—中药学]