摘要
目的:通过网络药理学和分子对接技术探究半夏厚朴汤对胃食管反流病(GERD)和抑郁症"异病同治"的作用机制。方法:应用TCMSP数据库检索半夏厚朴汤中相关化学成分和对应靶点,通过GeneCards数据库获取GERD和抑郁症的作用靶点。对药物作用靶点和疾病基因取交集以获得共有靶点,并构建"中药-化合物-靶点"作用网络。运用STRING11.0数据库构建共有靶点的蛋白质互作网络,并导入Cytoscape3.6.0使网络可视化,对共有靶点进行GO和KEGG通路富集分析。运用Auto Dock Vina软件将活性化合物与核心靶点蛋白进行分子对接。结果:以OB≥30%和DL≥0.18为条件进行筛选,共得到半夏厚朴汤中49个化合物作用于124个潜在靶点。在GeneCards数据库中检索得到GERD靶点2960个,抑郁症靶点10105个,两者与药物靶点取交集得到76个共有靶点。GO功能富集分析得到分子功能19个、生物过程1个;KEGG富集分析显示这些靶点在PI3K-AKT、IL-17、凋亡、HIF-1等信号通路中发挥着重要作用。将这些关键通路中的靶点导入STRING11.0数据库构建蛋白质网络,用Cytoscape3.6.0进行可视化分析并统计关键作用靶点。根据度值(Degree)筛选得出MAPK1、AKT1、IL-6这3个关键靶点。分子对接结果显示,这3个靶点与木犀草素、黄芩素、β-胡萝卜素具有强烈的结合活性。结论:半夏厚朴汤"异病同治"GERD和抑郁症的机制主要涉及PI3K-AKT、IL-17、凋亡、HIF-1等信号通路,为进一步实现新药靶点研发及临床应用拓展提供参考依据。
Objective:To explore the mechanism of Banxia Houpo Decoction treating gastroesophageal reflux disease(GERD)and depressive disorder with concept of"treating different diseases with same treatment",according to network pharmacology and molecular docking technology.Methods:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database was uses to retrieve all the chemical components and corresponding targets related to Chinese medicine in Banxia Houpo Decoction,and the targets of GERD and depressive disorder were obtained through Gene Cards database.The intersection of drug targets and disease genes was obtained to get a common target,and construct a"Chinese medicine-compound-target"action network.The STRING11.0 database was applied to construct a protein interaction network with common targets,and the protein interaction network with common targets were imported into Cytoscape 3.6.0 for visualization.The common targets were analyzed by perform gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)analysis.Molecular docking of active compounds with core target proteins was carried out by using Auto Dock Vina software.Results:With oral bioavailability(OB)≥30%and drug-like index(DL)≥0.18 as the screening conditions,a total of 49 compounds in Banxia Houpo Decoction acted on 124 potential targets.In the Genecards database,2960 GERD targets and 10105 depressive disorder targets were retrieved.The intersection of GERD targets,depressive disorder targets and drug targets resulted in 76 common targets.GO function enrichment analysis revealed 19 molecular functions and a biological process.KEGG enrichment analysis showed that these targets play an important role in PI3 K-AKT,IL-17,apoptosis,HIF-1 and other signaling pathways.The targets in these key pathways were imported into the STRING11.0 database to construct a protein network,and Cytoscape3.6.0 was used for visual analysis and statistics of key targets.According to the degree value(Degree),three key targets,MAPK1,AKT1,and
作者
何美君
贾博
白光
HE Mei-jun;JIA Bo;BAI Guang(Graduate School,Liaoning University of Traditional Chinese Medicine,Shenyang Liaoning 110847,China;Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine,Beijing 100700,China;Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang Liaoning 110033,China.)
出处
《中医药导报》
2021年第8期138-143,共6页
Guiding Journal of Traditional Chinese Medicine and Pharmacy
基金
第三届国医大师传承工作室及全国名中医传承工作室建设项目[辽中医药函字(2018)76号]
北京医卫健康公益基金会-医学科学研究基金资助项目(YWJKJJHKYJJ-A220)。
关键词
胃食管反流病
抑郁症
半夏厚朴汤
异病同治
网络药理学
gastroesophageal reflux disease
depressive disorder
Banxia Houpo Decoction
treating different diseases with same method
network pharmacology
