基于网络药理学的砂仁抗溃疡性结肠炎机制研究  

Mechanism of the anti-UC effect of Fructus Amomi based on network pharmacology

作　　者：柴常伟 张海婧[1] 吴练秋[1] CHAI Chang-wei;ZHANG Hai-jing;WU Lian-qiu(Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,北京100050

出　　处：《药学学报》2022年第11期3345-3355,共11页Acta Pharmaceutica Sinica

基　　金：中国医学科学院医学与健康科技创新工程国家医学科技健康战略平台与体系建设专项(2022-I2M-2-002)。

摘　　要：应用网络药理学方法预测砂仁抗溃疡性结肠炎(ulcerative colitis,UC)的活性成分和作用机制。首先通过体内动物实验验证中药砂仁的抗UC活性,动物福利和实验过程均遵循中国医学科学院药物研究所实验动物伦理委员会的规定。进一步应用TCMSP、PubChem数据库及文献调研获取砂仁的活性成分,采用SwissTargetPrediction、GeneCards和TTD数据库预测活性成分抗UC的潜在作用靶点。使用String数据库构建蛋白互作关系网络;Cytoscape软件将成分-作用靶点网络可视化并进行拓扑学分析;Metascape平台进行GO功能和KEGG通路富集分析;Sybyl-X软件将砂仁关键活性成分与部分核心靶蛋白进行分子对接。筛选共获得12种活性成分、189个砂仁抗UC靶点,富集分析后得到227个GO相关条目、168条相关信号通路。分子对接结果证明,砂仁主要活性成分与JAK受体家族具有较好的亲和力,体内验证结果表明砂仁能调控JAK/STAT信号通路。以上结果证明,砂仁及其提取物可能通过JAK/STAT信号通路发挥抗UC作用。We predicted the anti-ulcerative colitis(UC)mechanism of Fructus Amomi based on network pharmacology.The anti-UC activity of Fructus Amomi were investigated by in vivo animal experiment,and the active components of Fructus Amomi were obtained through TCMSP,PubChem database and literature research.Animal welfare and experimental procedures follow the regulations of the Animal Ethics Committee of Institute of Materia Medica of Chinese Academy of Medical Sciences.The potential targets of the active components and UC were predicted by SwissTargetPrediction,GeneCards and TTD databases.The protein-protein interaction(PPI)network was constructed by String database and Cytoscape software was used to construct a visual network of active component-disease target and perform topological analysis.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed using Metascape platform.The molecular docking of key components and core targets was carried out by Sybyl X software.We screened out a total of 12 active components and 189 disease-component overlapping targets.Enrichment analyses obtained 227 related GO items and 168 signaling pathways.According to the results of molecular docking,most active components of Fructus Amomi showed good affinity with the JAKs receptor family.Furthermore,Western blot results verified that Fructus Amomi could effectively inhibit JAK/STAT signaling pathway,indicating that Fructus Amomi might exert the anti-UC activity by regulating JAK/STAT signaling pathway.

关 键 词：砂仁 溃疡性结肠炎 网络药理学 作用机制 JAK/STAT 

分 类 号：R966[医药卫生—药理学]