摘要
目的基于网络药理学探讨麻杏石甘汤防治慢性支气管炎的潜在作用机制。方法利用TCMSP及TCMID数据库收集麻杏石甘汤活性成分及靶点。使用GeneCards及OMIM数据库筛选慢性支气管炎相关基因并与麻杏石甘汤活性成分靶基因取交集,利用STRING网站构建蛋白互作网络(PPI网络),借助Reactome数据库对交集靶点进行生物过程分析及Omicshare平台进行KEGG代谢通路分析,并使用Cytoscape软件构建"成分-靶点-通路"网络,并进行网络拓扑学分析筛选核心靶点及核心通路,最后将从PDB数据中获得的核心靶标蛋白晶体结构导入Autodock软件,对活性成分和核心靶标蛋白进行虚拟分子对接分析。结果利用TCMSP及TCMID数据库共收集筛选得到麻杏石甘汤51个潜在活性成分和891个潜在靶点,与慢性支气管炎相关基因取交集后得到13个重合靶点。Reactome数据库分析表明,13个潜在作用靶点主要涉及免疫系统、信号转导、基因表达、细胞对外部刺激反应等多个生物过程;KEGG富集分析结果表明,13个交集靶点共涉及63条通路,靶点富集数量最多的通路为流体剪切应力与动脉粥样硬化、癌症途径。麻杏石甘汤防治慢性支气管炎的"成分-靶点-通路"网络共有116个节点、254条边,平均节点度值为4.38、平均介数中心值为219.3、平均接近中心值为0.355。其中,MAPK14、RELA、TGF-β1基因是麻杏石甘汤有效成分治疗慢性支气管炎的核心作用靶点。流体剪切应力和动脉粥样硬化信号通路、糖尿病患者AGE-RAGE信号通路和松弛素信号通路等8个通路是麻杏石甘汤有效成分治疗慢性支气管炎的核心信号通路。分子对接结果表明,麻杏石甘汤中的活性成分与关键靶点具有良好的结合能力。结论研究基于网络药理学方法及分子对接预测了麻杏石甘汤用于治疗慢性支气管炎的主导化合物成分、核心靶点和核心信号通路,为临床药物治疗提供了新思路和新方向。
Objective To explore the potential mechanism of Maxing Shigan Decoction(麻杏石甘汤)in the prevention and treatment of chronic bronchitis based on network pharmacology.Methods The active components and targets of Maxing Shigan Decoction were collected by TCMSP and TCMID database.Chronic bronchitis related genes were screened by GeneCards and OMIM database and intersected with target genes of active components of Maxing Shigan Decoction.Protein internetwork(PPI network)was constructed by STRING website.Biological process analysis of intersection targets was carried out with Reactome database and KEGG metabolic pathway analysis was carried out on Omicshare platform“.Component-target-pathway”network was constructed by Cytoscape software,and network topology analysis was carried out to screen core targets and core pathways.Finally,the crystal structure of the core target protein obtained from the PDB data was imported into the Autodock software to carry out virtual molecular docking analysis of the active components and the core target protein.Results A total of 51 potential active components and 891 potential targets were collected using the TCMSP and TCMID databases,and 13 coincidence targets were obtained after intersecting with genes related to chronic bronchitis.Reactome database analysis showed that 13 potential targets were mainly involved in many biological processes such as immune system,signal transduction,gene expression and cell response to external stimuli,while KEGG enrichment analysis showed that a total of 63 pathways were involved in 13 intersection targets,and the pathways with the largest number of target enrichment were fluid shear stress,atherosclerosis and cancer pathway.The“component-target-pathway”network of Maxing Shigan Decoction for the prevention and treatment of chronic bronchitis had a total of 116 nodes and 254 edges,with an average node value of 4.38,an average intermediate central value of 219.3 and an average close to central value of 0.355.Among them,MAPK14,RELA and TGF-β1 genes were the core targets of the effective components of Maxing Shigan Decoction in the treatment of chronic bronchitis.Eight pathways,such as fluid shear stress and atherosclerosis signal pathway,AGERAGE signal pathway and relaxin signal pathway in diabetic patients,were the core signal pathways of effective components of Maxing Shigan Decoction in the treatment of chronic bronchitis.The results of molecular docking showed that the active components in Maxing Shigan Decoction had good binding ability with key targets.Conclusion Based on the method of network pharmacology and molecular docking,this study predicted the main compound components,core targets and core signal pathways of Maxing Shigan Decoction in the treatment of chronic bronchitis,which provided new ideas and new directions for clinical drug therapy.
作者
邓丽婵
舒安镕
潘锦媚
蒋向辉
DENG Lichan;SHU Anrong;PAN Jinmei;JIANG Xianghui(Huaihua University,Huaihua 418008,Hunan,China;Key Laboratory of Hunan Province for Study and Utilization of Ethnic Medicinal Plant Resources,Huaihua 418008,Hunan,China)
出处
《辽宁中医药大学学报》
CAS
2021年第10期172-181,共10页
Journal of Liaoning University of Traditional Chinese Medicine
基金
湖南省大学生创新训练项目(1951)
湖南省教育厅重点资助项目(19A390)
关键词
麻杏石甘汤
慢性支气管炎
网络药理学
作用机制
核心靶点
Maxing Shigan Decoction(麻杏石甘汤)
chronic bronchitis
network pharmacology
mechanism of action
core targes
