基于网络药理学和分子对接术探讨固本防哮饮治疗小儿哮喘的作用机制

Mechanism of gubenfangxiaoyin drinking in the treatment of infantile asthmaprevention by network pharmacology and molecular docking

目的基于网络药理学与分子对接技术探讨固本防哮饮治疗小儿哮喘的作用机制。方法通过TCMSP数据库及文献检索补充收集药物化学成分信息;在PubChem、SwissTargetPrediction、GeneCards等数据库收集中药化学成分及小儿哮喘疾病靶点。借助Cytoscape 3.7.2软件绘制“药物-活性成分-靶点”图。基于String数据库构建蛋白质相互作用网络图并通过Cytoscape 3.7.2进行分析。利用Metascape数据库对作用靶点进行GO和KEGG通路分析。结果共筛选出固本防哮饮238个有效成分及其对应的697个主要靶点,小儿哮喘疾病靶点1052个,二者共同靶点242个,富集分析发现共同靶点主要参与MAPK级联调节、炎症反应等生物过程,以及钙信号通路、cAMP信号通路、AGE-RAGE信号通路、cGMP-PKG信号通路等。分子对接结果显示,黄芪的活性成分(5′-hydroxyiso-muronulatol-2′,5′-di-O-glucoside)与SRC、TP53、IL-6靶点对接良好。实验验证发现,固本防哮饮能够下调IL-6、SRC、TP53等蛋白的表达。结论固本防哮饮可能通过5′-hydroxyiso-muronulatol-2′,5′-di-O-glucoside,槲皮素、异鼠李素、山奈酚等活性成分作用于STAT3、SRC、AKT1、TP53、TNF、MAPK3、IL-6等靶点,参与调控小儿哮喘的钙信号通路、cAMP信号通路、AGE-RAGE信号通路、cGMP-PKG信号通路等,降低MAPK级联反应、炎症反应等,发挥防治哮喘的作用。

Aim To explore the mechanism of pediatric asthma based on network pharmacology and molecular docking technology.Methods Through TCMSP database,the chemical information and the targets of TCM chemical components and pediatric asthma targets in PubChem,SwissTargetPrediction and GeneCards were collected,and the intersection gene,namely the target gene of pediatric asthma was used.The“Drug-active ingredient-target”map was plotted with the Cytosacape 3.7.2 software.Protein interaction network maps were constructed based on the String database and analyzed by Cytoscape 3.7.2.GO and KEGG pathway analysis of acting targets using the Metascape database and bubbles were plotted on the Omicshare platform.Results A total of 238 active components and 11 corresponding 697 main targets were selected,1052 pediatric asthma disease target targets and 242 common targets were selected.Enrichment analysis found that common targets were primarily involved in biological processes such as MAPK cascade regulation and inflammatory response,as well as calcium signaling pathway,cAMP signaling pathway,AGE-RAGE signaling pathway,cGMP-PKG signaling pathway,etc.Molecular docking results showed that the active components of Astragalus(5′-hydroxyiso-muronulatol-2′,5′-di-O-glucoside)docked well with the SRC,TP53,and IL-6 targets.We proved that anti-resistant drinking could down-regulate the expression of IL-6,SRC and TP53.Conclusions Gubenfangxiaoyin drinking may be involved in the regulation of the STAT3,SRC,AKT1,TP53,TNF,MAPK3,TP53,TNF,MAPK3 and IL6 and other targets,involved in the regulation of calcium-cAMP signaling pathway in childhood asthma,AGE-RAGE signaling pathway,cGMP-PKG signaling pathway,reduce the MAPK cascade,inflammatory response,etc,and play a role in the prevention and treatment of asthma.