基于网络药理学和分子对接技术探索小儿化积治疗小儿哮喘的作用机制

Action mechanism of Xiaoer-huaji-zhike-fang in the treatment of childhood asthma based on network pharmacology and molecular docking

目的:旨在探讨小儿化积止咳方治疗小儿哮喘(Childhood asthma)的物质基础及作用机制。方法:通过TCMSP、SwissTargetPrediction、DisGeNET数据库获取药物成分靶点与疾病靶点;利用Cytoscape 3.9.0软件构建中药-成分-靶点网络;对药物疾病交集靶点做蛋白蛋白互作分析,并筛选出10个Hub genes进行GO功能、KEGG通路富集分析以及分子对接。结果:获得药物与疾病的交集靶点62个,其中10个Hub genes主要参与防御反应的调节、免疫球蛋白的调节、免疫效应过程的正向调节等生物学过程,调控IL-17、TNF、T细胞受体等信号通路。分子对接结果显示其中3个关键靶点(IL6、TNF、MMP9)可以与方子中的棕榈酸甲酯、木犀草素、异甘草黄苷、异甘草醇、芹菜素等18种化合物结合。结论:小儿化积止咳方主要通过靶向结合IL6、TNF、MMP9等靶点调控IL-17、TNF、T细胞受体等信号通路而发挥平喘功效。

To investigate the material basis and action mechanism of Xiaoer-huaji-zhike-fang in the treatment of childhood asthma,drug component targets and disease targets were obtained through TCMSP,SwissTargetPrediction and DisGeNET databases.Cytoscape 3.9.0 software was used to build the drug-ingredient-target network.Protein interaction analysis was performed on the drug-disease intersection targets,and 10 Hub genes were screened for GO function and KEGG pathway enrichment analysis,as well as molecular docking.62 drug-disease intersection targets were obtained,of which 10 Hub genes were mainly involved in biological processes such as the regulation of defense responses,the regulation of immunoglobulins,and the positive regulation of immune effect processes,as well as the regulation of signaling pathways such as IL-17,TNF,and T cell receptors.The molecular docking results showed that three of the key targets(IL6,TNF,MMP9)had strong affinity with 18 compounds in the drug,including methyl palmitate,luteolin,isoliquilicorbidilin,isoglyrrhizinol,apigenin,etc.In conclusion,Xiaoer-huaji-zhike-fang treats asthma through targets such as IL6,TNF,MMP9 to regulate signaling pathways such as IL-17,TNF,and T cell receptors.