基于网络药理学探讨泻白散治疗小儿喘息性支气管炎的作用机制

Mechanism of action of Xiebai powder in treatment of pediatric asthmatic bronchitis:A study based on network pharmacology

目的:基于网络药理学方法分析中医名方泻白散治疗小儿喘息性支气管炎的作用机制。方法:通过TCMSP数据库获取泻白散的有效成分及其作用蛋白-基因靶点,通过GeneCards、Drug Bank等数据库获取主要疾病靶点。利用STRING数据平台进行蛋白质-蛋白质相互作用(PPI)网络分析,运用Metascape数据平台进行基因本体(GO)功能与京都基因与基因组百科全书(KEGG)通路富集分析。采用Cytoscape 3.8.0软件建立“中药-共同靶点-主要通路”网络。结果:获得泻白散治疗小儿喘息性支气管炎的主要活性成分为山柰酚、槲皮素、甘草查尔酮A、柚皮素、18α-羟基甘草酸等;其核心靶点为丝裂原活化蛋白激酶1(MAPK1)、丝裂原活化蛋白激酶3(MAPK3)、核因子κ-B激酶亚基β抑制剂(IKBKB)、白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)、丝裂原活化蛋白激酶8(MAPK8)、半胱天冬酶-3(CASP3)和丝裂原活化蛋白激酶14(MAPK14)等。通过分子对接验证,大部分靶点与化合物都有较好的结合效果。靶点富集通路包括白细胞介素-17信号通路(IL-17 signaling pathway)、肿瘤坏死因子信号通路(TNF signaling pathway)和缺氧诱导因子-1信号通路(HIF-1 signaling pathway)等诸多炎症通路。结论:泻白散可通过多靶点、多通路的互相作用,降低喘息性支气管炎的炎症风暴,并缓解气道痉挛。本研究结果为泻白散治疗小儿喘息性支气管炎提供了理论基础。

Objective:To investigate the mechanism of action of Xiebai powder,a famous traditional Chinese medicine(TCM)prescription,in the treatment of pediatric asthmatic bronchitis based on network pharmacology.Methods:TCMSP database was used to obtain the effective constituents of Xiebai powder and their action proteins-gene targets,and databases including GeneCards and Drug Bank were used to obtain the main disease targets.STRING data platform was used to perform the protein-protein interaction network analysis,and Metascape data platform was used to perform gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Cytoscape 3.8.0 was used to construct a“TCM drug-common target-main pathway”network.Results:The above analysis obtained the main active components of Xiebai powder in the treatment of pediatric asthmatic bronchitis,including kaempferol,quercetin,licochalcone A,naringenin,and 18α-hydroxyglycyrrhizin,and their core targets included MAPK1,MAPK3,IKBKB,IL-6,TNF,MAPK8,CASP3,and MAPK14.Molecular docking showed a good binding effect between most targets had compounds.The targets were mainly enriched in a variety of inflammatory pathways,such as the IL-17 signaling pathway,the TNF signaling pathway,and the HIF-1 signaling pathway.Conclusion:Xiebai powder can reduce cytokine storm and alleviate airway spasm in asthmatic bronchitis through the interaction between multiple targets and pathways.This study provides a theoretical basis for Xiebai powder in the treatment of pediatric asthmatic bronchitis.