基于网络药理学探讨哮喘宁颗粒防治心理应激哮喘的作用网络与潜在机制

Exploration of the action network and potential mechanism of Xiaochuanning Granule in prevention and treatment of psychological stress asthma based on network pharmacology

目的运用网络药理学研究方法探讨哮喘宁颗粒防治心理应激哮喘的作用网络与潜在机制。方法在中药系统药理学分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)、中药分子机制的生物信息学分析网络(Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine,BATMAN-TCM)等数据平台筛选哮喘宁颗粒的主要有效成分与靶点;并通过相关疾病靶点数据库检索心理应激哮喘的相关靶点;通过韦恩图得到哮喘宁颗粒与心理应激哮喘之共同靶点,利用Cytoscape 3.7.2建立"药物-成分-靶点"作用网络,然后使用STRING数据库进行化合物-疾病共同靶点的蛋白互作分析(protein-protein interaction,PPI),运用Cytoscape 3.7.2的插件MCODE、cytohubba及拓扑运算后筛选关键靶点;利用David数据库进行基因本体(Gene Ontology, GO)分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)通路富集分析。结果筛选出哮喘宁颗粒39个主要有效成分和121个交集预测靶点,心理应激哮喘靶点1 063个;通过韦恩图得到共同靶点72个,继用cytohubba插件及拓扑运算得到重要基因,通过MCODE筛选出基因互作模块,从而得到MAPK1、MAPK8、TNF、VEGFA、EGF、PTGS2、JUN、IL-6等交集靶点;通过GO和KEGG富集分析得知这些靶点涉及信号转导、细胞增生正调控、MAPK信号通路激活等生物学过程,神经活性配体受体相互作用、TNF、NOD样受体、Toll样受体、钙离子、T细胞受体、PI3K-Akt等信号通路。结论哮喘宁颗粒可能通过多种有效成分作用于神经机制、免疫炎性反应、细胞增生等方面以综合调节"神经-内分泌-免疫"网络,从而防治心理应激哮喘。

Objective To explore the action network and potential mechanism of Xiaochuanning Granule in the treatment of psychological stress asthma by the means of network pharmacology.Methods We screened the main effective components and targets of Xiaochuanning Granule on the data platforms such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM)and studied the related targets of psychological stress asthma through the relevant disease target database.The common target of the drug and the disease was produced by Wayne diagram,and the drug-component-target interaction network was established by Cytoscape 3.7.2.Then the protein-protein interaction(PPI)network of common targets between compound and disease was analyzed with the STRING database.The key targets are screened by using plug-ins of Cytoscape 3.7.2 including MCODE,cytohubba and topology to screen.David database was used for Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results Totally 39 main active components,121 predicted intersection targets of Xiaochuanning Granule were screened out.Totally 1063 psychological stress asthma targets were screened out,72 common targets were achieved by Wayne diagram,crucial genes were calculated by cytohubba plug-in and topological operation,and gene interaction modules were screened out by MCODE.Therefore,the intersection Targets were obtained such as MAPK1,MAPK8,TNF,VEGFA,EGF,PTGS2,JUN,IL-6 and so on.GO and KEGG enrichment analysis suggested these targets were involved in biological processes such as signal transduction,positive regulation of cell proliferation,and activation of MAPK activity,etc.These common targets involve signaling pathways such as neuroactive ligand-receptor interaction,TNF,NOD-like receptor,Toll-like receptor,calcium signaling pathway,T cell receptor,PI3K-Akt and so on.Conclusion Xiaochuanning Granule may prevent and treat psychological stress asthma via the regulation of the“neuro-endocrine-immune network”through the nervous mechanism,immune inflammation,cell proliferation and other aspects.