基于网络药理学探讨小儿止哮平喘颗粒治疗支气管哮喘的作用机制

Study on the mechanism of Xiaoer Zhixiao Pingchuan Granule(小儿止哮平喘颗粒)in the treatment of bronchial asthma based on network pharmacology

目的运用网络药理学探讨小儿止哮平喘颗粒治疗支气管哮喘的作用机制。方法通过TCMSP和SymMap数据库筛选小儿止哮平喘颗粒的活性成分及其作用靶点,通过NCBI Gene、GeneCards、TTD、KEGG、MalaCards、PharmGKB、OMIM等数据库筛选支气管哮喘的疾病相关靶点,获取活性成分作用靶点与疾病相关靶点的交集靶点(共同靶点),即小儿止哮平喘颗粒治疗支气管哮喘的潜在作用靶点。运用Cytoscape3.2.1软件构建“中药-成分-靶点-疾病”网络,将上述共同靶点导入String数据库,获取数据后在Cytoscape3.2.1软件中构建“成分靶点-疾病靶点”(T-D)网络,利用Metascape数据库进行GO和KEGG通路富集分析。结果共筛选得到289个活性成分及470个潜在作用靶点;获得豆甾-4-烯-3-酮、白矢车菊素、丹参醌酚I、飞燕草素、(E)-(4-甲基亚苄基)-(4-苯基三唑-1-基)胺、油酸等核心活性成分;RAC-α丝氨酸/苏氨酸蛋白激酶(RAC-alpha serine/threonine-protein kinase,AKT1)、p53蛋白(cellular tumor antigen p53,TP53)、黏着连接蛋白β1(cateninβ1,CTNNβ1)、转录因子激活蛋白-1(transcription factor AP-1,JUN)、Harvery鼠肉瘤病毒癌基因(GTPase HRas,HRAS)、生长因子受体结合蛋白2(growth factor receptor-bound protein 2,GRB2)、过氧化物酶体增殖激活受体γ(peroxisome proliferator-activated receptor gamma,PPARG)等核心靶点;筛选得到AGE-RAGE信号通路、钙信号通路、cAMP信号通路、TNF信号通路、PI3K-Akt信号通路等关键信号通路。结论小儿止哮平喘颗粒可通过多成分、多靶点调控多种通路达到治疗小儿支气管哮喘的作用,为其分子机制研究奠定了一定的基础。

Objective To explore the mechanism of Xiaoer Zhixiao Pingchuan Granule(小儿止哮平喘颗粒)in the treatment of bronchial asthma by means of network pharmacology.Methods The active components and action targets of Xiaoer Zhixiao Pingchuan Granule were screened by TCMSP and SymMap database,and the diseaserelated targets of bronchial asthma were screened by NCBIGene,GeneCards,TTD,KEGG,MalaCards,PharmGKB,OMIM and other databases,and the intersection targets(common targets)of active components and disease-related targets were obtained,that is,the potential targets of Xiaoer Zhixiao Pingchuan Granule in the treatment of bronchial asthma.The"traditional Chinese medicine-chemical composition target-disease"network was constructed by Cytoscape3.2.1 software,and the above common targets were imported into String database to obtain data.The"component target-disease target"network was constructed in Cytoscape3.2.1 sofiware,and CO and KEGG pathway enrichment analysis was carried out by using Metascape database.Results A total of 289 active components and 470 potential targets were screened,and the core active components such as ethycholest-4-en-3-one,(+)-Leucocyanidin,miltionone I,delphinin,(E)-(4-methylbenzylidene-(4-phenyltriazol-1-yl)amine,oleic acid),AKT1,TP53,CTNNβ1,JUN,HRAS,GRB2 and PPARG were obtained.ACE-RACE signal pathway,calcium signal pathway,cAMP signal pathway,TNF signal pathway,PI3K-Akt signal pathway and other key signal pathways were screened.Conclusion Xiaoer Zhixiao Pingchuan Granule can treat bronchial asthma by regulating multiple pathways with multi-components and multi-targets,which lays a foundation for the study of its molecular mechanism.