基于网络药理学探讨麻杏二三汤治疗支气管哮喘作用机制

Discussion on Mechanism of Maxing Ersan Tang in Treating Bronchial Asthma Based on Network Pharmacology

目的:联合网络药理学数据库研究麻杏二三汤治疗支气管哮喘的作用机制。方法:运用传统中药系统药理学数据库和分析平台与有机小分子生物活性数据库获取麻黄、苦杏仁、陈皮、半夏、茯苓、紫苏子、莱菔子、白芥子、诃子、甘草的有效成分及对应靶点;从人类基因数据库和在线人类孟德尔遗传数据库获取支气管哮喘相关靶标,同时利用Venny 2.1在线网络获取交集基因;运用Cytoscape(Version3.7.2)和STRING数据库构建药物-成分-靶标-疾病网络图和蛋白质-蛋白质相互作用网络,进而运用cytoHubba插件鉴定出核心靶标。最后,运用Metascape数据库进行基因本体(GO)富集分析与京都基因和基因组百科全书(KEGG)通路富集分析。结果:研究筛选得到麻杏二三汤治疗支气管哮喘的主要治疗靶标包括血管内皮生长因子A(VEGFA)、白细胞介素-6(IL-6)、肿瘤坏死因子(TNF)、禽肉瘤病毒17(JUN)、p53肿瘤蛋白(TP53)、信号转导及转录激活蛋白3(STAT3)、促分裂素原活化蛋白激酶3(MAPK3)、前列腺内过氧化物合成酶2(PTGS2)、促分裂素原活化蛋白激酶1(MAPK1)、半胱氨酸-天冬氨酸蛋白酶3(CASP3)等,涉及磷酯酰肌醇-3-激酶-丝氨酸/苏氨酸激酶(PI3K-AKT)信号通路、白细胞介素-17(IL-17)信号通路、晚期糖基化终末产物-糖基化终末产物受体(AGE-RAGE)信号通路、TNF信号通路、肿瘤信号通路等。结论:麻杏二三汤通过多成分、多靶标、多通路共同发挥治疗支气管哮喘的作用。

Objective:To study the mechanism of Maxing Ersan tang in the treatment of bronchial asthma based on Network Pharmacology Database.Methods:The effective components and corresponding targets of Herba Ephedrae,Semen Armeniacae Amarum,Pericarpium Citri Reticulatae,Rhizoma Pinelliae,Poria,Fructus Perillae,Semen Raphani,Semen Sinapis,Fructus Chebulae and Radix et Rhizoma Glycyrrhizae were obtained from the Chinese Medicine System Pharmacology Database and Analysis Platform as well as PubChem Database.Bronchial asthma-related targets were obtained from Human Gene Database and Online Mendelian Inheritance In Man,and intersection genes were obtained by Venny 2.1 Online Network.Cytoscape(Version3.7.2)and STRING Database were used to construct network of drug-active component-target-disease and protein-protein interaction network,and then the plug-in of CytoHubba was used to identify core targets.Lastly,Metascape Database was used to analyze Gene Ontology(GO)enrichment analysis and kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.Results:The main therapeutic targets of Maxing Ersan tang in treating bronchial asthma included vascular endothelial growth factor A(VEGFA),interleukin-6(IL-6),tumor necrosis factor(TNF),avian sarcoma virus 17(JUN),p53 tumor protein(TP53),signal transducer and activator of transcription 3(STAT3),mitogen-activated protein kinase 3(MAPK3),prostaglandin-endoperoxide synthase 2(PTGS2),mitogen-activated protein kinase 1(MAPK1)and Cysteine-aspartate protease-3(CASP3).The involved signaling pathways were phosphoinositol-3-kinase-serine/threonine kinase(PI3K-AKT)signaling pathway,interleukin-17(IL-17)signaling pathway,advanced glycation end product-receptor of AGE(AGE-RAGE)signaling pathway,tumor necrosis factor(TNF)signaling pathway,tumor signaling pathway,etc.Conclusion:Maxing Ersan tang plays a role in treating bronchial asthma through multiple components,multiple targets and multiple pathways.