基于网络药理学探讨麻黄治疗儿童哮喘作用机制

Mechanism of Mahuang in Treating Childhood Asthma Based on Network Pharmacology

目的:利用网络药理学相关资源研究麻黄治疗儿童哮喘的作用机制,以期为临床研发儿童哮喘药物提供新的思路和方向。方法:利用BATMAN-TCM数据库获取麻黄的活性成分及靶点,于人类基因组注释数据库Gene Cards检索儿童哮喘的靶标基因,筛选出两者共同的靶标基因,视为麻黄治疗儿童哮喘的潜在靶点,运用STRING平台构建这些潜在靶点蛋白之间相互作用的网络模型,使用DAVID数据库进行潜在靶点的GO分析和KEGG通路富集分析。结果:麻黄治疗儿童哮喘的活性成分共有104个活性成分,即麻黄素、麻黄碱、去甲基麻黄碱、毛果碱、伪麻黄碱、乙酸薄荷酯、亚油酸、芹菜素等,潜在作用靶点432个,主要涉及Ras signaling pathway、PI3KAkt[磷脂酰肌醇-3-激酶-蛋白激酶B信号通路,Phosphatidylinositol-3kinase(P13K)-protein Kinase B(AKT)]、MAPK(丝裂原活化蛋白激酶信号通路Mitogen-activated protein kinase)、Rap1 signaling pathway、TNF signaling pathway、HIF-1 signaling pathway 6条通路。结论:麻黄治疗儿童哮喘的作用机制可能是通过共同调节Ras、PI3KAkt、MAPK、Rap1、TNF、HIF-1等信号通路,作用于NFKB、IL-2、IL-4,IL-6、IL-9、IL-13、EGFR、AR、BCL2等相关受体,进而促进嗜酸性粒细胞、肥大细胞、中性粒细胞等多种细胞的凋亡,抑制炎症因子释放,降低血管壁通透性,减轻局部组织肿胀,从而进一步抑制炎症反应,避免气道重塑以及气流受限。

Objective:To explore the mechanism of Mahuang in the treatment of childhood asthma based on network pharmacology,so as to provide new ideas and directions for the clinical development of children’s asthma drugs.Methods:Using BATMAN-TCM to screen ingredients and potential targets of Mahuang,then retrieving target genes of childhood asthma from The Human Gene Database,to integrate both target genes,as a potential target of Mahuang treating childhood asthma,finally,to build these potential target protein interactions between network model by STRING platform,The GO classified enrichment analysis and the KEGG pathway enrichment analysis were performed by using DAVID database.Results:There are 104 active components of Mahuang in the treatment of childhood asthma,namely ephedrine,demethylephedrine,mangotine,pseudoephedrine,acetate peppermint ester,linoleic acid,apigenin,etc.,with 432 potential targets,which are mainly involved in the Ras signaling pathway,PI3 K-Akt,MAPK,Rap1 signaling pathway,TNF signaling pathway,HIF-1 signaling pathway.Conclusion:The mechanism of action of Mahuang treating childhood asthma may be through adjusting the Ras,PI3 K-Akt,MAPK,Rap1,TNF,signaling pathways,such as HIF-1 on NFKB,IL-2,IL-4,IL-6,IL-9,IL-13,EGFR,AR,and BCL2 receptors,to promote the eosinophils and mast cells,neutrophils and various cell apoptosis,inhibiting inflammatory cytokines release,reducing the permeability of blood vessel walls and local tissue swelling,so as to depress inflammation,avoid airway remodeling and limited airflow.