目的:基于网络药理学方法筛选固本平喘剂(补骨脂、地龙、防风)中的主要活性成分,探讨其治疗支气管哮喘的作用机制.方法:通过中药系统药理学数据库TCMSP数据库、中药与化学成分数据库,筛选固本平喘剂的活性成分及靶标.利用Genecards、OMIM数据库获得支气管哮喘的潜在靶标基因.将两者靶基因进行映射后通过Cytoscape3.6.1软件构建"成分-靶标"网络、结合String数据库构建蛋白质相互作用网络扩充核心靶点.依托功能注释生物信息学分析平台DAVID数据库对固本平喘剂的作用靶点进行基因本体(gene ontology,GO)生物学过程和基因组百科全书(kyoto encyclopedia of genes and ge-nomes,KEGG)通路富集注释分析,通过Autodock vina软件进行分子对接以验证结果.结果:符合筛选条件的共有53个活性成分,补骨脂18个,地龙17个,防风18个,筛选得到固本平喘剂关键成分,包括补骨脂黄酮类、补骨脂查耳酮类、汉黄芩素、补骨脂酚、β-谷甾醇等;通过GenCards、OMIM数据库剔除重复后,共收集支气管哮喘潜在靶点2 358个.将固本平喘剂和支气管哮喘靶点进行映射取交集共得到237个交叉靶点,即固本平喘剂治疗支气管哮喘潜在作用靶点.以degree值大于二倍均值的靶点为 PTGS2、ESR1、ACHE、ESR2、PTGS1、DPP4、ADORA3,degree 值排名前 5 的靶蛋白为 PIK3CA、MAPK3、MAPK1、TP53、AKT1.主要涉及PI3K-Akt信号通路、TNF信号通路、趋化因子信号通路、FoxO信号通路、MAPK信号通路、Toll样受体信号通路、T细胞受体信号通路等.结论:固本平喘剂治疗支气管哮喘潜在作用靶点有PTGS2、ESR1、ACHE、ESR2、PTGS1、DPP4、ADORA3、PIK3CA、MAPK3、MAPK1、TP53、AKT1,可能通过抗感染、调节免疫、抑制气道重塑等发挥作用.
Study on the Mechanism of Action of Essence-Consolidating Antiasthmatic Agent in the Treatment of Bronchial Asthma Based on Network Pharmacology
Objective:To screen the main active ingredients and targets of Essence-Consolidating Anti-asthmatic Agent such as Buguzhi(Fructus Psoraleae),Dilong(Pheretima),and Fangfeng(Radix Saposhnikoviae)based on network pharmacology method,and to explore its mechanism of action in the treatment of bronchial asthma.Methods:The active ingredients and targets of Essence-Consolidating Anti-asthmatic Agent were screened through TCMSP database,TCM and chemical composition database.Genecards and OMIM database were used to obtain the potential target genes of bronchial asthma.After mapping the two target genes,the"ingredient-target"network was constructed by Cytoscape3.6.1 software,and the protein-protein interaction network was constructed by combining String database to ex-pand the core targets.The targets of Essence-Consolidating Anti-asthmatic Agent were enriched by gene ontology(GO)biological process and Kyoto encyclopedia of genes and genomes(KEGG)pathway annotation analysis based on the functional annotation bioinfor-matics analysis platform DAVID database,and the results were verified by molecular docking with Autodock vina software.Results:A to-tal of 53 active ingredients were screened,including 18 Buguzhi,Dilong,and 18 Fangfeng,and the key ingredients of Essence-Consolida-ting Anti-asthmatic Agent were screened,including Psoraleae flavonoids,Psoraleae chalcone,hanbaiqin,Psoraleae phenol,β-sitosterol,etc.After removing duplicates from GenCards and OMIM databases,a total of 2,358 potential targets for bronchial asthma were collect-ed.After mapping Essence-Consolidating Anti-asthmatic Agent and bronchial asthma targets,237 cross targets were obtained,which were the potential targets of Essence-Consolidating Anti-asthmatic Agent for the treatment of bronchial asthma.The targets with degree value greater than twice the mean were PTGS2,ESR1,ACHE,ESR2,PTGS1,DPP4,and ADORA3,and the top five target proteins with degree value were PIK3CA,MAPK3,MAPK1,TP53,and AKT1.The main involved signaling pathways were PI3K-Akt signaling path-way,TNF signaling pathway,chemokine signaling pathway,FoxO signaling pathway,MAPK signaling pathway,Toll-like receptor signa-ling pathway,T cell receptor signaling pathway,etc.Conclusion:The potential targets of Essence-Consolidating Anti-asthmatic Agent in the treatment of bronchial asthma are PTGS2,ESR1,ACHE,ESR2,PTGS1,DPP4,ADORA3,PIK3CA,MAPK3,MAPK1,TP53,AKT1,which may play a role by anti-infection,regulating immunity,inhibiting airway remodeling and so on.
Essence-Consolidating Anti-asthmatic Agentbronchial asthmanetwork pharmacologymolecular dockingmechanism of ac-tion
万方数据
维普
