基于网络药理学预测桔梗治疗支气管哮喘的作用机制  

Predicting the mechanism of platycodon grandiflorum in treatment of bronchial asthma based on net⁃work pharmacology

作　　者：莫蕊辰 王娓娓 赵磊[1] 牟林茂[2] MO Ruichen;WANG Weiwei;ZHAO Lei;MU Linmao(Shandong University of Traditional Chinese Medicine,Jinan 250000,China)

机构地区：[1]山东中医药大学,济南250000 [2]山东省立医院

出　　处：《山东医药》2021年第5期13-17,共5页Shandong Medical Journal

摘　　要：目的运用网络药理学分析桔梗有效成分、支气管哮喘靶点,并预测桔梗治疗支气管哮喘的作用机制。方法通过TCMSP数据库获取桔梗的有效成分,通过Pubchem、Swiss target prediction数据库收集桔梗的成分作用靶点,将靶点导入Cytoscape3.6.2软件,制作有效成分与相关作用靶点的关系网络图,得到桔梗中发挥相对重要作用的成分及靶点。通过TTD、Drugbank、DisGeNET、CTD、genecards、OMIM、GAD、KEGG数据库获取支气管哮喘靶点,利用Uniport数据库进行蛋白—基因名标准化。将桔梗靶点与支气管哮喘靶点取交集、去重复,得到桔梗治疗支气管哮喘的预测靶点。将预测靶点导入STRING数据库得到桔梗治疗支气管哮喘靶点的PPI网络,通过Cyto⁃scape3.6.2软件对PPI网络进行可视化处理。利用Cytoscape3.6.2软件中的Network Analyzer、cytoHubba插件对PPI网络进行核心靶点拓扑,得到桔梗治疗支气管哮喘的核心靶点,利用DAVID数据库对核心靶点进行GO功能富集分析及KEGG通路分析。结果共获得符合筛选条件的桔梗有效成分22种(包括刺槐素、木犀草素、桔梗皂苷元等),桔梗成分靶点311个、支气管哮喘靶点1551个。共获得桔梗治疗支气管哮喘的有效靶点137个,其中核心靶点10个,包括半胱氨酸蛋白酶3(CASP3)、分裂原活化蛋白激酶3(MAPK3)、表皮生长因子受体(EGFR)、基质金属蛋白酶9(MMP9)等。GO功能富集分析共得到GO条目77个,其中生物过程53个、分子功能13个、细胞组成11个,涉及一氧化氮生物合成过程的正调控、蛋白磷酸化正调控、平滑肌细胞增殖的阳性调节等;KEGG通路分析共得到KEGG通路35条,涉及ErbB信号通路、mTOR信号通路、HIF-1信号通路、VEGF信号通路、PI3K-Akt信号通路等。结论桔梗中的多种有效成分如刺槐素、木犀草素可能通过CASP3、MAPK3、EGFR等靶点,对ErbB、mTOR、HIF-1、VEGF、PI3K-Akt、MAPK等信号通路进行调控,整体协同�Objective To analyze the active ingredients and the targets of platycodon grandiflorum in the treatment of bronchial asthma based on network pharmacology,and to predict its mechanism of action.Methods The active ingre⁃dients of platycodon grandiflorum were obtained from TCMSP database,the target action points of platycodon platycodon were obtained from Pubchem and Swiss Target prediction databases,and the targets were imported into Cytoscape 3.6.2 software;the relational network diagram of the active ingredients and relevant targets were made to obtain the components and targets that played relatively important roles in platycodon grandiflorum.The targets of bronchial asthma were obtained from Threapeutic Target Database(TTD),Drugbank,DisGeNET,Comparative Toxicogenomics Database(CTD),Gene⁃cards,Online Mendelian Inheritance in Man(OMIM),Genetic Association Database(GAD),and the databases of Kyoto Encyclopedia of Genes and Genomes(KEGG),and meanwhile,standardization of protein-gene names was carried out by using Uniport database.We took the intersection of the platycodon grandiflorum targets and the bronchial asthma targets,and removed the repeated ones to obtain the predicted targets of platycodon grandiflorum in the treatment of bronchial asthma.The predicted targets were imported into the String database to obtain the protein-protein interactions(PPI)network of platycodon grandiflorum in the treatment of bronchial asthma,and the PPI network was visualized by Cytoscape 3.6.2 soft⁃ware.The Network Analyzer and cytoHubba plug-ins in the Cytoscape3.6.2 software were used to carry out the core target topology of PPI network,and the core targets in the treatment of bronchial asthma were obtained.DAVID database were used to carry out GO function enrichment analysis and KEGG pathway analysis on the core targets.Results A total of 22 effective ingredients of platycodon grandiflorum(including acacetin,luteolin,platycodigenin,etc.),311 targets of platy⁃codon grandiflorum and 1551 targets of bronchial asthma were ob

关 键 词：网络药理学 桔梗 支气管哮喘 作用机制 核心靶点 

分 类 号：R285[医药卫生—中药学]