基于网络药理学探讨紫苏子-葶苈子治疗支气管哮喘的作用机制

Discussion on Mechanism of Zisuzi(Perillae Fructus)-Tinglizi(Descurainiae Semen Lepidii Semen)Treating Bronchial Asthma Based on Internet Pharmacology

目的采用网络药理学方法筛选紫苏子-葶苈子药对治疗支气管哮喘(Asthma)的活性成分和作用靶点,明确治疗支气管哮喘的作用机制。方法利用中药系统药理学数据库与分析平台(TCMSP)预测紫苏子、葶苈子的有效成分及有效活性成分对应的靶点,运用Genecard数据库筛选的相关靶点,通过STRING11.0数据库构建蛋白-蛋白相互作用(protein-protein interaction,PPI)网络,利用Metascape数据库对“紫苏子-葶苈子有效活性成分-哮喘疾病靶点”进行GO注释分析和KEGG通路富集分析,通过Cytoscape软件建立“紫苏子-葶苈子-有效活性成分-靶点-通路”网络模型。结果筛选出紫苏子-葶苈子12个治疗哮喘的活性成分,包括槲皮素、木犀草素、山柰酚、β-谷甾醇、β-胡萝卜素等,潜在靶点184个,关键靶点31个,GO分析获得显著富集(P<0.05)的生物过程(BP)857条、细胞组分(CC)27条、分子功能(MF)52条,KEGG分析获得显著富集(P<0.05)通路131条。结论紫苏子-葶苈子的活性成分为槲皮素、木犀草素、山柰酚等,主要治疗靶点为JUN原癌基因(JUN)、胱天蛋白酶3(CASP3)、白介素-10(IL10)、白介素-6(IL6)、肿瘤坏死因子(TNF),治疗作用可能与影响多个生物进程(如对细胞因子的反应、对无机物的反应、细胞死亡的正向调节、细胞群增殖的负调控等)和多条代谢途径(如IL-17信号通路、晚期糖基化终产物及其受体AGE-RAGE信号通路等)有关。

Objective To screen the active components and targets of Zisuzi(Perillae Fructus)-Tinglizi(Descurainiae Semen Lepidii Semen)in the treatment of bronchial asthma by network pharmacology and clarify the mechanism of action in the treatment of bronchial asthma.Methods The traditional Chinese medicine system pharmacology database and analysis platform(TCMSP)was used to predict the active ingredients of Perilla frutescens and Tinglizia and their corresponding targets.The relevant targets were screened by the Genecard database,and the protein-protein-protein interaction(PPI)network was constructed by using STRING11.0 database.Metascape database was used to conduct GO annotation analysis and KEGG pathway enrichment analysis of"Zisuzi(Perillae Fructus)-Tinglizi(Descurainiae Semen Lepidii Semen)effective active ingredients-asthma disease targets".Cytoscape software was used to establish"Zisuzi(Perillae Fructus)-Tinglizi(Descurainiae Semen Lepidii Semen)-active ingredient-target-pathway"network model.Results A total of 12 active ingredients of Perilla-Tinglizi were screened for the treatment of asthma,including quercetin,luteolin,kaempferol,β-sitosterol,β-carotene,etc.There were 184 potential targets and key targets.A total of 31 points,857 biological process(BP),27 cellular components(CC)and 52 molecular function(MF)were significantly enriched(P<0.05)by GO analysis,and significantly enriched by KEGG analysis(P<0.05).Conclusion The active components of Perilla chinensis-Tinglizi are quercetin,luteolin,kaempferol,etc.The main therapeutic targets are JUN proto-oncogene(JUN),caspase 3(CASP3),interleukin-10(IL10),interleukin-6(IL6)and tumor necrosis factor(TNF).The therapeutic effects may be related to affecting multiple biological processes(such as response to cytokines,response to inorganic substances,positive regulation of cell death,proliferation of cell populations,negative regulation,etc.)and multiple metabolic pathways(such as IL-17 signaling pathway,advanced glycation end products and its receptor AGE-RAGE signaling pathway,etc.).