基于UPLC-Q-TOF-MS/MS及网络药理学探讨麻杏止哮颗粒治疗哮喘的有效成分和作用机制

目的 基于UPLC-Q-TOF-MS/MS技术和网络药理学探讨麻杏止哮颗粒治疗哮喘的有效成分和作用机制。方法 通过UPLC-Q-TOF-MS/MS技术及中药系统药理学数据库与分析平台（TCMSP）数据库筛选麻杏止哮颗粒的活性成分和相关靶点；利用Disgenet、Genecards数据库检索哮喘疾病靶点，利用韦恩图绘制平台获取共有靶点，并将信息导入Cytoscope3.9.1软件和STRING在线分析平台，进行网络拓扑学分析，构建药物关键活性成分-关键靶点网络和药物-有效成分-核心靶点网络；基于核心靶点通过DAVID数据库进行基因本体（gene ontology，GO）和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）富集分析。结果 结合质谱分析与数据库筛选得到药物活性成分24个，药物靶点147个，疾病靶点1483个，共同靶点106个，关键活性成分23个；经蛋白质相互作用分析及网络拓扑分析后，获取核心靶点10个，分别是肿瘤坏死因子、白细胞介素-6、细胞肿瘤抗原p53、白细胞介素-1β、血管内皮生长因子A、表皮生长因子受体、分裂原活化蛋白激酶3、半胱氨酸蛋白酶3、基质金属蛋白酶9、纤连蛋白1，药物有效成分5个，包括槲皮素、异鼠李素、汉黄芩素、柚皮素、儿茶素；GO富集到基因功能69个，KEGG富集到基因通路70条，分析结果表明，麻杏止哮颗粒治疗哮喘的作用机制是通过调节晚期糖基化终末化产物-晚期糖基化终末产物受体信号通路在糖尿病并发症中的作用、分裂原活化蛋白激酶信号通路、白细胞介素-17信号通路、磷脂酰肌醇3激酶-蛋白激酶B信号通路、人类巨细胞病毒感染通路等来发挥治疗哮喘的作用。结论 初步揭示了麻杏止哮颗粒治疗哮喘的有效成分和作用机制，为麻杏止哮颗粒药效物质基础研究奠定基础，为质量控制提供参考依据。

Exploring effective components and mechanism of action of Maxing Zhixiao Granules in treatment of asthma based on UPLC-Q-TOF-MS/MS and network pharmacology

Objective To explore the effective components and mechanism of acion of Maxing Zhixiao Granules in the treatment of asthma based on UPLC-Q-TOF-MS/MS technology and network pharmacology. Methods The active components and related targets of Maxing Zhixiao Granules were screened by UPLC-Q-TOF-MS/MS technology and the database of Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP); The targets of asthma diseases were searched using Disgenet and Genecards databases, and the Venn diagram drawing platform was used to obtain common targets. The information was imported into Cytoscope 3.9.1 software and STRING online analysis platform for network topology analysis to construct drug key active ingredient-key target network diagram and drug-active ingredient-core target network; Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) were enriched and analyzed by DAVID database based on core targets. Results Combined with mass spectrometry analysis and database screening, 24 active pharmaceutical ingredients, 147 drug targets, 1483 disease targets, and 106 common targets and 23 key active ingredients were obtained. After protein interaction analysis and network topology analysis, 10 core targets were obtained, including tumor necrosis factor, interleukin-6, cellular tumor antigen p53, interleukin-1 beta, vascular endothelial growth factor A, epidermal growth factor receptor, mitogen-activated protein kinase 3, caspase-3, matrix metalloproteinase-9, fibronectin, five active ingredients, including quercetin, isorhamnetin, wogonin, naringenin, catechin; GO was enriched to 69 gene functions, and KEGG was enriched to 70 gene pathways. The analysis results showed that the mechanism of action of Maxing Zhixiao Granules in the treatment of asthma is to regulate the role of advanced glycation end products-advanced glycation end products receptor signaling pathway in diabetic complications, mitogen-activated protein kinase signaling pathway, interleukin-17 signaling pathway, phosphatidylinositol 3 kinase-protein kinase B signaling pathway, and human cytomegalovirus infection pathway, etc. Conclusion This study preliminarily revealed the effective components and mechanism of action of Maxing Zhixiao Granules in the treatment of asthma, laying a foundation for the basic research on the pharmacodynamic substances of Maxing Zhixiao Granules and providing a reference for quality control.