基于UPLC-Q-Exactive-Orbitrap-MS和网络药理学的紫贝颗粒治疗感染后咳嗽的药效物质基础及作用机制

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中文摘要：目的基于UPLC-Q-Exactive-Orbitrap-MS技术鉴定紫贝颗粒(ZBG)水提物中化学成分，并结合网络药理学和分子对接方法分析ZBG治疗感染后咳嗽(PIC)的药效物质基础及作用机制。方法采用UPLC-Q-Exactive-Orbitrap-MS技术，表征ZBG的化学成分，并导入中药系统药理学数据库与分析平台(TCMSP)、PharmMapper数据库检索药物成分靶点;利用GeneCards、OMIM数据库收集PIC相关疾病靶点，取交集后利用STRING数据库、Cytoscape软件构建"ZBG成分-共有靶点"蛋白质-蛋白质相互作用(PPI)网络并筛选核心成分与核心靶点。利用DAVID数据库对共同靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析，借助分子对接预测核心成分和关键靶点的结合能力。结果通过质谱分析鉴定得到ZBG水提物化学成分109个，结合数据库筛选得到ZBG治疗PIC的潜在活性成分90个，与PIC治疗相关的作用靶点122个。其中，芦丁、柚皮苷、黄芩苷、异绿原酸A、香叶木苷、甘草酸等14个成分为ZBG治疗PIC的核心成分，表皮生长因子受体(EGFR)、非受体酪氨酸蛋白激酶(SRC)、丝氨酸和苏氨酸激酶1(AKT1)、磷脂酰肌醇3-激酶调控亚基(PIK3R1)、丝裂原活化蛋白激酶(MAPK8)、基质金属蛋白酶-9(MMP-9)等6个靶点为ZBG治疗PIC的关键靶点。结合KEGG富集结果表明，ZBG治疗PIC的机制与EGFR信号通路、MAPK信号通路和PI3K-Akt信号通路有关。分子对接结果表明ZBG中14个核心成分与6个关键靶点均有较好的结合活性，其结合模式主要以氢键为主。结论 ZBG可通过多成分、多靶点、多通路治疗PIC，为后续深入揭示其药效物质基础及作用机制提供了参考。

外文标题：Study on pharmacodynamic substances and mechanism of Zibei Granules in treatment of postinfectious cough based on UPLC-Q-Exactive-Orbitrap-MS and network pharmacology

外文摘要：Objective To identify the chemical constituents in Zibei Granules(ZBG)by ultrahigh performance liquid chromatography-electrostatic field Orbitrap MS(UPLC-Q-Exactive-Orbitrap-MS),and to analyze the pharmacological basis of its efficacy in the treatment of postinfectious cough(PIC)and its mechanism of action by combining with network pharmacology and molecular docking.Methods UPLC-Q-Exactive-Orbitrap-MS was used to characterize the chemical constituents of ZBG.TCMSP and PharmMapper databases were used to screen the active components and related targets.The targets of PIC were searched using GeneCards and OMIM databases.The intersection of the main components of ZBG and the targets related to PIC was taken,and the"ZBG components-common targets"network and protein-protein interaction network were constructed by STRING database and Cytoscope software to screen for core components and core targets.Gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichent analysis were performed by DAVID database.Finally,the binding ability of core components and potential key targets were predicted by molecular docking.Results A total of 109 ingredients were identified from the water extract of ZBG by UPLC-Q-Exactive-Orbitrap-MS.90 potential active ingredients and 122 targets of ZBG for the treatment of PIC were screened out through network pharmacology analysis,of which 14 core components include rutin,naringin,baicalin and so on.The six key targets of PIC involved EGFR,SRC,AKT1,PIK3R1,MAPK8,MMP-9.The KEGG enrichment results indicated that the key mechanism of ZBG against PIC may through the synergistic regulation of EGFR,MAPK and PI3K-Akt signaling pathway.Molecular docking results showed that the core components have a good affinity with the key targets,and their binding modes were mainly based on hydrogen bonding.Conclusion ZBG has the characteristics of multi-components,multi-targets and multi-pathways effects on the treatment of PIC.It would provide a scientific foundation for the further research on active components and mechanisms of ZBG in treating PIC.

外文关键词：

Zibei Granulespostinfectious coughUPLC-Q-Exactive-Orbitrap-MSnetwork pharmacologymolecular dockingrutinnaringinbaicalinisochlorogenic acid Adiosminglycyrrhizic acid

作者：

张紫岚、王停、亢倩丽、邓方圆、林红梅

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作者单位：

北京中医药大学生命科学学院,北京 100029

国家中医药管理局名医名方重点研究室,北京 100029

北京中医药大学北京中医药研究院中药新药研发中心,北京 100029

国家药品监督管理局中医药研究与评价重点实验室,北京 100029

北京中医药大学中药学院,北京 100029

北京中医药大学北京中医药研究院,北京 100029

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关键词：

紫贝颗粒感染后咳嗽 UPLC-Q-Exactive-Orbitrap-MS 网络药理学分子对接芦丁柚皮苷黄芩苷异绿原酸A 香叶木苷甘草酸

出版年：

2024

DOI：

10.7501/j.issn.1674-6376.2024.12.004

药物评价研究

天津药物研究院中国药学会

药物评价研究

CSTPCD北大核心

影响因子：1.199

ISSN：1674-6376

年,卷(期)：2024.47(12)