基于UPLC-Q-TOF-MS/MS联合网络药理学及分子对接研究五味清浊颗粒治疗腹泻药效物质基础和作用机制  

Pharmacodynamic substance basis and mechanism of Wuwei Qingzhuo granules for diarrhea based on combination of UPLC-Q-TOF-MS/MS with network pharmacology and molecular docking

作　　者：李伟[1] 孙佳 李思雨 余秋香 王添敏[1] 宋慧鹏 张慧[1] LI Wei;SUN Jia;LI Si-yu;YU Qiu-xiang;WANG Tian-min;SONG Hui-peng;ZHANG Hui(College of Pharmacy,Liaoning University of Traditional Chinese Medicine,Dalian Liaoning 116600)

机构地区：[1]辽宁中医药大学药学院,辽宁大连116600

出　　处：《中南药学》2024年第2期423-432,共10页Central South Pharmacy

基　　金：蒙药传统汤散剂剂型改良研究与示范项目(No.2021SZD0030)。

摘　　要：目的基于UPLC-Q-TOF-MS/MS技术鉴定五味清浊颗粒中的化学成分,联合网络药理学、分子对接技术探讨其治疗腹泻药效物质基础和作用机制。方法采用Eclipsepius C18色谱柱(50 mm×2.1 mm,1.8μm),以0.1%甲酸水溶液(A)-乙腈(B)为流动相进行梯度洗脱,柱温为30℃,流速为0.4 mL·min^(-1)。质谱采用电喷雾离子源(ESI)正、负离子模式,扫描范围m/z 50~2000条件下采集多级质谱碎片信息。应用网络药理学构建“核心成分-作用靶点-通路”的网络,对其潜在药效物质基础进行预测。利用AutoDock Vina进行分子对接验证。结果共鉴定出86个主要化学成分,包括生物碱类25个、黄酮类23个、有机酸类12个、鞣质类16个、苯丙素类2个、其他类化合物8个。网络药理学分析结果显示,槲皮素、木犀草素、鞣花酸、胡椒碱、山柰酚、荜茇宁主要作用于IL-6、TNF、EGFR、IFNG、IL-10、IL-8等核心靶点,调节PI3K-Akt、HIF-1、JAK-STAT等关键信号通路来发挥治疗腹泻作用。分子对接结果显示核心成分与核心靶点间具有良好的结合性能。结论该研究成功采用UPLC-Q-TOF-MS/MS技术对五味清浊颗粒化学成分进行全面分析鉴定,初步阐明其治疗腹泻的作用机制,为其药效物质基础和质量控制奠定基础。Objective To identify the chemical components of Wuwei Qingzhuo granules by UPLC-Q-TOF-MS/MS technology,and to deteremine their pharmacodynamic substance basis and mechanism in the treatment of diarrhea by combining network pharmacology and molecular docking.Methods Eclipsepius C18 column(50 mm×2.1 mm,1.8μm)was used,with 0.1%formic acid in water(A)-acetonitrile(B)as the mobile phase was 0.4 mL·min^(-1)at 30℃.Mass spectrometry used electrospray ion source(ESI)positive and negative ion modes to collect multi-level mass spectrometry fragment information in the scanning range of m/z 50~2000.Network pharmacology was used to establish a network of“core components-targets-pathways”to predict the material basis of its potential pharmacodynamics.AutoDock Vina was used to validate molecular docking.Results Totally 86 main chemical components were identified,including 25 alkaloids,23 flavonoids,12 organic acids,16 tannins,2 phenylpropanoids and 8 other compounds.The network pharmacological analysis showed that quercetin,luteolin,ellagic acid,piperine,kaempferol,and piperlonguminine mainly acted on such core targets as interleukin-6(IL-6),tumor necrosis factor(TNF),epidermal growth factor receptor(EGFR),interferonγ(IFNG),interleukin-10(IL-10),and interleukin-8(IL-8),and regulated PI3K-Akt,HIF-1,JAK-STAT and other key signaling pathways in the treatment of diarrhea.The molecular docking showed that the core components had good binding properties with the core targets.Conclusion In this study,UPLC-Q-TOF-MS/MS technology has been successfully used to comprehensively analyze and identify the chemical compositions in Wuwei Qingzhuo granules,which preliminarily elucidates the mechanism of action for diarrhea,and lays a foundation for the pharmacodynamic substance basis and quality control.

关 键 词：五味清浊颗粒 UPLC-Q-TOF-MS/MS 网络药理学 分子对接 化学成分 

分 类 号：R285.5[医药卫生—中药学]