天然产物研究与开发 ›› 2025, Vol. 37 ›› Issue (4): 707-722.doi: 10.16333/j.1001-6880.2025.4.013 cstr: 32307.14.1001-6880.2025.4.013

• 开发研究 • 上一篇    下一篇

基于UPLC-Q-TOF-MS和网络药理学探究玉叶解毒颗粒治疗上呼吸道感染作用机制

冯小龙1,李鹏辉1,龙红萍2,陈  俊3,陈开义3,姜金生3,蔡  媛1*,彭艳梅 1*   

  1. 1湖南省中医药研究院,长沙 4100132湖南中医药大学第一附属医院,长沙 4100073三金集团湖南三金制药有限责任公司,常德 415000

  • 出版日期:2025-04-30 发布日期:2025-04-27
  • 基金资助:
    湖南省重点研发计划(2022SK2046);芙蓉实验室科技攻关项目(2023SK2097);湖南省自然科学基金(2025JJ80175);广西重点研发计划(桂科AB22035054)

Study on the mechanism of Yuye Detoxification Particle in the treatment of upper respiratory infection based on UPLC-Q-TOF-MS and network pharmacology

FENG Xiao-long1,LI Peng-hui1,LONG Hong-ping2,CHEN Jun3,CHEN Kai-yi3,JIANG Jin-sheng3,CAI Yuan1*,PENG Yan-mei1*   

  1. 1Hunan Academy of Traditional Chinese Medicine,Changsha 410013,China; 2The First Hospital of Hunan University of Chinese Medicine,Changsha 410007,China; 3Sanjin Group Hunan Sanjin Pharmaceutical Co.Ltd.,Changde 415000,China

  • Online:2025-04-30 Published:2025-04-27

摘要:

本研究旨在采用超高效液相色谱-四级杆-飞行时间质谱(ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometryUPLC-Q-TOF-MS)技术解析玉叶解毒颗粒灌胃给药大鼠后的入血成分,研究其体内主要的代谢过程;并结合网络药理学和体外实验分析验证其入血成分治疗上呼吸道感染(upper respiratory infectionURI)的潜在作用机制。对SD大鼠连续灌胃给药7天后收集血清样本,并采用UPLC-Q-TOF-MS技术在正、负离子模式下对血清样本进行数据采集,结合前期体外化学成分质谱数据以及提取各化学成分的精确质荷比等信息对玉叶解毒颗粒在大鼠体内的入血原型成分和代谢产物进行辨识研究;通过网络药理学分析探究入血成分治疗URI的潜在机制,并建立可视化网络图,筛选活性成分,并验证其体外抗炎作用。研究结果表明,在大鼠体内共检测到21个原型成分和23个代谢产物。经网络药理学分析,入血原型成分与URI疾病存在74个交集靶点,GO功能富集分析得到441种生物过程、57种细胞组分、79种分子功能;KEGG通路富集分析得到30条干预URI相关通路,由此预测玉叶解毒颗粒主要通过炎症、调节免疫、抗病毒、抗肺损伤等途径治疗URI。蛋白互作网络分析得到白细胞介素6、肿瘤坏死因子、蛋白激酶Bα13个核心靶点;分子对接进一步验证了木犀草素、金合欢素、绿原酸、山栀苷甲酯、玉叶金花苷酸甲酯5个化学成分与13个核心靶点具有良好的结合能力;体外实验结果显示筛选出的5个活性成分均具有显著抗炎活性且呈现明显的浓度梯度依赖性。综上,该研究为玉叶解毒颗粒化学物质组研究奠定了基础,初步揭示了其治疗URI的复杂调控机制,为下一步深入研究作用机制提供了理论依据。

关键词: 玉叶解毒颗粒, UPLC-Q-TOF-MS, 入血成分, 代谢产物, 网络药理学, 上呼吸道感染

Abstract:

In this study,ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) technology was employed to analyze the blood components of rats after intragastric administration of Yuye Detoxification Particle and investigate their main metabolic processes in vivo.Additionally,network pharmacology and in vitro experiments were combined to analyze and verify the potential mechanism of the blood components in the treatment of upper respiratory infection (URI).Following consecutive 7-day intragastric administration of the test substance to SD rats,serum samples were collected.UPLC-Q-TOF-MS was then utilized to conduct data acquisition on these serum samples in both positive and negative ion modes.Combined with the previous in vitro chemical composition mass spectrometry data and the extraction of the accurate mass-to-charge ratio and other information of each chemical composition,the prototype components and metabolites of Yuye Detoxification Particle in rats were identified.Through network pharmacology analysis,the potential mechanism of blood components in treating URI was analyzed,and a visualized network diagram was established to screen active ingredients and verify the anti-inflammatory effects in vitro.As a result,a total of 21 prototype components and 23 metabolites were detected in rats.Network pharmacology analysis revealed that 74 overlapping targets exist between the blood-absorbed prototype components and those related to URI disease.GO enrichment analysis yielded 441 biological processes,57 cellular components,and 79 molecular functions.KEGG enrichment analysis obtained 30 intervention pathways related to URI.It is predicted that Yuye Detoxification Particle mainly treat URI through pathways such as inflammation,immune regulation,antiviral,and anti-lung injury.Protein-protein interaction analysis obtained 13 core targets such as interleukin-6,tumor necrosis factor,and protein kinase Bα.Molecular docking further verified that five chemical components,namely luteolin,acacetin,chlorogenic acid,shanzhiside methyl ester,and mussaenoside acid methyl ester,have good binding ability with 13 core targets.In vitro experiment results showed that the five selected active ingredients all had significant anti-inflammatory activity and showed an obvious concentration gradient dependence.In conclusion,this study laid a foundation for the research on the chemical substance group of Yuye Detoxification Particle,initially revealed the complex regulatory mechanism of its treatment to URI,and provided a theoretical basis for further in-depth research on the mechanism of action.

Key words: Yuye Detoxification Particle, UPLC-Q-TOF-MS, blood component, metabolites, network pharmacology, upper respiratory infection

中图分类号:  R285.5