天然产物研究与开发 ›› 2024, Vol. 36 ›› Issue (增刊1): 98-112.

• 开发研究 • 上一篇    下一篇

川贝枇杷糖浆的化学成分及止咳作用机制的网络药理学研究

张学建1,2,3,徐   鸿2,张   婷2,吴   雷1,3,简美玲1,3,常丹丹1,3,吴纯洁2,陶飞燕1,3*   

  1. 1四川三联新材料有限公司,成都 610041;2成都中医药大学中医药创新研究院 交叉学科研究院,成都 611137;3四川中烟工业有限责任公司,成都 610066 
  • 出版日期:2024-09-14 发布日期:2024-07-17
  • 基金资助:
    “杏林学者”学科人才科研提升计划(CXTD2018007)

Constituents of Chuanbei Pipa syrup and its mechanism on relieving cough based on network pharmacology

ZHANG Xue-jian1,2,3,XU Hong2,ZHANG Ting2,WU Lei1,3,JIAN Mei-ling1,3,CHANG Dan-dan1,3,WU Chun-jie2,TAO Fei-yan1,3*   

  1. 1Sichuan Sanlian New Material Co.,Ltd.,Chengdu 610041,China;2Innovative Institute of Chinese Medicine and Pharmacy Academy for Interdiscipline,Chengdu Univesity of Traditional Chinese Medicine,Chengdu 611137,China;3Research and Development Centre,China Tobacco Sichuan Industrial Co.,Ltd.,Chengdu 610066,China
  • Online:2024-09-14 Published:2024-07-17

摘要:

本文旨在研究川贝枇杷糖浆(Chuanbei Pipa syrup,CPS)的化学成分及其止咳作用机制。首先,运用小鼠急性咳嗽模型验证CPS的止咳作用并结合ELISA检测了相关炎症因子的释放水平;随后,运用UPLC-MS/MS和GC-MS分析CPS的化学成分并结合网络药理学探讨其止咳作用机制:通过建立药物与疾病交集靶点筛选出核心靶点构建咳嗽-药物-成分-核心靶点网络和核心靶点蛋白-蛋白相互作用网络并进行基因本体论富集(GO)和京都基因与基因组百科全书通路(KEGG)富集,分析CPS止咳的潜在靶点和信号通路。小鼠咳嗽实验结果表明CPS具有显著的止咳作用,可以影响呼吸道炎症因子白介素-10(interleukin-10)和白介素-17A(interleukin-17A)的释放。基于超高效液相色谱-四极杆-静电场轨道阱高分辨质谱(UPLC-Q Exactive Orbitrap-MS)和顶空-固相微萃取-气相-质谱联用技术(HS-SPME-GC-MS)共鉴定出CPS的33种化学成分。网络药理学研究中,一共筛选出152个核心靶点用于构建咳嗽-药物-成分-核心靶点网络和核心靶点蛋白-蛋白相互作用网络。GO分析结果表明CPS主要影响内肽酶活性,蛋白丝氨酸/苏氨酸激酶活性,跨膜受体蛋白激酶活性等,KEGG富集分析表明CPS干预MAPK信号通路,PI3K-Akt信号通路,以及炎症介质对TRP通道的调节。

关键词: 川贝枇杷糖浆, 止咳作用, 药效学验证, 成分分析, 网络药理学

Abstract:

This study aims to investigate the chemical constituents and antitussive mechanism of Chuanbei Pipa syrup (CPS).For the first time,the antitussive effect of CPS was verified using the mouse acute cough model,and the release levels of related inflammatory factors were detected by ELISA.Subsequently,the chemical components of CPS were analyzed by UPLC-MS/MS and GC-MS to explore its antitussive mechanism combined with network pharmacology.By constructing a "cough-drug-core target" network,protein-protein interaction (PPI) network of core targets,and performing gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on the intersection targets of drugs and diseases,potential targets and signaling pathways for the treatment of cough diseases by CPS were screened.The mouse acute cough model tests showed a significant antitussive effect of the syrup.It was also found to affect the release of respiratory pro-inflammatory factors interleukin-10 and interleukin-17A.Based on ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry (UPLC-Q Exactive Orbitrap-MS) and headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS),a total of 33 chemical components were identified in CPS.A total of 152 core targets were selected to construct the cough-drug-core target network and core target PPI network.The GO enrichment analysis revealed activities such as endopeptidase activity,protein serine/threonine kinase activity,and transmembrane receptor protein kinase activity,while the KEGG enrichment analysis showed the MAPK signaling pathway,PI3K-Akt signaling pathway,and regulation of inflammatory mediators on TRP channels.

Key words: Chuanbei Pipa syrup, cough relieving effect, pharmacodynamic validation, constituent analysis, network pharmacology

中图分类号:  R285