天然产物研究与开发 ›› 2023, Vol. 35 ›› Issue (4): 592-601.doi: 10.16333/j.1001-6880.2023.4.005

• 研究论文 • 上一篇    下一篇

基于斑马鱼模型和动态分子对接技术探讨西洋参抗缺氧作用及潜在靶点

马智慧1,2,董   榕2,赵焕新2,刘慧茹1,2,丛媛青2,韩欣颖2,李正国1,3*,韩利文2*   

  1. 1山东中医药大学药学院,济南 250355;2山东第一医科大学(山东省医学科学院)药学与制药科学学院,济南 250000;3山东省济宁市食品药品检验检测研究院,济宁 272027
  • 出版日期:2023-04-24 发布日期:2023-04-24
  • 基金资助:
    中央本级重大增减支项目(2060302-1907-09);山东第一医科大学学术提升计划(2019LJ003);山东省农业科技资金(园区产业提升工程)项目(2019YQ033)

Exploring the anti-hypoxic effects and potential targets of American ginseng based on zebrafish model and dynamic molecular docking techniques

MA Zhi-hui1,2,DONG Rong2,ZHAO Huan-xin2,LIU Hui-ru1,2,CONG Yuan-qing2,HAN Xin-ying,LI Zheng-guo1,3*,HAN Li-wen2*   

  1. 1Shandong University of Traditional Chinese Medicine,Jinan 250355,China;2School of Pharmacy and Pharmaceutical Sciences,Shandong First Medical University (Shandong Academy of Medical Sciences),Jinan 250000,China;3Jining Food and Drug Inspection and Testing Research Institute,Jining 272027,China
  • Online:2023-04-24 Published:2023-04-24

摘要:

本研究利用斑马鱼模型和动态分子对接技术研究西洋参抗缺氧(hypoxia)的作用及潜在靶点。以AB系斑马鱼为实验动物,无水硫酸钠为造模剂诱导形成斑马鱼幼鱼缺氧模型,综合评价西洋参的抗缺氧作用。借助网络药理学技术筛选西洋参活性成分以及缺氧相关共有靶点;并使用STRING平台和Cytoscape 3.8.2软件构建蛋白-蛋白作用网络图,寻找西洋参抗缺氧可能的潜在靶点;利用动态分子对接技术验证活性成分与关键靶点的结合能力和稳定性。斑马鱼体内实验显示,西洋参提取物可明显增加斑马鱼在缺氧条件下的存活率,减轻因缺氧导致的神经行为状态(P<0.05),且呈剂量依赖性相关。共筛选获得西洋参7个潜在活性成分和5个抗缺氧潜在靶点;动态分子对接结果显示,西洋参关键活性成分与靶点之间有良好的结合能力,其中TNF、HSP90AA1与活性成分稳定结合,可能为西洋参抗缺氧的关键潜在靶点。综上,本实验建立的斑马鱼幼鱼抗缺氧模型可以快速简便地评价西洋参样品的抗缺氧活性,动态分子对接的结果显示该作用可能通过TNF以及HSP90AA1等靶点发挥作用,为后续西洋参抗缺氧机制研究提供了参考依据。

关键词: 西洋参, 缺氧, 动态分子对接, 斑马鱼, 作用靶点

Abstract:

This study investigated the anti-hypoxia effect and potential targets of American ginseng using zebrafish model and dynamic molecular docking technique.Zebrafish of the AB line were used as experimental animals,and anhydrous sodium sulfate was used as a modeling agent to induce hypoxia in juvenile zebrafish,and the anti-hypoxia effects of American ginseng were comprehensively evaluated.The active ingredients and hypoxia-related common targets of American ginseng were screened by the network pharmacology technique,and the protein-protein interaction network was constructed by STRING platform and Cytoscape 3.8.2 software to find the potential targets of the anti-hypoxia effect of American ginseng,and the binding ability and stability of the active ingredients to the key targets were verified by dynamic molecular docking technique.In vivoexperiments on zebrafish showed that the extract of American ginseng significantly increased the survival rate under hypoxic conditions and reduced the neurobehavioral state caused by hypoxia (P < 0.05),and showed a dose-dependent correlation.Dynamic molecular docking results showed that total seven potential active compounds had good spontaneous binding ability with five potential anti-hypoxic targets,among which TNF,HSP90AA1 might be the key potential targets of American ginseng against hypoxia.In summary,The anti-hypoxia model of zebrafish larvae established in this experiment can quickly and easily evaluate the anti-hypoxia activity of American ginseng samples,and the results of dynamic molecular docking showed that the effect may work through TNF and HSP90AA1 targets,which provides a reference basis for the subsequent study of the anti-hypoxia mechanism of American ginseng.

Key words: American ginseng, hypoxia, dynamic molecular docking, zebrafish, target of action

中图分类号:  R285