中国药物警戒 ›› 2024, Vol. 21 ›› Issue (12): 1321-1328.
DOI: 10.19803/j.1672-8629.20240700

• 专家论坛 • 上一篇    下一篇

靶点钩钓技术在中药药理与毒理研究中的应用与展望

陈思祎1,2, 生立嵩3,4,5, 孙蓉2,3,*   

  1. 1天津中医药大学中医药研究院,天津 301617;
    2山东大学第二医院基础医学研究所,山东 济南 250033;
    3山东大学高等医学研究院,山东 济南 250012;
    4山东省中医药研究院,山东 济南 250014;
    5鲁南制药有限公司,山东 临沂 276005
  • 收稿日期:2024-09-06 出版日期:2024-12-15 发布日期:2024-12-16
  • 通讯作者: *孙蓉,女,博士,教授·博导,中药药理学与毒理学。E-mail: sunrong107@163.com。山东大学特聘教授,二级教授·博士生导师,高等医学研究院、山东大学第二医院双聘PI;国家“十四五”重点研发计划项目首席科学家,国家中医药高水平重点学科“中药毒理学”学科带头人,第二医院中西医结合医学中心学科带头人;第十四届全国政协委员。从事中药药理毒理研究37年,在中药功效现代表征与药效评价、有毒中药效-毒整合研究、名优方药临床转化与新药研发领域取得一系列创新成果,先后主持完成973、“十一五”重大新药创制专项等课题56项,以第一完成人获山东省科技进步一等奖2项、二等奖2项,首位授权专利22项;牵头研发新药获批临床批件、新药证书17件。2015年获批泰山学者特聘专家等人才称号,2008年获批享受国务院政府特殊津贴;《中国药物警戒》期刊副主编。
  • 作者简介:陈思祎,女,硕士,中药药理学与毒理学。
  • 基金资助:
    国家重点研发计划（2022YFC3502100）; 国家重点研发计划课题五（2022YFC3502105）

Applications of “Target Fishing” Technique in Pharmacological Research of Traditional Chinese Medicine

CHEN Siyi1,2, SHENG Lisong3,4,5, SUN Rong2,3,*   

  1. 1Academy of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China;
    2The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan Shandong 250033, China;
    3Advanced Medical Research Institute, Shandong University, Jinan Shandong 250012, China;
    4Shandong Academy of Chinese Medicine, Jinan Shandong 250014, China;
    5Lunan Pharmaceutical Group Corporation, Linyi Shandong 276005, China
  • Received:2024-09-06 Online:2024-12-15 Published:2024-12-16

PDF (PC)

68

摘要： 目的 综述近年来靶点钩钓技术在中医药领域的应用,针对中药成分复杂、靶点成分不明的现状,探讨靶点钩钓技术在中药药理学、中药毒理学的研究意义,突破机制复杂造成的中医药现代化研究瓶颈。方法 检索近15年来中医药领域靶点钩钓相关文献,总结常用靶点钩钓技术研究方法,分析这些技术在揭示中药药效、毒性靶点方面的研究优势与局限性。结果 目前中医药领域应用的靶点钩钓技术类型以亲和钩钓为主,常与质谱等多种技术联用,用于中药药效成分/毒性成分在明晰效毒机制基础上的直接作用靶点研究。但该技术难以应用于构效关系紧密的小分子或对复杂中药体系进行快速、无偏倚蛋白质靶点鉴定;现有研究对中医药理论的诠释尚薄弱,后续验证研究或深入挖掘方面也缺少与中医药理论的深入融合。结论 靶点钩钓技术从分子层面上为解析中药作用机制提供了新思路、新方法,也为中药“效-毒”整合研究从效毒物质与作用靶点上提供了研究策略,下一步应充分挖掘中医药理论,从整体、系统角度对其研究予以验证与升华,以期为中药“效-毒”整合评价提供科学依据。

关键词: 靶点钩钓技术, 靶点识别, 中药药理学, 中药毒理学, “效-毒”整合

Abstract: Objective To review the recent applications of “target fishing” technique in the fields of Traditional Chinese Medicine (TCM) in recent years in order to contribute to overcoming the bottleneck of TCM modernization caused by the complexity of TCM components and the uncertainty of target components. Methods Literature on “target fishing” techniques in the field of TCM in the past 15 years was searched. Research methods involved in the commonly used “target fishing” techniques were summarized. The strengths and weaknesses of these techniques in revealing the action or toxicity targets of TCM components were analyzed. Results “Target fishing” techniques applied in the field of TCM were mostly based on “affinity fishing”, which was often used in conjunction with liquid chromatography, mass spectrometry and other technologies for direct target research of TCM potent or toxic components on the basis of a clear mechanism of affinity fishing and toxicity. It was difficult to apply this technique to small molecules with close conformational relationships or to perform rapid and unbiased protein target identification for complex TCM systems. The interpretation of TCM theories in existing studies remained weak, and there was a lack of in-depth integration with TCM theories in subsequent validation studies or in-depth excavation. Conclusion The “target fishing” technique offers novel insights and methodologies for elucidating the molecular-level mechanisms of TCM action. This study proposes a research strategy for investigating the effects and toxicity of TCM, which should be thoroughly explored within the framework of TCM theories and substantiated from comprehensive system-level perspectives. The“target fishing” technique provides references for integrated evaluation of the “effect-toxicity” of TCM.

Key words: “Target Fishing” Technique, Identification of Target, Pharmacology of TCM, Toxicology of TCM, Efficacy-Toxicity Components

中图分类号: