靶点钩钓技术在中药药理与毒理研究中的应用与展望  

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

作　　者：陈思祎 生立嵩 孙蓉[2,3] CHEN Siyi;SHENG Lisong;SUN Rong(Academy of Traditional Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;The Second Hospital,Cheeloo College of Medicine,Shandong University,Jinan Shandong 250033,China;Advanced Medical Research Institute,Shandong University,Jinan Shandong 250012,China;Shandong Academy of Chinese Medicine,Jinan Shandong 250014,China;Lunan Pharmaceutical Group Corporation,Linyi Shandong 276005,China)

机构地区：[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

出　　处：《中国药物警戒》2024年第12期1321-1328,共8页Chinese Journal of Pharmacovigilance

基　　金：国家重点研发计划(2022YFC3502100);国家重点研发计划课题五(2022YFC3502105)。

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。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.

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 

分 类 号：R285[医药卫生—中药学] R994.11[医药卫生—中医学]