摘要
雷公藤为卫矛科雷公藤属传统中药材,具有清热解毒、祛风除湿和活血止痛等功效,用于治疗类风湿性关节炎、肾小球肾炎、肾病综合征、红斑狼疮、疥疮、顽癣等病证。其化学成分多样,其中雷公藤甲素(TP)是雷公藤的主要活性和毒性成分之一,其抗炎、抗肿瘤和免疫抑制等生物活性显著,然而亦存在严重的肝肾功能损伤、生殖系统紊乱等不良反应,同时,TP水溶性差、生物利用度低,通过增加给药剂量提升生物利用度,无疑提高了药物在非靶器官的暴露量,导致不良反应的产生,这些在很大程度上限制了TP的临床应用。基于此,笔者拟通过Web of Science、PubMed和中国知网(CNKI)数据库提取相关数据,归纳整理了近些年TP不良反应的研究,从结构修饰、新型递药系统、配伍等角度梳理减毒研究的进展。结构修饰可通过精准改变TP的化学结构,降低其毒性基团的活性,在保留生物活性的同时,从根源上减少不良反应的产生;新型给药系统能够实现TP的靶向递送,提高药物在靶器官的浓度,降低在非靶器官的暴露,从而增强疗效并减少不良反应。此外,通过与中药复方、单味药或单体配伍在降低TP不良反应的同时也可不同程度地增强药效,具有临床价值。该文通过上述不同角度系统阐释了针对TP不良反应的减毒策略,可为TP生物活性的充分发挥和药物开发提供理论依据。
Tripterygium wilfordii is a traditional Chinese medicinal herb belonging to the genus Tripterygium in the Celastraceae family,which has the effects of clearing heat and detoxifying,dispelling wind and dampness,and invigorating blood circulation to relieve pain,and is used to treat diseases such as rheumatoid arthritis,glomerulonephritis,nephrotic syndrome,lupus erythematosus,scabies,and stubborn tinea.Its chemical composition is diverse.Among them,triptolide(TP)is one of the main active and toxic components of T.wilfordii.It has significant biological activities such as anti-inflammation,anti-tumor,and immunosuppression.However,it causes serious adverse reactions such as liver and kidney function damage and reproductive system disorders.At the same time,TP has poor water solubility and low bioavailability,and the enhancement of bioavailability by increasing the dosage undoubtedly improves the exposure of the drug in non-target organs,leading to the occurrence of adverse reactions,and these largely limit the clinical application of TP.Based on this,this article extracted relevant data from the Web of Science,PubMed,and China National Knowledge Infrastructure(CNKI)databases,summarized the research on the adverse reactions of TP in recent years,and reviewed the progress of toxicity reduction research from the perspectives of structural modification,novel drug delivery systems,and compatibility.Structural modification can precisely alter the chemical structure of TP,reduce the activity of its toxic groups,and retain its biological activity while fundamentally reducing the occurrence of adverse reactions.New drug delivery systems can achieve targeted delivery of TP,increase its concentration in target organs,and reduce its exposure in non-target organs,thereby enhancing therapeutic efficacy and reducing adverse effects.In addition,the combination of TP with Chinese medicine compound,single-flavored Chinese medicine or monomer can reduce the adverse effects of TP and enhance the efficacy to different degrees,which is of clinical value.This paper systematically explains attenuation research from the above three perspectives,aiming to provide a theoretical basis for the full utilization of biological activity and drug development of TP.
作者
王文琛
陈鸣
吴双洁
廖正根
董伟
梁新丽
WANG Wenchen;CHEN Ming;WU Shuangjie;LIAO Zhenggen;DONG Wei;LIANG Xinli(Key Laboratory of Modern Preparation of Traditional Chinese Medicine,Ministry of Education,Jiangxi University of Chinese Medicine,Nanchang 330004,China)
出处
《中国实验方剂学杂志》
北大核心
2025年第16期278-287,共10页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(82160751,82060733)
江西省2024年度研究生创新专项(YC2024-S746)。
关键词
雷公藤甲素
不良反应
新型给药系统
配伍
减毒
结构
生物活性
triptolide
adverse reactions
new drug delivery system
compatibility
attenuation
structure
biological activity
