中药化学成分对UGT1A1表达调控及活性作用研究进展(1)
[摘要]尿苷二磷酸葡萄糖醛酸转移酶1A1(UGT1A1)是一种重要的Ⅱ相代谢酶，不仅介导了大量临床药物、非药外源物的代谢清除，同时还在维系机体内源性物质代谢平衡中发挥着至关重要的作用。UGT1A1表达/功能的改变不仅会引起药物/中药-药物相互作用，还可导致内源性物质的代谢紊乱，引发高胆红素血症、胆红素脑病及肝损伤等毒副作用。目前已发现多种临床药物及中药成分等外源物可调控UGT1A1的活性。该文结合国内外在药物代谢及毒理学相关领域新近研究进展，综述了不同类型中药化学成分(如黄酮类、香豆素类、生物碱类等)对UGT1A1表达调控及活性作用，包括中药化学成分对UGT1A1酶活性的抑制作用和中药化学成分对UGT1A1酶的诱导作用。该文能够为UGT1A1介导的中药-药物相互作用提供深入的理解和一定的参考，有助于未来指导临床上中药制剂的合理使用。
[关键词]尿苷二磷酸葡萄糖醛酸转移酶1A1(UGT1A1)； 中药成分； 抑制； 诱导
[Abstract]Uridine 5′-diphosphate-glucuronosyltransferase1A1(UGT1A1) is a major phase Ⅱ metabolism enzyme， responsible for glucuronidation and elimination of drugs and endogenous compounds， playing a vital role in sustaining endogenous metabolism balance. Therefore， changes in UGT1A1 expression/functional can not only cause adverse clinical drug/herbs-drug interactions， but also lead to metabolic disorder of endogenous substances， causing high blood bilirubin， bilirubin encephalopathy and liver injury， as well as other side effects. To date， many studies have found that a variety of clinical medicines and medicinal ingredients can regulate UGT1A1 activity. This article would summarize the advances in research on drug metabolism and toxicology in domestic and foreign literature， and investigate the regulatory effects of different types of traditional Chinese medicine(TCM) ingredients(such as flavonoids， coumarins， alkaloids) on UGT1A1 expression and activity， including inhibitory effect of TCM chemical ingredients on UGT1A1 and effect of TCM chemical ingredients on UGT1A1. It is hoped that this review could provide depth understanding and certain reference for the interaction between chemical ingredients of TCM and UGT1A1， which is of great significance to guide the rational clinical use in future.
, http://www.100md.com
[Key words]UGT1A1； chemical ingredients of traditional Chinese medicine； inhibition； induction
尿苷二磷酸葡萄糖醛酸轉移酶(UDP-glucuronosyltransferases，UGTs)可将许多内源性物质及外源性致癌物、药物、微量元素等转化成葡萄糖醛酸化代谢产物，随胆汁和尿液排出体外[1]。基于氨基酸序列的同源性和基因结构的相似性，人体UGTs通常分为4个家族，UGT1，UGT2，UGT3，UGT8，其中UGT1，UGT2 2个家族是最重要的参与结合反应的药物代谢酶[2]。众多UGTs亚型中，UGT1A1在代谢防御体系和内源性物质稳态中都扮演着非常重要的角色，代谢许多临床“高频”药物(如对乙酰氨基酚，丁丙诺啡，恩他卡朋，依托泊甙，伊力替康等)、“高频”非药外源物(如中草药成分、食品化学成分、致癌物质、环境毒物等)及机体“高危”内源性物质(如胆红素，雌二醇，甾体激素，炎症介质及胆汁酸等)。因此UGT1A1表达、活性及功能的改变不仅能够导致UGT1A1代谢的临床药物在人体内的血浆药物浓度降低或升高进而导致药效的缺失/减少或毒性作用的产生引起临床上不良的药物/中药-药物相互作用，还能够导致内源性物质的代谢紊乱，引发高胆红素血症、胆红素脑病及肝损伤等毒副作用[3-6]。目前已发现多种临床用药(如利喘平、茚地那韦、索拉菲尼等)及中药成分(如补骨脂中主要活性成分、黄酮类及人参皂苷类等)等外源物可抑制或诱导UGT1A1进而调控其活性。美国食品药物管理局(FDA)在药物-药物相互作用研究指南中明确指出，在研究药物-药物之间相互作用时必须明确药物与UGT1A1之间的作用关系。, 百拇医药(辛红 徐巍)
[关键词]尿苷二磷酸葡萄糖醛酸转移酶1A1(UGT1A1)； 中药成分； 抑制； 诱导
[Abstract]Uridine 5′-diphosphate-glucuronosyltransferase1A1(UGT1A1) is a major phase Ⅱ metabolism enzyme， responsible for glucuronidation and elimination of drugs and endogenous compounds， playing a vital role in sustaining endogenous metabolism balance. Therefore， changes in UGT1A1 expression/functional can not only cause adverse clinical drug/herbs-drug interactions， but also lead to metabolic disorder of endogenous substances， causing high blood bilirubin， bilirubin encephalopathy and liver injury， as well as other side effects. To date， many studies have found that a variety of clinical medicines and medicinal ingredients can regulate UGT1A1 activity. This article would summarize the advances in research on drug metabolism and toxicology in domestic and foreign literature， and investigate the regulatory effects of different types of traditional Chinese medicine(TCM) ingredients(such as flavonoids， coumarins， alkaloids) on UGT1A1 expression and activity， including inhibitory effect of TCM chemical ingredients on UGT1A1 and effect of TCM chemical ingredients on UGT1A1. It is hoped that this review could provide depth understanding and certain reference for the interaction between chemical ingredients of TCM and UGT1A1， which is of great significance to guide the rational clinical use in future.
, http://www.100md.com
[Key words]UGT1A1； chemical ingredients of traditional Chinese medicine； inhibition； induction
尿苷二磷酸葡萄糖醛酸轉移酶(UDP-glucuronosyltransferases，UGTs)可将许多内源性物质及外源性致癌物、药物、微量元素等转化成葡萄糖醛酸化代谢产物，随胆汁和尿液排出体外[1]。基于氨基酸序列的同源性和基因结构的相似性，人体UGTs通常分为4个家族，UGT1，UGT2，UGT3，UGT8，其中UGT1，UGT2 2个家族是最重要的参与结合反应的药物代谢酶[2]。众多UGTs亚型中，UGT1A1在代谢防御体系和内源性物质稳态中都扮演着非常重要的角色，代谢许多临床“高频”药物(如对乙酰氨基酚，丁丙诺啡，恩他卡朋，依托泊甙，伊力替康等)、“高频”非药外源物(如中草药成分、食品化学成分、致癌物质、环境毒物等)及机体“高危”内源性物质(如胆红素，雌二醇，甾体激素，炎症介质及胆汁酸等)。因此UGT1A1表达、活性及功能的改变不仅能够导致UGT1A1代谢的临床药物在人体内的血浆药物浓度降低或升高进而导致药效的缺失/减少或毒性作用的产生引起临床上不良的药物/中药-药物相互作用，还能够导致内源性物质的代谢紊乱，引发高胆红素血症、胆红素脑病及肝损伤等毒副作用[3-6]。目前已发现多种临床用药(如利喘平、茚地那韦、索拉菲尼等)及中药成分(如补骨脂中主要活性成分、黄酮类及人参皂苷类等)等外源物可抑制或诱导UGT1A1进而调控其活性。美国食品药物管理局(FDA)在药物-药物相互作用研究指南中明确指出，在研究药物-药物之间相互作用时必须明确药物与UGT1A1之间的作用关系。, 百拇医药(辛红 徐巍)