strong inhibition of celastrol towards udp-glucuronosyl transferase (ugt) 1a6 and 2b7 indicating potential risk of ugt-based herb-drug interaction强烈抑制celastrol向udp-glucuronosyl转移酶(ugt)1 a6和2 b7指示潜在的风险ugt-based herb-drug交互.pdfVIP

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strong inhibition of celastrol towards udp-glucuronosyl transferase (ugt) 1a6 and 2b7 indicating potential risk of ugt-based herb-drug interaction强烈抑制celastrol向udp-glucuronosyl转移酶(ugt)1 a6和2 b7指示潜在的风险ugt-based herb-drug交互.pdf

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strong inhibition of celastrol towards udp-glucuronosyl transferase (ugt) 1a6 and 2b7 indicating potential risk of ugt-based herb-drug interaction强烈抑制celastrol向udp-glucuronosyl转移酶(ugt)1 a6和2 b7指示潜在的风险ugt-based herb-drug交互

Molecules 2012, 17, 6832-6839; doi:10.3390/molecule OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Strong Inhibition of Celastrol Towards UDP-Glucuronosyl Transferase (UGT) 1A6 and 2B7 Indicating Potential Risk of UGT-Based Herb-Drug Interaction Yong-Sheng Zhang †,*, Yan-Yang Tu †, Xing-Chun Gao, Jun Yuan, Gang Li, Liang Wang, Jian-Ping Deng, Qi Wang and Ru-Meng Ma Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, Shaanxi, China † These authors contributed equally to this work. * Author to whom correspondence should be addressed; E-Mail: zhangyongsheng979@; Tel.: +86-298-477-7001. Received: 27 April 2012; in revised form: 25 May 2012 / Accepted: 25 May 2012 / Published: 5 June 2012 Abstract: Celastrol, a quinone methide triterpene isolated from Tripterygium wilfordii Hook F., has various biochemical and pharmacological activities, and is now being developed as a promising anti-tumor agent. Inhibitory activity of compounds towards UDP-glucuronosyltransferase (UGT) is an important cause of clinical drug-drug interactions and herb-drug interactions. The aim of the present study is to investigate the inhibition of celastrol towards two important UDP-glucuronosyltransferase (UGT) isoforms UGT1A6 and UGT2B7. Recombinant UGT isoforms and non-specific substrate 4-methylumbelliferone (4-MU) were used. The results showed that celastrol strongly inhibited the UGT1A6 and 2B7-mediate