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Demethylzeylasteral Exhibits Strong Inhibition towards UDP-Glucuronosyltransferase (UGT) 1A6 and 2B7

Inhibition of UDP-glucuronosyltransferase (UGT) isoforms can result in severe clinical results, including clinical drug-drug interactions (DDI) and metabolic disorders of endogenous substances. The present study aims to investigate the inhibition of demethylzeylasteral (an important active component...

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Autores principales: Zhao, Jin-Wen, Wang, Gui-Hua, Chen, Min, Cheng, Lian-Hua, Ji, Xiao-Qi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268714/
https://www.ncbi.nlm.nih.gov/pubmed/22874791
http://dx.doi.org/10.3390/molecules17089469
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author Zhao, Jin-Wen
Wang, Gui-Hua
Chen, Min
Cheng, Lian-Hua
Ji, Xiao-Qi
author_facet Zhao, Jin-Wen
Wang, Gui-Hua
Chen, Min
Cheng, Lian-Hua
Ji, Xiao-Qi
author_sort Zhao, Jin-Wen
collection PubMed
description Inhibition of UDP-glucuronosyltransferase (UGT) isoforms can result in severe clinical results, including clinical drug-drug interactions (DDI) and metabolic disorders of endogenous substances. The present study aims to investigate the inhibition of demethylzeylasteral (an important active component isolated from Tripterygium wilfordii Hook F.) towards three important UGT isoforms UGT1A6, UGT1A9 and UGT2B7. The results showed that 100 μM of demethylzeylasteral exhibited strong inhibition towards UGT1A6 and UGT2B7, with negligible influence towards UGT1A9. Furthermore, Dixon and Lineweaver-Burk plots showed the inhibition of UGT1A6 and UGT2B7 by demethylzeylasteral was best fit to competitive inhibition, and the inhibition kinetic parameters (Ki) were calculated to be 0.6 μM and 17.3 μM for UGT1A6 and UGT2B7, respectively. This kind of inhibitory effect need much attention when demethylzeylasteral and demethylzeyasteral-containing herbs (e.g., Tripterygium wilfordii Hook F.) were co-administered with the drugs mainly undergoing UGT1A6, UGT2B7-catalyzed metabolism. However, when extrapolating the in vivo clinical results using our present in vitro data, many complex factors might affect final results, including the contribution of UGT1A6 and UGT2B7 to the metabolism of compounds, and the herbal or patients’ factors affecting the in vivo concentration of demethylzeylasteral.
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spelling pubmed-62687142018-12-12 Demethylzeylasteral Exhibits Strong Inhibition towards UDP-Glucuronosyltransferase (UGT) 1A6 and 2B7 Zhao, Jin-Wen Wang, Gui-Hua Chen, Min Cheng, Lian-Hua Ji, Xiao-Qi Molecules Article Inhibition of UDP-glucuronosyltransferase (UGT) isoforms can result in severe clinical results, including clinical drug-drug interactions (DDI) and metabolic disorders of endogenous substances. The present study aims to investigate the inhibition of demethylzeylasteral (an important active component isolated from Tripterygium wilfordii Hook F.) towards three important UGT isoforms UGT1A6, UGT1A9 and UGT2B7. The results showed that 100 μM of demethylzeylasteral exhibited strong inhibition towards UGT1A6 and UGT2B7, with negligible influence towards UGT1A9. Furthermore, Dixon and Lineweaver-Burk plots showed the inhibition of UGT1A6 and UGT2B7 by demethylzeylasteral was best fit to competitive inhibition, and the inhibition kinetic parameters (Ki) were calculated to be 0.6 μM and 17.3 μM for UGT1A6 and UGT2B7, respectively. This kind of inhibitory effect need much attention when demethylzeylasteral and demethylzeyasteral-containing herbs (e.g., Tripterygium wilfordii Hook F.) were co-administered with the drugs mainly undergoing UGT1A6, UGT2B7-catalyzed metabolism. However, when extrapolating the in vivo clinical results using our present in vitro data, many complex factors might affect final results, including the contribution of UGT1A6 and UGT2B7 to the metabolism of compounds, and the herbal or patients’ factors affecting the in vivo concentration of demethylzeylasteral. MDPI 2012-08-08 /pmc/articles/PMC6268714/ /pubmed/22874791 http://dx.doi.org/10.3390/molecules17089469 Text en © 2012 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Zhao, Jin-Wen
Wang, Gui-Hua
Chen, Min
Cheng, Lian-Hua
Ji, Xiao-Qi
Demethylzeylasteral Exhibits Strong Inhibition towards UDP-Glucuronosyltransferase (UGT) 1A6 and 2B7
title Demethylzeylasteral Exhibits Strong Inhibition towards UDP-Glucuronosyltransferase (UGT) 1A6 and 2B7
title_full Demethylzeylasteral Exhibits Strong Inhibition towards UDP-Glucuronosyltransferase (UGT) 1A6 and 2B7
title_fullStr Demethylzeylasteral Exhibits Strong Inhibition towards UDP-Glucuronosyltransferase (UGT) 1A6 and 2B7
title_full_unstemmed Demethylzeylasteral Exhibits Strong Inhibition towards UDP-Glucuronosyltransferase (UGT) 1A6 and 2B7
title_short Demethylzeylasteral Exhibits Strong Inhibition towards UDP-Glucuronosyltransferase (UGT) 1A6 and 2B7
title_sort demethylzeylasteral exhibits strong inhibition towards udp-glucuronosyltransferase (ugt) 1a6 and 2b7
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6268714/
https://www.ncbi.nlm.nih.gov/pubmed/22874791
http://dx.doi.org/10.3390/molecules17089469
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