title: Activation of EpRE-mediated gene transcription by quercetin glucuronides depends on their deconjugation.
abstract: Quercetin is a flavonoid reported to have health-promoting properties. Due to its extensive metabolism to glucuronides in vivo, questions were raised if studies conducted with quercetin aglycone, stating its health-promoting activity, are of actual relevance. Here we show that glucuronides of quercetin, and its methylated forms isorhamnetin and tamarixetin, can induce EpRE-mediated gene expression up to 5-fold. Furthermore, evidence is presented that EpRE-mediated gene induction by these glucuronides involves their deglucuronidation. This indicates that although quercetin-derived glucuronides are the major metabolites present in the systemic circulation, deglucuronidated derivatives are the active compounds responsible for their beneficial EpRE-mediated gene expression effects.
authors: Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands. yhilz@ttz-bremerhaven.de
authors: Yee Y
authors: YY
authors: Lee-Hilz
authors: Maria
authors: M
authors: Stolaki
authors: Willem J H
authors: WJ
authors: van Berkel
authors: Jac M M J G
authors: JM
authors: Aarts
authors: Ivonne M C M
authors: IM
authors: Rietjens
mesh_terms: D001711:Biotransformation; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D017930:Genes, Reporter / Q000235:genetics; D020719:Glucuronides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D011794:Quercetin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D020719:Glucuronides; D011794:Quercetin; D008156:Luciferases; D016660:NAD(P)H Dehydrogenase (Quinone)