38934-20-2Relevant articles and documents
Flavonol glycosides of sea buckthorn (hippophae rhamnoides ssp. sinensis) and lingonberry (vaccinium vitis-idaea) are bioavailable in humans and monoglucuronidated for excretion
Lehtonen, Henna-Maria,Lehtinen, Outi,Suomela, Jukka-Pekka,Viitanen, Matti,Kallio, Heikki
, p. 620 - 627 (2010)
Glucuronidation and excretion of sea buckthorn and lingonberry flavonols were investigated in a postprandial trial by analyzing the intact forms of flavonol glycosides as well as glucuronides in plasma, urine, and feces. Four study subjects consumed sea buckthorn (study day 1) and lingonberry (study day 2) breakfasts, and blood, urine, and fecal samples were collected for 8, 24, and 48 h, respectively. Both glycosides and glucuronides of the flavonol quercetin as well as kaempferol glucuronides were detected in urine and plasma samples after the consumption of lingonberries; 14% of flavonols in urine were glycosides, and 86% were glucuronidated forms (wt %). After the consumption of sea buckthorn, 5% of flavonols excreted in urine were detected intact, and 95% as the glucuronides (wt %). Solely glucuronides of flavonols isorhamnetin and quercetin were found in plasma after the consumption of sea buckthorn berries. Only glycosides were detected in the feces after each berry trial. Flavonol glycosides and glucuronides remained in blood and urine quite long, and the peak concentrations appeared slightly later than previously described. The berries seemed to serve as a good flavonol supply, providing steady flavonol input for the body for a relatively long time.
Regiospecific synthesis of quercetin O-β-d-glucosylated and O-β-d-glucuronidated isomers
Kajjout, Mohammed,Rolando, Christian
, p. 4731 - 4741 (2011/07/08)
Quercetin, the polyphenolic compound, which has the highest daily intake, is well known for its protective effects against aging diseases and has received a lot of attention for this reason. Both quercetin 3-O-β-d-glucuronide and quercetin 3′-O-β-d-glucuronide are human metabolites, which, together with their regioisomers, are required for biological as well as physical chemistry studies. We present here a novel synthetic route based on the sequential and selective protections of the hydroxyl functions of quercetin allowing selective glycosylation, followed by TEMPO-mediated oxidation to the glucuronide. This methodology enabled us to synthesize the five O-β-d-glucosides and four O-β-d-glucuronides of quercetin, including the major human metabolite, quercetin 3-O-β-d-glucuronide.
Regioselectivity of phase II metabolism of luteolin and quercetin by UDP-glucuronosyl transferases
Boersma, Marelle G.,Van der Woude, Hester,Bogaards, Jan,Boeren, Sjef,Vervoort, Jacques,Cnubben, Nicole H. P.,Van Iersel, Marlou L. P. S.,Van Bladeren, Peter J.,Rietjens, Ivonne M. C. M.
, p. 662 - 670 (2007/10/03)
The regioselectivity of phase II conjugation of flavonoids is expected to be of importance for their biological activity. In the present study, the regioselectivity of phase II biotransformation of the model flavonoids luteolin and quercetin by UDP-glucuronosyltransferases was investigated. Identification of the metabolites formed in microsomal incubations with luteolin or quercetin was done using HPLC, LC-MS, and 1H NMR. The results obtained demonstrate the major sites for glucuronidation to be the 7-, 3-, 3′-, or 4′-hydroxyl moiety. Using these unequivocal identifications, the regioselectivity of the glucuronidation of luteolin and quercetin by microsomal samples from different origin, i.e., rat and human intestine and liver, as well as by various individual human UDP-glucuronosyltransferase isoenzymes was characterized. The results obtained reveal that regioselectivity is dependent on the model flavonoid of interest, glucuronidation of luteolin and quercetin not following the same pattern, depending on the isoenzyme of UDP-glucuronosyltransferases (UGT) involved. Human UGTIA1, UGTIA8, and UGTIA9 were shown to be especially active in conjugation of both flavonoids, whereas UGTIA4 and UGTIA10 and the isoenzymes from the UGTB family, UGT2B7 and UGT2B15, were less efficient. Due to the different regioselectivity and activity displayed by the various UDP- glucuronosyltransferases, regioselectivity and rate of flavonoid conjugation varies with species and organ. Qualitative comparison of the regioselectivities of glucuronidation obtained with human intestine and liver microsomes to those obtained with human UGT isoenzymes indicates that, in human liver, especially UGT1A9 and, in intestine, UGT1A1 and UGT1A8 are involved in glucuronidation of quercetin and luteolin. Taking into account the fact that the anti-oxidant action as well as the pro-oxidant toxicity of these catechol-type flavonoids is especially related to their 3′,4′-dihydroxyl moiety, it is of interest to note that the human intestine UGT's appear to be especially effective in conjugating this 3′,4′ catechol unit. This would imply that upon glucuronidation along the transport across the intestinal border, the flavonoids loose a significant part of these biological activities.
