Structures of (−)-epicatechin glucuronide identified from plasma and urine after oral ingestion of (−)-epicatechin: differences between human and rat

(–)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans

“…2, the most abundant metabolites determined after the ingestion of f lavanol-rich cocoa were 4Ј-O-methyl-epicatechin-O-␤-Dglucuronides. In agreement with previously published data (16), and based on authentic standards as well as verifying analytical procedures (please refer to Supporting Materials and Methods, which is published as supporting information on the PNAS web site), we have identified various isomers of 4Ј-O-methyl-epicatechin-O-␤-Dglucuronide with glucuronidation in positions 7, 5, and 3Ј of the flavanol structure, of which derivatizations in positions 7 and 5 were more common. For the purpose of this investigation, we have not distinguished between structurally distinct isomers of 4Ј-O-methylepicatechin-O-␤-D-glucuronide.…”

“…The reasons for these shortcomings are, at least in part, based on the fact that food matrices contain a multitude of phytochemical constituents, of which an unknown number may exert physiological effects. Furthermore, despite the fact that previous work structurally characterized major flavanol metabolites in human plasma (16)(17)(18)(19), the direct proof that, and which of, the absorbed flavanols and their metabolites are causally linked to the observed cardiovascular effects in humans has yet to be established. Importantly, most data available from in vitro studies are based on the use of flavanol forms as present in foods and not as they exist in circulation, potentially limiting the validity of a subsequent data analysis in the context of human physiology.…”

“…Importantly, most data available from in vitro studies are based on the use of flavanol forms as present in foods and not as they exist in circulation, potentially limiting the validity of a subsequent data analysis in the context of human physiology. The extent of this potential drawback becomes apparent when considering that the human metabolism of flavanols gives rise to various O-methylated, O-glucuronidated, and Osulfated flavanol derivatives that are products of phase I͞II biotransformation in intestine and liver (16)(17)(18)(19). Flavanols also undergo biotransformation by the gut micro flora resulting in a large variety of phenolic acid derivatives and ␥-valerolactone-like compounds (20).…”

Structural Modifications at the C-4 Position Strongly Affect the Glucuronidation of 6,7-Dihydroxycoumarins

“…It was equally clear that the monoglucuronides of 4-ME, 4-PE, and 4-HME were also 7-O-glucuronides, which could be readily seen from the shifts of the carbon signals of C-7 as well as C-6 and C-8. Moreover, the coupling constants for the anomeric protons of 7-O-glucuronides of esculetin (J = 7.2), 4-ME (J = 7.3), 4-PE (J = 7.2), and 4-HME (J = 7.2) were characteristic of the b-anomers (Natsume et al, 2003).…”

In vitroevaluation of the antioxidant and anti-inflammatory activities of sulphated metabolites of catechins Evaluaciónin vitrode las actividades antioxidante y antiinflamatoria de metabolitos sulfatados de catequinas

“…It has been shown that catechins are absorbed from the human intestinal tract, largely metabolised and distributed as conjugated derivatives in bloodstream (Baba et al, 2000). Methyl, sulphate and glucuronide conjugates have been described as circulating metabolites of catechins (Baba, Osakabe, & Natsume, 2001;Donovan et al, 1999Donovan et al, , 2001Natsume et al, 2003). Circulating metabolites would be those able to reach the biological targets and, therefore, they should be main actors to explain the health effects associated to the intake of catechins and flavonoids in general.…”