Influence of diabetes on plasma pharmacokinetics and brain bioavailability of grape polyphenols and their phase II metabolites in the Zucker diabetic fatty rat.

SCOPE: The effect of diabetes on the pharmacokinetics, bioavailability and brain distribution of grape polyphenols and select metabolites was studied in the Zucker diabetic fatty (ZDF) rat model. METHODS AND RESULTS: (ZDF) rats and their lean controls (LN) were dosed with a Standardized Grape Polyphenol (SGP) Mixture consisting of grape seed extract, Concord grape juice and resveratrol (RES) by oral gavage for 10 days. An 8-h pharmacokinetic study was performed. After 24 h, a second dose of SGP was administered and 1 h later animals were sacrificed and brain tissue was harvested. Plasma, urine, and brain tissue were analyzed for grape polyphenols. ZDF rats exhibited significantly diminished Cmax for all catechin, epicatechin, quercetin and resveratrol conjugated metabolites. Bioavailability was significantly lower in ZDF rats for methylated flavan-3-ol, RES, and quercetin metabolites. Significantly lower levels of metabolites of RES, quercetin, and flavan-3-ols were found in brains of ZDF rats. There was no significant difference between ZDF and LN in anthocyanins in plasma and no anthocyanins were detectable in brain extracts. ZDF rats showed significantly higher urinary excretion for all polyphenols. CONCLUSION: Diabetes may alter the overall bioavailability of some polyphenols in plasma and brain in part due to higher urinary clearance.

Urinary excretion and metabolism of procyanidins in pigs.

SCOPE: Aim of this study was to investigate urinary excretion and metabolism of procyanidins a group of secondary plant metabolites with many beneficial health effects described in literature. METHODS AND RESULTS: To investigate the metabolism of procyanidins in the absence of flavan-3-ols, centrifugal partition chromatography was used for their reduction in a grape seed extract to a level of almost zero. After administration of the monomer reduced grape seed extract (mredGSE) containing procyanidins B1, B2, B3, B4, C1 to pigs flavan-3-ols, their methyl derivatives, dimeric and trimeric procyanidins were determined in urine by high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Maximal concentrations of procyanidins 6 h after administration vary from 5 to 30 ng/mg creatinine. Total excretion of flavan-3-ols and their methyl derivatives indicates an increasing trend for pigs given mredGSE in comparison to pigs of the control group. Flavan-3-ols were conjugated and methylated to a great extent in comparison to dimeric and trimeric procyanidins. In the case of low molecular weight metabolites, an increasing trend was observed for hippuric acid, not for phenolic acids. CONCLUSIONS: Ratios of total excretion of procyanidins to administrated amounts between 0.004% (C1) and 0.019% (B4) suggest a poor urinary excretion by pigs. A transfer of these results to humans is possible due to their similar gastrointestinal tract.