Tzu-Ying Chen1, Mario G Ferruzzi1,2, Qing-Li Wu3, James E Simon3, Stephen T Talcott4, Jun Wang5, Lap Ho6, George Todd1, Bruce Cooper7, Giulio M Pasinetti6, Elsa M Janle1. 1. Department of Nutrition Science, Purdue University, West Lafayette, Indiana, USA. 2. Department of Food Science, Purdue University, West Lafayette, Indiana, USA. 3. Department of Plant Biology, Rutgers University, New Brunswick, New Jersey, USA. 4. Department of Food Science, Texas A&M University, College Station, Texas, USA. 5. Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA. 6. Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, USA. 7. Bindley Bioscience Center, Purdue University, West Lafayette, Indiana, USA.
Abstract
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.
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. ZDFrats exhibited significantly diminished Cmax for all catechin, epicatechin, quercetin and resveratrol conjugated metabolites. Bioavailability was significantly lower in ZDFrats 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 ZDFrats. There was no significant difference between ZDF and LN in anthocyanins in plasma and no anthocyanins were detectable in brain extracts. ZDFrats 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.
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