4.7 Article

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

期刊

MOLECULAR NUTRITION & FOOD RESEARCH
卷 61, 期 10, 页码 -

出版社

WILEY
DOI: 10.1002/mnfr.201700111

关键词

Bioavailability; Brain; Diabetes; Grape polyphenols; Pharmacokinetics

资金

  1. U.S. National Institutes of Health [PO1 AT004511]
  2. NCCIH [P50 AT008661-01]
  3. ODS

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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 24h, a second dose of SGP was administered and 1h later animals were sacrificed and brain tissue was harvested. Plasma, urine, and brain tissue were analyzed for grape polyphenols. ZDF rats exhibited significantly diminished C-max 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.

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