Influence of Diabetes on Plasma Pharmacokinetics and Brain Bioavailability of Grape Polyphenols in the Zucker Rat Model

Abstract

Grape polyphenols (GP) have been demonstrated to prevent Alzheimer's disease (AD) in a mouse model. Patients with diabetes mellitus are at greater risk of developing AD than non‐diabetic patients. To investigate the effect of the diabetic condition on bioavailability and brain distribution of flavan‐3‐ols, flavonols, and anthocyanins, Zucker diabetic fatty (ZDF) rats and their lean control (LN) were dosed orally with a combination of GP from grape seed extract, Concord grape juice and resveratrol (RES). Eight hour plasma pharmacokinetics was conducted after oral gavage of GP or water for 10 days. LC‐MS/MS analysis identified 3‐glucuronide (3‐glucur) and 3′‐methylglucuronide (3′‐OMe‐glucur) as the main metabolites for catechin (C), epicatechin (EC), quercetin (Q), and RES present in plasma and brains. ZDF rats exhibited significantly diminished maximum plasma concentrations for all above metabolites. ZDF rats showed significantly lower bioavailability by 77%, 79% and 45% in 3′‐OMeC‐glucur, 3′‐OMeEC‐glucur and RES‐3‐glucur relative to the LN. ZDF rats exhibited significantly lower levels than LN in all above metabolites except for Q‐3‐glucur in brain tissues. This study showed that the diabetic condition may impact absorption and distribution of polyphenols, suggesting that dosages required to reach therapeutic efficacy may need to be adjusted for disease condition.Grant Funding Source: NIH Grant P01AT004511