Characterization and bioavailability of neuroprotective grape seed extract in an animal model
Abstract
Grape seed extract (GSE) is a rich source of biologically active phenolics acids and proanthocyanidins (PACs) that are associated with neuroprotective effects. The proposed use of GSE for prevention and/or amelioration of Alzheimer disease (AD) has stimulated interest in understanding the bioavailability and metabolism of individual bioactive phenolic components from crude preparations. The objective of these studies was to characterize bioavailability and metabolism of major GSE components by investigating acute and long-term impact of a specific GSE (MegaNatural AZ) in a Sprague Dawley rat model. Initial plasma pharmacokinetic studies were conducted acutely and following repeated-exposure to GSE (50-150 mg/kg BW) over a 10 day period. LC-MS analysis identified gallic acid (GA), catechin (C), epicatechin (EC) as primary circulating plasma forms of GSE phenolics. Repeated-exposure to GSE significantly improved bioavailability of monomeric catechins and gallic acid in comparison to a single acute dose. More complex oligomeric and polymeric PACs abundant in GSE were not bioavailable. Additionally, C and EC were detected in brain tissues (3 pmol/g) of animals administered GSE for 10d indicating the ability of monomer PACs to cross the blood-brain barrier. To better understand metabolism of GSE components, PACs were fractionated into monomer enriched (MEF) and polymer fractions (PEF) and orally administered to Sprague Dawley rats acutely and following 10d repeated-exposure. Results indicated that C and EC-β-glucuronide and their methylated forms were the major phase II metabolites circulating in plasma and available for accumulation in rodent brain tissue at levels of 41-94 and 84-123 pmol/g tissue following 10d repeated dosing with methylated derivatives accounting for up to 61.2% of the total PACs present. Area under the curve (AUC) and maximum plasma concentration (Cmax) for C and EC metabolites were significantly enhanced (P<0.01) following repeated-exposure (2253 and 1891) compared to single acute treatment (433 and 399). Circulating methylated C and EC metabolites were highest from MEF (1890.5 nmol/L*h) compared to GSE (462.0 nmol/L*h) and PEF (13.8 nmol/L*h) (P<0.05) treated rats. These findings support the notion that monomeric PACs are the primary bioavailable phenolic component from GSE and that absorption and metabolism of monomer PACs may be enhanced by long-term treatment.
Degree
M.S.
Advisors
Ferruzzi, Purdue University.
Subject Area
Food Science|Nutrition
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