Date of Award

Fall 2013

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Nutrition Science

First Advisor

Elsa M. Janle

Committee Chair

Elsa M. Janle

Committee Member 1

Mario G. Ferruzzi

Committee Member 2

John Burgess

Committee Member 3

Jean- Christophe Rochet

Abstract

Consumption of fruits and vegetables has been associated with neuroprotection and cognitive benefits throughout the life span. These associations have sparked interest in plant-derived polyphenols as biologically active agents with potential for targeting brain benefits. However, little is known regarding the ability of the polyphenols or their metabolites from polyphenol-rich products to cross the blood-brain-barrier, and be available for biological action. Furthermore, additional insight is needed on factors affecting the absorption and brain distribution of polyphenol metabolites in vivo. To fill gap in current knowledge, this thesis will focus on the effects of diabetogenic diet and diabetic state which have been considered potential risk factors for neurodegenerative disease on polyphenol bioavailability from a `Standardized Grape Polyphenol' (grape seed extract, Concord grape juice and resveratrol). Additionally, this thesis will provide novel evidence on plasma pharmacokinetics and regional brain distribution of polyphenol metabolites from apple/grape seed and bilberry extracts in a weaning piglet model.

We have found that background diabetogenic diet had limited effects on polyphenol plasma levels and brain bioavailability in a healthy Sprague-Dawley rat model. However, the diabetic state negatively influenced polyphenol metabolite levels in plasma and brain tissues, possibly in part, due to excessive excretion in urine. By using a young piglet model, we determined plasma pharmacokinetics of polyphenol metabolites using physiological and pharmacological doses of apple/grape seed and bilberry extracts. We found that in a physiological dose achievable by supplementation, polyphenol metabolites were able to cross blood-brain barrier to deposit in the brain. There was a difference in regional brain deposition with cerebellum being a preferred site for accumulation. Our data warrant the future design of functional tests on aging-related diseases, specifically Alzheimer's disease as well as improvement in cognitive and memory in healthy infant/child model.

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