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Article type: Research Article
Authors: Ferruzzi, Mario G.a; b; * | Lobo, Jessica K.a | Janle, Elsa M.b | Cooper, Brucec | Simon, James E.d | Wu, Qing-Lid | Welch, Carad | Ho, Lape; g | Weaver, Connieb | Pasinetti, Giulio M.e; f; g
Affiliations: [a] Department of Food Science, Purdue University, West Lafayette, IN, USA | [b] Department of Foods and Nutrition, Purdue University, West Lafayette, IN, USA | [c] Bindley Bioscience Center Purdue University, West Lafayette, IN, USA | [d] New Use Agriculture and Natural Plant Products Program (NUANPP), Department of Plant Biology and Plant Pathology, Rutgers University, New Brunswick, NJ, USA | [e] Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA | [f] Department of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA | [g] Geriatric Research and Clinical Center, James J. Peters VA Medical Center, Bronx, NY, USA
Correspondence: [*] Corresponding author: Dr. Mario G. Ferruzzi, Department of Food Science, Purdue University, 745 Agriculture Mall Dr., West Lafayette, IN 47907, USA. Tel.: +1 765 494 0625; Fax: +1 765 494 7953; E-mail: mferruzz@purdue.edu.
Abstract: The present study explored the bioavailability and brain deposition of a grape seed polyphenolic extract (GSPE) previously found to attenuate cognitive deterioration in a mouse model of Alzheimer's disease (AD). Plasma pharmacokinetic response of major GSPE phenolic components was measured following intragastric gavage of 50, 100, and 150 mg GSPE per kg body weight. Liquid chromatography-mass spectrometry (LC-MS) analysis identified gallic acid (GA), catechin (C), and epicatechin (EC) in plasma of rats gavaged acutely with GSPE. Additionally, 4-methylgallic acid (4-OMeGA), 3'-methylcatechin (3'-OMeC), and 3'-methylepicatechin (3'-OMeEC) were identified as circulating metabolites of GSPE phenolic constituents. Cmax for individual GSPE constituents and their metabolites increased in a dose-dependent fashion (with increasing GSPE oral dose). Repeated daily exposure to GSPE was found to significantly increase bioavailability (defined as plasma AUC0-8h) of GA, C, and EC by 198, 253, and 282% relative to animals receiving only a single acute GSPE dose. EC and C were not detectable in brain tissues of rats receiving a single GSPE dose but reached levels of 290.7 ± 45.9 and 576.7 ± 227.7 pg/g in brain tissues from rats administered GSPE for 10 days. This study suggests that brain deposition of GA, C, and EC is affected by repeated dosing of GSPE.
Keywords: Alzheimer's disease, Bioavailability, brain, catechins, gallic acid, grape seed extract, pharmacokinetics
DOI: 10.3233/JAD-2009-1135
Journal: Journal of Alzheimer's Disease, vol. 18, no. 1, pp. 113-124, 2009
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