The purpose of Core B is to provide a centralized source of Bioanalytical and Bioavailability resources to support individual center projects. Core B is to directly support projects by facilitating characterization of grape derived polyphenol fractions and to determine bioavailability, metabolism and distribution of grapederived polyphenols to target tissues including brain. Core B is critically important for execution of the center projects and employs a wide range of expertise available from Purdue, University of Illinois, and Rutgers associated with the existing Purdue-UAB Botanicals Center. Core B will be divided into Molecular Composition & Bioanalytical and Bioavailability & Metabolism components in order to characterize, archive and assess in vivo bioavailability of grape fractions for individual projects. The Molecular Composition & Bioanalytical Component will provide material authentication and grape polyphenol quantification using the LC/MS methods (Simon and Wu, Rutgers). Following prioritization of specific polyphenol fractions by bioassay guided fractionation, the Core will provide expertise in LC-MS/MS (Simon and Wu, Rutgers) and NMR (Raftery, Purdue) characterization of grape-derived polyphenols in bioactive fractions as well as archiving services for the duration of the project period. (Projects 1 and 3). The Bioavailability & Metabolism Component of Core B will assess grape polyphenol absorption, metabolism and tissue profiles using rodent models, automated blood sampling and membrane probes pioneered by this group (Projects 1,2 and 3, Janle and Weaver, Purdue). The Core will also be responsible for production (Lila, UIUC) and administration (Janle, Purdue) of 14C labeled grape fractions (Projects 1 and 3) followed by analysis of in vivo samples by accelerator mass spectrometry (AMS) techniques to track trace amounts of grape derived polyphenols and their metabolites into target tissues (Project 1,2 and 3). Determination of plasma pharmacokinetics and tissue profiles for unlabeled polyphenols and metabolites will be accomplished by LC-MS/MS and LC-NMR (Projects 1, 2 and 3, Ademec, Raftery and Ferruzzi, Purdue). Analysis of grape polyphenols in target tissues and identification of novel metabolites is fundamental to understanding their biological impact in relation to Alzheimer's pathomechanisms. Information provided by Core B will provide critical knowledge on the fate of grape derived polypohenols associated with modulation of Alzheimer's disease risk and outcomes.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Program Projects (P01)
Project #
5P01AT004511-02
Application #
7677435
Study Section
Special Emphasis Panel (ZAT1)
Project Start
Project End
Budget Start
2008-09-30
Budget End
2009-09-29
Support Year
2
Fiscal Year
2008
Total Cost
$387,508
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Type
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Ho, Lap; Ono, Kenjiro; Tsuji, Mayumi et al. (2018) Protective roles of intestinal microbiota derived short chain fatty acids in Alzheimer's disease-type beta-amyloid neuropathological mechanisms. Expert Rev Neurother 18:83-90
Chen, Tzu-Ying; Ferruzzi, Mario G; Wu, Qing-Li et al. (2017) Influence of diabetes on plasma pharmacokinetics and brain bioavailability of grape polyphenols and their phase II metabolites in the Zucker diabetic fatty rat. Mol Nutr Food Res 61:
Varghese, Merina; Santa-Maria, Ismael; Ho, Lap et al. (2016) Extracellular Tau Paired Helical Filaments Differentially Affect Tau Pathogenic Mechanisms in Mitotic and Post-Mitotic Cells: Implications for Mechanisms of Tau Propagation in the Brain. J Alzheimers Dis 54:477-96
Blount, Jack W; Redan, Benjamin W; Ferruzzi, Mario G et al. (2015) Synthesis and quantitative analysis of plasma-targeted metabolites of catechin and epicatechin. J Agric Food Chem 63:2233-40
Hao, Ke; Di Narzo, Antonio Fabio; Ho, Lap et al. (2015) Shared genetic etiology underlying Alzheimer's disease and type 2 diabetes. Mol Aspects Med 43-44:66-76
Pasinetti, Giulio Maria; Wang, Jun; Ho, Lap et al. (2015) Roles of resveratrol and other grape-derived polyphenols in Alzheimer's disease prevention and treatment. Biochim Biophys Acta 1852:1202-8
Hayden, Eric Y; Yamin, Ghiam; Beroukhim, Shiela et al. (2015) Inhibiting amyloid ?-protein assembly: Size-activity relationships among grape seed-derived polyphenols. J Neurochem 135:416-30
Villani, Tom S; Reichert, William; Ferruzzi, Mario G et al. (2015) Chemical investigation of commercial grape seed derived products to assess quality and detect adulteration. Food Chem 170:271-80
Wang, Dongjie; Ho, Lap; Faith, Jeremiah et al. (2015) Role of intestinal microbiota in the generation of polyphenol-derived phenolic acid mediated attenuation of Alzheimer's disease ?-amyloid oligomerization. Mol Nutr Food Res 59:1025-40
Ho, Lap; Ferruzzi, Mario G; Janle, Elsa M et al. (2013) Identification of brain-targeted bioactive dietary quercetin-3-O-glucuronide as a novel intervention for Alzheimer's disease. FASEB J 27:769-81

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