The purpose of Research Core B is to support the overall effort of the ODS/NCCAM Botanical Dietary Supplement Research Center in two specific areas: (1) by centralizing the procurement, characterization, archiving, quality control and shelf-life/stability assessment of polyphenolic materials used by individual Center projects; and (2) by centralizing analytical and biosynthesis support for all center projects and cores. Our previous studies have demonstrated the remarkable efficacy of dietary supplementation from a combination of grape seed polyphenolic extract (GSPE), Concord grape juice (CGJ), and resveratrol (RSV) in promoting preservation of cognitive wellness and psychological resiliency under select stress conditions. We have also shown that a number of metabolites arising from the above botanicals can be detected in blood and brain tissues including anthocyanins and methylated and/or glucuronidated derivatives of the various classes of flavonoids (flavan-3-ols such as catechin and epicatecin; flavonols (quercetin); stilbenes (resveratrol)). A number of these compounds are not commercially available, and will be generated by a combination of synthetic and biosynthetic schemes in quantities sufficient for mechanism of action studies in Projects 1 and 2, and as standards for studies in Projects 1-3. Other compounds will be obtained commercially and their purity validated.
The aim of the Biosynthetic Component of Core B is therefore the provision of authenticated and chemically characterized samples of unlabeled or, where requested, radiolabeled, brain-bioavailable phenolic metabolites for mechanism of action testing. The Bioanalytical Component of Core B will be responsible for the quantitation of the original and derived metabolites in animal tissues, using a suite of analytical techniques including liquid chromatography coupled to UV detection and mass spectrometry, 1D nuclear magenetic resonance (NMR) techniques including 1H NMR and 13C NMR, and various 2D NMR techniques including 1H- 1H TOCSY (total correlated spectroscopy), 1H-1H NOESY (nuclear Overhauser enhancement spectroscopy), gradient enhanced 1H-1H COSY (correlated spectroscopy), 1H-13C HSQC (heteronuclear single quantum coherence), and 1H-13C HMBC (heteronuclear multiple bond coherence). In addition to these bioavailability studies, Core B will serve as an archived repository of all polyphenolic compounds used throughout the Center, and perform quality control analyses and stability testing in support of this function. The complementary nature of individual investigators within Core B creates a strong synergistic team to support individual projects and collaborative efforts focused on achieving center objectives.
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