Pasinetti: Core B; Biosynthesis and Bioanalytical (Dixon)

总结/摘要 研究核心B的目的是支持ODS/NCCAM植物膳食的总体工作。 补充研究中心在两个具体方面：（1）通过集中采购，定性， 各中心使用的多酚材料的存档、质量控制和有效期/稳定性评估 项目;和（2）通过集中分析和生物合成支持所有中心项目和核心。我们 先前的研究已经证明了从以下组合中进行膳食补充的显著功效： 葡萄籽多酚提取物（GSPE）、康科德葡萄汁（CGJ）和白藜芦醇（RSV） 在选定的压力条件下保持认知健康和心理弹性。我们还 表明在血液和大脑中可以检测到由上述植物产生的许多代谢物 包括花青素和各种类型的花青素的甲基化和/或葡萄糖醛酸化衍生物的组织。 类黄酮（黄烷-3-醇，如儿茶素和表儿茶素;黄酮醇（槲皮素）;芪（白藜芦醇））。一 这些化合物中的许多是不可商购的，并且将通过以下物质的组合产生： 合成和生物合成方案，数量足以进行项目1和2的作用机制研究， 并作为项目1-3研究的标准。其他化合物将通过商业途径获得，其纯度 验证.因此，核心B的生物合成组分的目的是提供经认证的和 化学表征的未标记或放射性标记的脑生物可利用酚类样品（如要求） 代谢物用于作用机制测试。核心B的生物分析组件将负责 使用一套分析技术定量动物组织中的原始和衍生代谢物 包括液相色谱-紫外检测器和质谱法，一维核磁共振， 核磁共振（NMR）技术，包括1H NMR和13 C NMR，以及各种2D NMR技术，包括1H- 1H TOCSY（总相关光谱），1H-1H NOESY（核奥弗豪泽增强光谱）， 梯度增强1H-1H COSY（相关光谱）、1H-13 C HSQC（异源单量子 相干性）和1H-13 C HMBC（杂原子多重键相干性）。除了这些生物利用度 研究，核心B将作为整个中心使用的所有多酚化合物的存档库， 并进行质量控制分析和稳定性测试，以支持这一职能。具有互补性 核心B中的个体研究者创建了一个强大的协同团队来支持个体项目， 共同努力实现中心目标。

Summary/Abstract 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.