Pasinetti: Core B; Biosynthesis and Bioanalytical (Dixon)

摘要/摘要 研究核心B的目的是支持消耗臭氧层物质/NCCAM植物饮食的整体努力 补充研究中心在两个具体领域：(1)通过集中采购、表征、 个别中心使用的多酚材料的存档、质量控制和保质期/稳定性评估 项目；以及(2)集中对所有中心项目和核心的分析和生物合成支持。我们的 以前的研究已经证明，饮食补充剂的显著效果来自于 葡萄籽多酚提取物(GSPE)、协和葡萄汁(CGJ)和白藜芦醇(RSV)促进 在选定的压力条件下保持认知健康和心理弹性。我们还有 研究表明，在血液和大脑中可以检测到大量来自上述植物物质的代谢物。 组织，包括花青素和甲基化和/或葡萄糖醛酸化的各种类别的衍生物 黄酮类(黄烷-3-醇，如儿茶素和表儿茶素；黄酮醇(栎素)；二苯乙烯类(白藜芦醇))。一个 这些化合物中有许多是商业上无法获得的，它们将由以下几种化合物组合而成 合成和生物合成方案的数量足以进行项目1和2中的作用机制研究， 并作为项目1-3研究的标准。其他化合物将在商业上获得，它们的纯度 已验证。因此，核心B的生物合成部分的目的是提供经认证的和 未标记或按要求标记的脑生物可用酚类样品的化学表征 用于作用机制测试的代谢物。B核心的生物分析部分将负责 使用一套分析技术对动物组织中原始和衍生代谢物进行定量 包括液相色谱与紫外检测和质谱仪联用，一维核磁化 核磁共振技术，包括1H核磁共振和13C核磁共振，以及各种2D核磁共振技术，包括1H- 1H TOCSY(总相关光谱)、1H-1H NOESY(核Overhauser增强光谱)、 梯度增强的1H-1H COSY(相关光谱)，1H-13C HSQC(异核单量子 相干)和1H-13C HMBC(异核多键相干)。除了这些生物利用度之外 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储存库， 并执行质量控制分析和稳定性测试，以支持这一功能。互补性 核心B内部的个人调查人员创建了一个强大的协同团队来支持个人项目和 协作努力的重点是实现中心目标。

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.