Pasinetti: Overall; Dietary Botanicals in the Preservation of Cognitive and Psychological Resilience (Pasinetti)

 描述（由申请人提供）：我们最近在临床前研究中鉴定了特定的富含多酚的植物膳食补充剂[例如，葡萄籽多酚提取物（GSPE）、康科德葡萄汁（CGJ）和白藜芦醇（RSV）]，它们在应激条件下有效促进认知和心理恢复力。拟议的植物膳食补充剂研究中心（BDSRC）的总体目标是从这些生物活性植物补充剂中鉴定出作为其生物活性基础的特定多酚组分，并表征有助于减轻生理应激的特定细胞/分子机制，例如与应激性生活事件相关的机制，其对心理健康，认知功能，最后是幸福（项目1-2）。此外，拟议的研究将首次阐明胃肠道（G）微生物组，特别是人类GI微生物组在调节多酚组分的生物利用度方面的作用，这些多酚组分负责使用人源化“gnotobiotic”小鼠的膳食多酚植物补充剂的认知和心理健康益处（项目3）。因此，拟定的研究（1）表征植物药，（2）在临床前评估其在外周和大脑中的生物利用度和生物活性，同时定义弹性的分子机制，以及（3）确定未来开发临床应用所必需的安全性问题，与NCCAM和ODS的目标完全一致，如RFA的研究目标所示。BDSRC的拟议研究将通过制定严格的科学计划来提高科学知识和技术能力，将提供培训和职业发展机会，并且，至关重要的是，将对膳食多酚植物补充剂在维持和促进心理和认知恢复力方面的作用进行严格的智力检查。

 DESCRIPTION (provided by applicant): We recently identified, in preclinical studies, specific polyphenol-rich botanical dietary supplements [e.g., grape seed polyphenol extract (GSPE), Concord grape juice (CGJ), and resveratrol (RSV)] that are effective in promoting cognitive and psychological resilience under stress conditions. The overall goal of the proposed Botanical Dietary Supplement Research Center (BDSRC) is to identify the specific polyphenol components from these bioactive botanical supplements that underlie their bioactivities and to characterize specific cellular/molecular mechanisms contributing to the attenuation of physiological stress, such as that associated to stressful life events, that have detrimental impact on psychological health, cognitive functions, and ultimately wellbeing (Projects 1-2). In addition the proposed studies will, for the first time, clarify the role of the gastrointestinal (G) microbiome, particularly the human GI microbiome, in modulating the bioavailability of polyphenol components responsible for the cognitive and psychological health benefits of dietary polyphenol botanical supplements using humanized "gnotobiotic" mice (Project 3). Thus, the proposed studies, which (1) characterize botanicals, (2) assess, pre-clinically, their bioavailability and bioactivity in the periphery and in the brain, while defining molecular mechanisms of resilience, and (3) identify safety issues essential for future development into clinical application, are in full alignment with the goals of NCCAM and ODS, as indicated in the Research Objectives of the RFA. The proposed studies in this BDSRC will improve scientific knowledge and technical capabilities through the development of a rigorous scientific program, will provide training and career development opportunities, and, critically, will provide an intellectually rigorous examination of the role of dietary polyphenol botanical supplements in the maintenance and promotion of psychological and cognitive resilience.