Botanicals enhancing neurological and functional resilience in aging (BENFRA)

植物药可增强衰老过程中的神经和功能恢复能力 (BENFRA)

• 批准号: 10200678
• 负责人: Amala Soumyanath
• 金额: $ 117.25万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10200678
• 关键词: Achievement; Age; Aging; Alzheimer' s Disease; Ashwagandha; Biological; Biological Markers; Botanical dietary supplements; Botanicals; Brain; Clinical Research; Clinical Trials; Clinical Trials Design; Cognition; Coupled; Crude Extracts; Data; Dose; Drosophila melanogaster; Elderly; Ensure; Funding; Future; Gender; Goals; Gotu kola; Grant; Health; Impaired cognition; In Vitro; Infrastructure; Lead; Link; Liquid Chromatography; Mass Spectrum Analysis; Measures; Methods; Modeling; Moods; Mus; Neurologic; Neurons; Oregon; Participant; Perfusion; Phase; Phase III Clinical Trials; Phytochemical; Plant Extracts; Plasma; Population; Positioning Attribute; Preparation; Process; Quality of life; Quinic Acid; Reporting; Research; Research Activity; Research Institute; Research Personnel; Research Project Grants; Research Training; Resolution; Scientist; Sleep; Sleep Deprivation; Sleep disturbances; Slice; Source; Target Populations; Techniques; Testing; Tissues; Translational Research; Triterpenes; United States National Institutes of Health; Work; age group; analytical method; base; brain tissue; career development; data management; design; efficacy testing; faculty mentor; graduate student; improved; in vivo; loss of function; metabolomics; novel; pre-clinical research; preclinical study; programs; resilience; response; sound; targeted biomarker; transcriptomics; translational study; web site

PROJECT SUMMARY_OVERALL Aging- related challenges, including alterations in mood, sleep disturbances and cognitive decline, have detrimental effects on quality of life for the elderly. Many botanical agents are purported to improve resilience to these changes, yet few have been evaluated in well-designed clinical trials. An ideal clinical trial would use a product optimized for its active constituents, and investigate the botanical for appropriate measures of efficacy in a relevant target population. Sound preclinical research is therefore needed to identify the functional effects of a botanical, mechanisms underlying these effects, and the phytochemical constituents modulating these processes. Studies should also identify interactions between different constituents of botanical, in vivo biomarkers of target engagement by the botanical, distribution of the compounds in the body, and variability of response in different populations e.g. age or gender groups. The proposed Botanical Dietary Supplement Research Center (BDSRC) will establish a pipeline of experimental approaches and techniques required to deliver answers to these critical issues, with a focus on “Botanicals enhancing neurological and functional resilience in aging”. This research platform will be used to consolidate and expand our extensive preliminary studies on Centella asiatica (CA; “gotu kola”), in preparation for a clinical trial in aging participants. A second botanical, Withania somnifera (WS; “ashwagandha”), with compelling reports of similar biological effects to CA will be examined in earlier stages of the research pipeline. The specific aims of the Center are to (1) to ensure a reliable supply of CA and WS and develop methods for targeted and untargeted analysis of their constituents in plant extracts, plasma and brain tissue; (2) to investigate the in vivo effects of CA and currently known active compounds on cognition, sleep disturbance and mood in mice, and identify in vivo biomarkers relating to these effects; (3) to explore mechanisms and active compounds of CA and WS extracts through targeted and untargeted approaches including biochemometric correlations of composition with biological activity, and metabolomics or transcriptomics of treated target tissues. These goals will be achieved by the synergistic interaction of a Botanical Core, Research Project 1 examining in vivo effects of CA on cognition, sleep deprivation and mood and Research Project 2 exploring mechanisms and active compounds of CA and WS using mouse primary neurons in vitro, mouse brain slices ex vivo and Drosophila melanogaster in vivo. An Administrative Core will co-ordinate, guide and disseminate the research activities of the BDSRC, and provide data management and statistical support. It will also coordinate aim (4) which is to provide research training and career development opportunities to graduate students and postdoctoral scientists. The BDSRC’s pipeline will, in future, include clinical trials performed at the NIH/Layton Aging and Alzheimer’s Center at OHSU.

项目summary_overall 与衰老有关的挑战，包括情绪改变，睡眠障碍和认知能力下降，已有 对年长的生活质量的有害影响。许多植物剂被称为提高弹性 在这些变化中，在精心设计的临床试验中很少评估。理想的临床试验将使用 针对其活性宪法进行优化的产品，并研究植物学以适当测量 相关目标人群的有效性。因此，需要声音临床前研究来识别功能 植物性的效果，这些作用的基础机制，物理构成调节 这些过程。研究还应确定植物，体内不同构成之间的相互作用 通过植物学，化合物分布的靶标参与生物标志物以及可变性 不同人群的反应，例如年龄或性别群体。拟议的植物饮食补充剂 研究中心（BDSRC）将建立一个实验方法和技术的管道。 为这些关键问题提供答案，重点是“增强神经和功能的植物会 衰老中的韧性”。该研究平台将用于巩固和扩展我们广泛的初步 对Centella Asiatica（CA；“ Gotu Kola”）的研究，为在衰老参与者的临床试验做准备。第二 植物学，withania somnifera（ws;“ ashwagandha”），并具有与CA相似的生物学作用的令人信服的报道 将在研究管道的早期阶段进行检查。中心的具体目的是（1）确保 可靠的CA和WS供应，以及开发针对其目标和非目标分析的方法 构成植物提取物，血浆和脑组织； （2）研究CA和当前的体内效应 小鼠认知，睡眠障碍和情绪的已知活性化合物，并识别体内生物标志物 与这些影响有关； （3）通过CA和WS提取物的机制和活性化合物通过 有针对性和无靶的方法，包括与生物学成分的生物化学相关性 治疗靶组织的活性以及代谢组学或转录组学。这些目标将由 植物核心的协同相互作用，研究项目1研究CA对认知的体内影响， 睡眠剥夺，情绪和研究项目2探索CA和CA的活跃化合物 WS在体外使用小鼠初级神经元，体内的小鼠脑切片和果蝇果蝇。一个 行政核心将协调，指导和传播BDSRC的研究活动，并提供 数据管理和统计支持。它还将协调目标（4），该目标将提供研究培训 和职业发展机会，为研究生和博士后科学家提供了机会。 BDSRC的管道 将来，将包括在NIH/Layton老化和OHSU的阿尔茨海默氏症中心进行的临床试验。