Integration of transcriptomic and metabolomic analysis of the effects of Centella asiatica in cortical neurons

项目汇总_总体 与衰老相关的挑战，包括情绪变化、睡眠障碍和认知能力下降， 对老年人的生活质量产生不利影响。许多植物制剂被认为可以提高抗逆性。 然而，很少有人在精心设计的临床试验中对这些变化进行评估。理想的临床试验应该使用 一种针对其活性成分进行优化的产品，并调查植物学中适当的措施 在相关目标人群中的疗效。因此，需要进行合理的临床前研究，以确定 植物学的影响，这些影响的机制，以及植物化学成分的调节 这些过程。研究还应确定体内植物学不同成分之间的相互作用 通过植物学靶标结合的生物标志物，化合物在体内的分布，以及 不同人群的反应，例如年龄或性别群体。建议的植物性膳食补充剂 研究中心(BDSRC)将建立一个实验方法和技术管道，以 提供这些关键问题的答案，重点是“增强神经和功能的植物药” 在老龄化中的韧性“。这个研究平台将被用来巩固和扩展我们广泛的初步 关于积雪草的研究，为老年参与者的临床试验做准备。一秒钟 植物学，Withan Somnifera(WS；“ashwagandha”)，具有与CA相似的令人信服的生物学效应 将在研究管道的早期阶段进行检查。该中心的具体目标是：(1)确保 提供可靠的CA和WS，并开发有针对性和无针对性地分析其 植物提取物、血浆和脑组织中的化学成分；(2)研究CA的体内作用 已知的活性化合物对小鼠的认知、睡眠障碍和情绪的影响，并确定体内的生物标志物 与这些作用有关；(3)通过对CA和WS提取物的作用机理和活性成分的研究 有针对性和无针对性的方法，包括成分与生物化学的相关性 活性，代谢组学或转录组学处理的目标组织。这些目标将在以下时间实现 植物核心的协同作用，研究项目1考察CA对认知的活体影响， 睡眠剥夺与情绪及研究项目2探索CA和CA的作用机制及活性成分 用小鼠原代神经元体外培养，小鼠脑片体外培养，果蝇体内培养。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)，即提供研究培训 并为研究生和博士后科学家提供职业发展机会。BDSRC的管道 未来，将包括在俄亥俄州立大学NIH/Layton老龄化和阿尔茨海默氏症中心进行的临床试验。

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.