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

整合转录组学和代谢组学分析积雪草对皮质神经元的影响

• 批准号: 10377854
• 负责人: Amala Soumyanath
• 金额: $ 12.73万
• 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/10377854
• 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.

项目概要_总体 与衰老相关的挑战，包括情绪改变、睡眠障碍和认知能力下降，已经 对老年人的生活质量产生不利影响。许多植物制剂据称可以提高恢复能力 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。理想的临床试验将使用 针对其活性成分进行优化的产品，并研究植物学以采取适当的措施 在相关目标人群中的功效。因此，需要进行合理的临床前研究来确定其功能 植物药的作用、这些作用的机制以及调节的植物化学成分 这些过程。研究还应该确定植物、体内不同成分之间的相互作用 植物靶标参与的生物标志物、化合物在体内的分布以及化合物的变异性 不同人群的反应，例如年龄或性别群体。拟议的植物膳食补充剂 研究中心（BDSRC）将建立一系列所需的实验方法和技术 为这些关键问题提供答案，重点是“增强神经和功能的植物药” 老龄化复原力”。这个研究平台将用于巩固和拓展我们广泛的前期工作 对积雪草（CA；“gotu kola”）的研究，为老年参与者的临床试验做准备。一秒钟 植物性睡茄（WS；“ashwagandha”），有令人信服的报告称其具有与 CA 相似的生物效应 将在研究管道的早期阶段进行审查。该中心的具体目标是 (1) 确保 可靠的 CA 和 WS 供应，并开发对其进行有针对性和无针对性分析的方法 植物提取物、血浆和脑组织中的成分； (2)研究CA的体内作用，目前 已知的活性化合物对小鼠认知、睡眠障碍和情绪有影响，并鉴定体内生物标志物 与这些影响有关； (3)通过研究CA和WS提取物的作用机制和活性成分 有针对性和无针对性的方法，包括成分与生物的生物化学计量学相关性 活性，以及​​治疗靶组织的代谢组学或转录组学。这些目标将通过 植物核心的协同相互作用，研究项目 1 检查 CA 对认知的体内影响， 睡眠剥夺和情绪研究项目 2 探索 CA 和的机制和活性化合物 WS 在体外使用小鼠原代神经元，在体外使用小鼠脑切片，在体内使用黑腹果蝇。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)，即提供研究培训 以及研究生和博士后科学家的职业发展机会。 BDSRC 的管道 未来，将包括在 OHSU 的 NIH/Layton 衰老和阿尔茨海默病中心进行的临床试验。