Botanicals for functional resilience to aging: identifying in vivo biomarkers of the effects of Centella asiatica (Project 1)

具有抗衰老功能的植物药：识别积雪草作用的体内生物标志物（项目 1）

• 批准号: 10661723
• 负责人: Nora Gray
• 金额: $ 42.84万
• 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/10661723
• 关键词: Acids; Affect; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Animals; Anti-Anxiety Agents; Antioxidants; Anxiety; Ayurvedic Medicine; Behavior; Behavior assessment; Behavioral; Biological Markers; Blood; Botanicals; Brain; Brain imaging; Chinese Traditional Medicine; Chronic; Clinical Trials; Clinical Trials Design; Cognition; Cognitive; DNA Methylation; Data; Dopamine; Dose; Drug Kinetics; Elderly; Electroencephalography; F2-Isoprostanes; Failure; Food; Formulation; Future; Goals; Gotu kola; Health; Herb; Hormones; Human; Hydrocortisone; Impaired cognition; In Vitro; Knowledge; Learning; Life; Magnetic Resonance Spectroscopy; Measures; Memory; Mental Depression; Methodology; Methods; Mitochondria; Moods; Mus; Nerve; Neurologic; Neurons; Neurotransmitters; Oral Administration; Pathway interactions; Pattern; Perfusion; Phenotype; Plant Extracts; Plants; Plasma; Population; Prevalence; Psyche structure; Quality of life; Rapid screening; Reporting; Rodent Model; Serotonin; Sleep; Sleep Deprivation; Sleep disturbances; Sleeplessness; Synapses; System; Testing; Traditional Medicine; Translations; Water; affective disturbance; age related; aged; arterial spin labeling; blood perfusion; clinical development; cognitive change; cognitive enhancement; cognitive function; cognitive performance; density; depressive symptoms; dosage; efficacy evaluation; executive function; experimental study; gamma-Aminobutyric Acid; healthy aging; human subject; improved; improvement on sleep; in vivo; in vivo evaluation; metabolomics; methylation pattern; mouse model; peripheral blood; pre-clinical; pre-clinical research; preclinical study; promote resilience; research clinical testing; resilience; response; sleep spindle; targeted biomarker

PROJECT SUMMARY_PROJECT 1 Resilience to aging-related challenges can be the difference between physical and mental decline and a longer, healthier life. The increased prevalence of sleep disturbances, mood alterations and cognitive impairment observed in the elderly population can have substantial effects on quality of life and overall health. Traditional medicine systems have identified numerous botanicals that support health in older adults. Many of these botanicals have compelling preclinical evidence supporting their potential efficacy in humans yet few have been evaluated in well-designed clinical trials. This is due in part to a failure of these preclinical studies to focus on translationally relevant endpoints and biomarkers of efficacy. This project proposes to establish the experimental framework necessary to evaluate a botanical agent with promising in vitro mechanistic results in a mammalian system, in order to generate the data necessary to inform a well-designed clinical trial. This proposal will focus on the resilience-promoting effects of the plant Centella asiatica (L.) Urban. This herb is used in Ayurvedic and traditional Chinese medicine as a nerve tonic and to improve cognitive function. Our lab and others have shown that low doses of the water extract of Centella asiatica (CAW) can improve cognitive function in rodent models of aging and Alzheimer’s disease. Anxiolytic effects and improvement in insomnia as a result of administering the extract have also been reported. However, few clinical trials have attempted to validate these effects and each has suffered from severe methodological flaws such as lack of controls, being underpowered and assessing appropriate biomarkers of efficacy. In this study we will address critical knowledge gaps hindering the clinical development of CAW including proper dosage, optimal product formulation and identification of translational biomarkers. Using aged mice we will explore the effects of a range of CAW doses on cognitive impairment, sleep and resilience to sleep deprivation, and anxiety and depression. Brain imaging, sleep phenotype, as well as circulating hormone levels and blood DNA methylation patterns will all be evaluated as biomarkers for target engagement. We will also determine the effects of constituent compounds from the CAW extract on the same behavioral endpoints in order to inform product formulation to be used in a clinical trial. These experiments will determine the efficacy of CAW as a botanical agent to promote functional resilience to age-related challenges and thereby facilitate its translation to a clinical trial in older adults. Additionally, this study will establish a methodological platform that can be used in future studies with any promising botanical to provide the necessary in vivo testing to move towards clinical testing.

项目摘要项目1