Abstract

The circadian clock is the biological mastermind governing orderly execution of bodily processes throughout the day. In recent years, an emerging topic of broad interest is clock-modulatory agents, including small molecules both of synthetic and natural origins, and their potential applications in disease models. Nobiletin is a naturally occurring flavonoid with the greatest abundance found in citrus peels. Extensive research has shown that Nobiletin is endowed with a wide range of biological activities, yet its mechanism of action remains unclear. We recently found through unbiased chemical screening that Nobiletin impinges on the clock machinery to activate temporal control of downstream processes within the cell and throughout the body. Using animal models of diseases and aging, we and others illustrate potent beneficial effects of Nobiletin on cellular energetics in both periphery and brain to promote healthy aging. Given its excellent safety profile, Nobiletin may represent a promising candidate molecule for development of nutraceutical and chronotherapeutic agents against chronic and age-related neurodegenerative diseases.

中文翻译：

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Nobiletin：以昼夜节律网络为目标，促进生物能量学和健康老龄化

摘要

生物钟是控制全天有序执行身体过程的生物主脑。近年来，一个引起广泛关注的新兴话题是时钟调节剂，包括合成和天然来源的小分子，以及它们在疾病模型中的潜在应用。Nobiletin 是一种天然存在的类黄酮，在柑橘皮中含量最高。大量研究表明，Nobiletin具有广泛的生物活性，但其作用机制尚不清楚。我们最近通过无偏见的化学筛选发现，Nobiletin 会影响时钟机制，以激活对细胞内和整个身体下游过程的时间控制。使用疾病和衰老的动物模型，我们和其他人说明了 Nobiletin 对外周和大脑细胞能量学的有效有益作用，以促进健康衰老。鉴于其出色的安全性，Nobiletin 可能代表一种有前途的候选分子，用于开发针对慢性和年龄相关的神经退行性疾病的营养药物和时间治疗药物。