Oak extracts modulate circadian rhythms of clock gene expression in vitro and wheel-running activity in mice
Oak extracts modulate circadian rhythms of clock gene expression in vitro and wheel-running activity in mice
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橡树提取物调节体外时钟基因表达的昼夜节律和小鼠的跑轮活动
DOI：
10.1007/s41105-021-00365-2
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发表时间：
2022
影响因子：
1.1
通讯作者：
Shibata Shigenobu
中科院分区：
文献类型：
--
作者：
Haraguchi Atsushi;Du Yao;Shiraishi Rena;Takahashi Yuki;Nakamura Takahiro J.;Shibata Shigenobu
哺乳动物的中枢生物钟位于下丘脑视交叉上核（SCN）内，负责协调昼夜节律和控制运动活动节律。除了SCN细胞，外周组织和胚胎成纤维细胞也有时钟基因，如Per 1/2和Bmal 1，它们产生转录-翻译反馈环，产生大约24小时的周期。衰老对生物钟系统和运动功能产生不利影响。据报道，橡树提取物可以改善与年龄相关的生理变化。然而，没有研究已经研究了橡树提取物对昼夜节律钟system.MethodsWe的影响，橡树提取物及其代谢产物（尿石素A [ESTA]和鞣花酸[EA]）时钟基因表达节奏在小鼠胚胎成纤维细胞（MEFs）和SCN。此外，自发活动的节奏进行了评估，在年轻和老年mice.ResultsChronic治疗EA和ESTA延迟阶段的PER 2：：LUC的节奏SCN外植体，和ESTA延长期间PER 2：：LUC的节奏在MEFs中的剂量依赖性的方式和增加的幅度PER 2：：LUC的节奏在MEFs中，虽然只有在低浓度。急性治疗与MEFs的PER 2：：LUC节律的影响，取决于浓度和治疗的时间。此外，橡树提取物延长老年小鼠的行为节律的活动时间，并倾向于增加每日轮运行革命在年轻和老年mice.ConclusionsThese结果表明，橡树提取物是一种新的调制器的生物钟在体外和体内。
IntroductionIn mammals, the central circadian clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus, which coordinates the circadian rhythm and controls locomotor activity rhythms. In addition to SCN cells, the peripheral tissues and embryonic fibroblasts also have clock genes, such asPer1/2andBmal1, which generate the transcriptional–translational feedback loop to produce an approximately 24-h cycle. Aging adversely affects the circadian clock system and locomotor functions. Oak extract has been reported to improve age-related physiological changes. However, no study has examined the effect of oak extract on the circadian clock system.MethodsWe examined the effects of oak extract and its metabolites (urolithin A [ULT] and ellagic acid [EA]) on clock gene expression rhythms in mouse embryonic fibroblasts (MEFs) and SCN. Furthermore, locomotor activity rhythm was assessed in young and aged mice.ResultsChronic treatment with EA and ULT delayed the phase of PER2::LUC rhythms in SCN explants, and ULT prolonged the period of PER2::LUC rhythms in MEFs in a dose-dependent manner and increased the amplitude of PER2::LUC rhythms in MEFs, though only at low concentrations. Acute treatment with ULT affected the phase of PER2::LUC rhythms in MEFs depending on the concentration and timing of the treatment. In addition, oak extract prolonged the activity time of behavioral rhythms in old mice and tended to increase daily wheel-running revolutions in both young and old mice.ConclusionsThese results suggest that oak extract is a novel modulator of the circadian clock in vitro and in vivo.