Oak extracts modulate circadian rhythms of clock gene expression in vitro and wheel-running activity in mice

Atsushi Haraguchi; Yao Du; Rena Shiraishi; Yuki Takahashi; Takahiro J Nakamura; Shigenobu Shibata

doi:10.1007/s41105-021-00365-2

Oak extracts modulate circadian rhythms of clock gene expression in vitro and wheel-running activity in mice

Sleep Biol Rhythms. 2022 Jan 20;20(2):255-266. doi: 10.1007/s41105-021-00365-2. eCollection 2022 Apr.

Authors

Atsushi Haraguchi¹, Yao Du¹, Rena Shiraishi², Yuki Takahashi², Takahiro J Nakamura², Shigenobu Shibata¹

Affiliations

¹ Department of Electrical Engineering and Bioscience, School of Advanced Science and Engineering, Waseda University, Shinjuku, Tokyo, 162-8480 Japan.
² Laboratory of Animal Physiology, School of Agriculture, Meiji University, Kawasaki, Kanagawa 214-8571 Japan.

Abstract

Introduction: In 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 as Per1/2 and Bmal1, 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.

Methods: We 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.

Results: Chronic 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.

Conclusions: These results suggest that oak extract is a novel modulator of the circadian clock in vitro and in vivo.

Supplementary information: The online version contains supplementary material available at 10.1007/s41105-021-00365-2.

Keywords: Aging; Circadian rhythm; Clock gene; Ellagic acid; Suprachiasmatic nucleus; Urolithin A; Wheel-running activity.