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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)255-266
Number of pages12
JournalSleep and Biological Rhythms
Issue number2
Publication statusPublished - 2022 Apr


  • Aging
  • Circadian rhythm
  • Clock gene
  • Ellagic acid
  • Suprachiasmatic nucleus
  • Urolithin A
  • Wheel-running activity

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Neurology
  • Physiology (medical)
  • Physiology


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