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

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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.

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Acknowledgements

This work was supported by JSPS KAKENHI [grant number 17H04022 (T.J.N.)]. We would like to thank Editage (www.editage.com) for English language editing.

Funding

Japan Society for the Promotion of Science, 17H04022, Takahiro Nakamura.

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Authors and Affiliations

  1. Department of Electrical Engineering and Bioscience, School of Advanced Science and Engineering, Waseda University, Shinjuku, Tokyo, 162-8480, Japan

    Atsushi Haraguchi, Yao Du & Shigenobu Shibata

  2. Laboratory of Animal Physiology, School of Agriculture, Meiji University, Kawasaki, Kanagawa, 214-8571, Japan

    Rena Shiraishi, Yuki Takahashi & Takahiro J. Nakamura

Authors
  1. Atsushi Haraguchi
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  2. Yao Du
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  3. Rena Shiraishi
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  4. Yuki Takahashi
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  5. Takahiro J. Nakamura
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  6. Shigenobu Shibata
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Contributions

AH, TJN, and SS conceived and designed the study; AH, YD, RS, YT, and TJN performed the experiments; AH, YD, RS, YT, and TJN analyzed the data; AH, TJN, and SS wrote the manuscript.

Corresponding authors

Correspondence to Takahiro J. Nakamura or Shigenobu Shibata.

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The authors declare that they have no conflicts of interest concerning this article.

Ethical approval

Appropriate approvals for the use of animals in the described experiments have been obtained from the Institutional Animal Care and Use Committee at the School of Agriculture, Meiji University (approval number: IACUC16-0012).

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Haraguchi, A., Du, Y., Shiraishi, R. et al. Oak extracts modulate circadian rhythms of clock gene expression in vitro and wheel-running activity in mice. Sleep Biol. Rhythms 20, 255–266 (2022). https://doi.org/10.1007/s41105-021-00365-2

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  • DOI: https://doi.org/10.1007/s41105-021-00365-2

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