Psychopharmacology

, Volume 231, Issue 14, pp 2825–2837 | Cite as

Marine polyphenol phlorotannins promote non-rapid eye movement sleep in mice via the benzodiazepine site of the GABAA receptor

  • Suengmok Cho
  • Minseok Yoon
  • Ae Nim Pae
  • Young-Ho Jin
  • Nam-Chul Cho
  • Yohko Takata
  • Yoshihiro Urade
  • Sojin Kim
  • Jin-Soo Kim
  • Hyejin Yang
  • Jiyoung Kim
  • Jinkyoung Kim
  • Jin-Kyu Han
  • Makoto Shimizu
  • Zhi-Li Huang
Original Investigation

Abstract

Rationale

In psychopharmacology, researchers have been interested in the hypnotic effects of terrestrial plant polyphenols and their synthetic derivatives. Phlorotannins, a marine plant polyphenol, could have potential as a source of novel hypnotic drugs.

Objectives

The effects of phlorotannins and major phlorotannin constituent eckstolonol on sleep–wake profiles in mice were evaluated in comparison with diazepam, and their hypnotic mechanism was also investigated.

Methods

The effects of phlorotannin preparation (PRT) and eckstolonol orally given on sleep–wake profiles were measured by recording electroencephalograms (EEG) and electromyograms in C57BL/6N mice. Flumazenil, a GABAA-benzodiazepine (BZD) receptor antagonist, was injected 15 min before PRT and eckstolonol to reveal its hypnotic mechanism.

Results

PRT administration (>250 mg/kg) produced a significant decrease in sleep latency and an increase in the amount of non-rapid eye movement sleep (NREMS). Eckstolonol significantly decreased sleep latency (>12.5 mg/kg) and increased the amount of NREMS (50 mg/kg). PRT and eckstolonol had no effect on EEG power density of NREMS. The hypnotic effects of PRT or eckstolonol were completely abolished by pretreatment with flumazenil.

Conclusions

We demonstrated that phlorotannins promote NREMS by modulating the BZD site of the GABAA receptor. These results suggest that phlorotannins can be potentially used as an herbal medicine for insomnia and as a promising structure for developing novel sedative–hypnotics.

Keywords

GABAA-benzodiazepine receptor Hypnotic Marine polyphenols Phlorotannins Sleep promoting 

Notes

Acknowledgments

This study was supported by grants from the Korea Food Research Institute (E0131402), Small and Medium Business Administration (G01981), the National Basic Research Program of China (2011CB711000, 2009ZX09303-006), the National Natural Science Foundation of China (31171010, 31121061, 31271164), the Shanghai Committee of Science and Technology (13140903100, 13dz2260700), and the Shanghai Leading Academic Discipline Project (B119).

Conflict of interest

All authors declare no conflicts of interest and had no disclosures.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Suengmok Cho
    • 1
  • Minseok Yoon
    • 1
    • 2
  • Ae Nim Pae
    • 3
  • Young-Ho Jin
    • 5
  • Nam-Chul Cho
    • 3
  • Yohko Takata
    • 4
  • Yoshihiro Urade
    • 4
  • Sojin Kim
    • 5
  • Jin-Soo Kim
    • 2
  • Hyejin Yang
    • 1
  • Jiyoung Kim
    • 1
  • Jinkyoung Kim
    • 6
  • Jin-Kyu Han
    • 7
  • Makoto Shimizu
    • 8
  • Zhi-Li Huang
    • 9
  1. 1.Korea Food Research InstituteSungnamRepublic of Korea
  2. 2.Department of Seafood Science and Technology, Institute of Marine IndustryGyeongsang National UniversityTongyeongRepublic of Korea
  3. 3.Center for Neuro-MedicineKorea Institute of Science and TechnologySeoulRepublic of Korea
  4. 4.International Institute for Integrative Sleep MedicineUniversity of TsukubaTsukubaJapan
  5. 5.Department of Physiology, School of MedicineKyung Hee UniversitySeoulRepublic of Korea
  6. 6.KGC LifenginSeoulRepublic of Korea
  7. 7.Seoul Sleep CenterSeoulRepublic of Korea
  8. 8.Graduate School of Agricultural and Life SciencesThe University of TokyoTokyoJapan
  9. 9.State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences, Department of Pharmacology, Shanghai Medical CollegeFudan UniversityShanghaiChina

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