Sleep-Promoting Effect of Ecklonia cava: Ethanol Extract Promotes Non-rapid Eye Movement Sleep in C57BL/6N Mice

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  • ABSTRACT

    We investigated the effects of Ecklonia cava ethanol extract (ECE) on sleep architecture and sleep profiles. ECE was orally administered at a dose of 100, 250, or 500 mg/kg to C57BL/6N mice and its effects were measured by recording electroencephalogram (EEG) and electromyogram. Administration of ECE (250 and 500 mg/kg) significantly induced non-rapid eye movement sleep (NREMS) without affecting rapid eye movement sleep. The increase in NREMS by ECE (500 mg/kg) was significant (P < 0.05) during the first 2 h after administration. In addition, ECE had no effect on EEG power density (an indicator of sleep quality) in NREMS. These results suggest that ECE induces NREMS in a manner similar to physiological sleep.


  • KEYWORD

    Ecklonia cava , Electroencephalogram , Electromyogram , Non-rapid eye movement sleep , Delta power

  • 1. Ahn G, Hwang I, Park E, Kim J, Jeon YJ, Lee J, Park JW, Jee Y 2008 Immunomodulatory effects of an enzymatic extract from Ecklonia cava on murine splenocytes [Mar Biotechnol] Vol.10 P.278-289 google
  • 2. Ahn G, Park E, Lee WW, Hyun JW, Lee KW, Shin T, Jeon YJ, Jee Y 2011 Enzymatic extract from Ecklonia cava induces the activation of lymphocytes by IL-2 production through the classical NF-κB pathway [Mar Biotechnol] Vol.13 P.66-73 google
  • 3. Bastien CH, LeBlanc M, Carrier J, Morin CM 2003 Sleep EEG power spectra, insomnia, and chronic use of benzodiazepines [Sleep] Vol.26 P.313-317 google
  • 4. Borja NL, Daniel KL 2006 Ramelteon for the treatment of insomnia [Clin Ther] Vol.28 P.1540-1555 google
  • 5. Brand S, Kirov R 2011 Sleep and its importance in adolescence and in common adolescent somatic and psychiatric conditions [Int J Gen Med] Vol.4 P.425-442 google
  • 6. Cho S, Han D, Kim SB, Yoon M, Yang H, Jin YH, Jo J, Yong H, Lee SH, Jeon YJ, Shimizu M 2012 Depressive effects on the central nervous system and underlying mechanism of the enzymatic extract and its phlorotannin-rich fraction from Ecklonia cava edible brown seaweed [Biosci Biotechnol Biochem] Vol.76 P.163-168 google
  • 7. Cho S, Yang H, Jeon YJ, Lee CJ, Jin YH, Baek NI, Kim D, Kang SM, Yoon M, Yong H, Shimizu M, Han D 2012 Phlorotannins of the edible brown seaweed Ecklonia cava Kjellman induce sleep via positive allosteric modulation of gamma-aminobutyric acid type A-benzodiazepine receptor: a novel neurological activity of seaweed polyphenols [Food Chem] Vol.132 P.1133-1142 google
  • 8. Cochran WT, Cooley JW, Favin DL, Helms HD, Kaenel RA, Lang WW, Maling GC Jr, Nelson DE, Rader CM, Welch PD 1967 What is the fast Fourier transform? [Proc IEEE Inst Electr Electron Eng] Vol.55 P.1664-1674 google
  • 9. Coenen AM, van Luijtelaar EL 1991 Pharmacological dissociation of EEG and behavior: a basic problem in sleep-wake classification [Sleep] Vol.14 P.464-465 google
  • 10. Doghramji K 2006 The epidemiology and diagnosis of insomnia [Am J Manag Care] Vol.12 P.S214-S220 google
  • 11. Erman MK 2008 New perspectives in the diagnosis and management of insomnia [CNS Spectr] Vol.13 P.3 google
  • 12. Heo SJ, Park EJ, Lee KW, Jeon YJ 2005 Antioxidant activities of enzymatic extracts from brown seaweeds [Bioresource Technol] Vol.96 P.1613-1623 google
  • 13. Huber R, Deboer T, Tobler I 2000 Effects of sleep deprivation on sleep and sleep EEG in three mouse strains: empirical data and simulations [Brain Res] Vol.857 P.8-19 google
  • 14. Imeri L, Opp MR 2009 How (and why) the immune system makes us sleep [Nat Rev Neurosci] Vol.10 P.199-210 google
  • 15. Ishida T, Obara Y, Kamei C 2009 Effects of some antipsychotics and a benzodiazepine hypnotic on the sleep-wake pattern in an animal model of schizophrenia [J Pharmacol Sci] Vol.111 P.44-52 google
  • 16. Kim MM, Kim SK 2010 Effect of phloroglucinol on oxidative stress and inflammation [Food Chem Toxicol] Vol.48 P.2925-2933 google
  • 17. Kim TH, Bae JS 2010 Ecklonia cava extracts inhibit lipopolysaccharide induced inflammatory responses in human endothelial cells [Food Chem Toxicol] Vol.48 P.1682-1687 google
  • 18. Kohtoh S, Taguchi Y, Matsumoto N, Wada M, Huang ZL, Urade Y 2008 Algorithm for sleep scoring in experimental animals based on fast Fourier transform power spectrum analysis of the electroencephalogram [Sleep Biol Rhythms] Vol.6 P.163-171 google
  • 19. Kong CS, Kim JA, Yoon NY, Kim SK 2009 Induction of apoptosis by phloroglucinol derivative from Ecklonia cava in MCF-7 human breast cancer cells [Food Chem Toxicol] Vol.47 P.1653-1658 google
  • 20. Krueger JM, Rector DM, Roy S, Van Dongen HPA, Belenky G, Panksepp J 2008 Sleep as a fundamental property of neuronal assemblies [Nat Rev Neurosci] Vol.9 P.910-919 google
  • 21. Le QT, Li Y, Qian ZJ, Kim MM, Kim SK 2009 Inhibitory effects of polyphenols isolated from marine alga Ecklonia cava on histamine release [Process Biochem] Vol.44 P.168-176 google
  • 22. Lee H, Kang C, Jung ES, Kim JS, Kim E 2011 Antimetastatic activity of polyphenol-rich extract of Ecklonia cava through the inhibition of the Akt pathway in A549 human lung cancer cells [Food Chem] Vol.127 P.1229-1236 google
  • 23. Li Y, Qian ZJ, Ryu BM, Lee SH, Kim MM, Kim SK 2009 Chemical components and its antioxidant properties in vitro: an edible marine brown alga, Ecklonia cava [Bioorg Med Chem] Vol.17 P.1963-1973 google
  • 24. Masaki M, Aritake K, Tanaka H, Shoyama Y, Huang ZL, Urade Y 2012 Crocin promotes non-rapid eye movement sleep in mice [Mol Nutr Food Res] Vol.56 P.304-308 google
  • 25. Meletis CD, Zabriskie N 2008 Natural approaches for optimal sleep [Alternat Complement Ther] Vol.14 P.181-188 google
  • 26. Qiu MH, Qu WM, Xu XH, Yan MM, Urade Y, Huang ZL 2009 D1/D2 receptor-targeting L-stepholidine, an active ingredient of the Chinese herb Stephonia, induces non-rapid eye movement sleep in mice [Pharmacol Biochem Be] Vol.94 P.16-23 google
  • 27. Qu WM, Xu XH, Yan MM, Wang YQ, Urade Y, Huang ZL 2010 Essential role of dopamine D2 receptor in the maintenance of wakefulness, but not in homeostatic regulation of sleep, in mice [J Neurosci] Vol.30 P.4382-4389 google
  • 28. Shim SY, Quang-To L, Lee SH, Kim SK 2009 Ecklonia cava extract suppresses the high-affinity IgE receptor, FcεRI expression [Food Chem Toxicol] Vol.47 P.555-560 google
  • 29. Tobler I, Kopp C, Deboer T, Rudolph U 2001 Diazepam-induced changes in sleep: Role of the α1 GABAA receptor subtype [Proc Natl Acad Sci USA] Vol.98 P.6464-6469 google
  • 30. van Lier H, Drinkenburg WH, van Eeten YJ, Coenen AM 2004 Effects of diazepam and zolpidem on EEG beta frequencies are behavior-specific in rats [Neuropharmacology] Vol.47 P.163-174 google
  • 31. Winsky-Sommerer R 2009 Role of GABAA receptors in the physiology and pharmacology of sleep [Eur J Neurosci] Vol.29 P.1779-1794 google
  • [Fig. 1.] Surgery for EEG and EMG recordings (A). An inside view of the recording chamber (B). Typical EEG, EMG and FFT spectra in mice (C). The EEG and EMG signals and FFT spectra were collected from a vehicle control mouse in this study. EEG, electroencephalogram; EMG, electromyogram; FFT, fast Fourier transform; NREMS, non-rapid eye movement sleep; REMS, rapid eye movement sleep; Wake, wakefulness.
    Surgery for EEG and EMG recordings (A). An inside view of the recording chamber (B). Typical EEG, EMG and FFT spectra in mice (C). The EEG and EMG signals and FFT spectra were collected from a vehicle control mouse in this study. EEG, electroencephalogram; EMG, electromyogram; FFT, fast Fourier transform; NREMS, non-rapid eye movement sleep; REMS, rapid eye movement sleep; Wake, wakefulness.
  • [Fig. 2.] (A) Representative examples of EEG and EMG signals and corresponding hypnograms in a mouse treated with vehicle, ECE, and DZP. (B) Effects of ECE and DZP on sleep latency. (C) Total time spent in NREMS and REMS for 3 h after administration. Each column represents the mean ± SEM (n = 8). **P < 0.01, compared with vehicle (unpaired Student’s t-test). ##P < 0.01, significant as compared with ECE (100 mg/kg; Dunnett’s test). DZP, diazepam; ECE, Ecklonia cava ethanol extract; EEG, electroencephalogram; EMG, electromyogram; NREMS (or NR), non-rapid eye movement sleep; NS, not significant; REMS (or R), rapid eye movement sleep; Wake (or W), wakefulness.
    (A) Representative examples of EEG and EMG signals and corresponding hypnograms in a mouse treated with vehicle, ECE, and DZP. (B) Effects of ECE and DZP on sleep latency. (C) Total time spent in NREMS and REMS for 3 h after administration. Each column represents the mean ± SEM (n = 8). **P < 0.01, compared with vehicle (unpaired Student’s t-test). ##P < 0.01, significant as compared with ECE (100 mg/kg; Dunnett’s test). DZP, diazepam; ECE, Ecklonia cava ethanol extract; EEG, electroencephalogram; EMG, electromyogram; NREMS (or NR), non-rapid eye movement sleep; NS, not significant; REMS (or R), rapid eye movement sleep; Wake (or W), wakefulness.
  • [Fig. 3.] Time courses of NREMS, REMS, and Wake after the administration of ECE (A) and DZP (B). Each circle represents the hourly mean ± SEM (n = 8) of NREMS, REMS, and Wake. *P < 0.05, **P < 0.01, compared with vehicle (unpaired Student’s t-test). DZP, diazepam; ECE, Ecklonia cava ethanol extract; NREMS, non-rapid eye movement sleep; REMS, rapid eye movement sleep; Wake, wakefulness.
    Time courses of NREMS, REMS, and Wake after the administration of ECE (A) and DZP (B). Each circle represents the hourly mean ± SEM (n = 8) of NREMS, REMS, and Wake. *P < 0.05, **P < 0.01, compared with vehicle (unpaired Student’s t-test). DZP, diazepam; ECE, Ecklonia cava ethanol extract; NREMS, non-rapid eye movement sleep; REMS, rapid eye movement sleep; Wake, wakefulness.
  • [Fig. 4.] Effects of ECE and DZP on changes in the mean duration of each sleep stage (A, B) and EEG power density in NREMS (C, D). Delta activity in NREMS, an index of sleep intensity, is shown in the inset histogram of (C) and (D). The bar (?) represents the range of the delta wave (0.5?4 Hz). *P < 0.05, compared with vehicle (unpaired Student’s t-test). DZP, diazepam; ECE, Ecklonia cava ethanol extract; EEG, electroencephalogram; NREMS, non-rapid eye movement sleep; REMS, rapid eye movement sleep; Wake, wakefulness.
    Effects of ECE and DZP on changes in the mean duration of each sleep stage (A, B) and EEG power density in NREMS (C, D). Delta activity in NREMS, an index of sleep intensity, is shown in the inset histogram of (C) and (D). The bar (?) represents the range of the delta wave (0.5?4 Hz). *P < 0.05, compared with vehicle (unpaired Student’s t-test). DZP, diazepam; ECE, Ecklonia cava ethanol extract; EEG, electroencephalogram; NREMS, non-rapid eye movement sleep; REMS, rapid eye movement sleep; Wake, wakefulness.