Arousal Inhibitory Effect of Phlorotannins on Caffeine in Pentobarbital-Induced Mice

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  • ABSTRACT

    Sleep is vital to maintain health and well-being; however, insomnia is currently a widespread health complaint worldwide. In particular, caffeine, a psychoactive component of coffee, tea, and caffeine beverages may lead to sleep disorders such as insomnia. In this study, our primary objective was to investigate the inhibitory effect of high-purity phlorotannin preparation (HP-PRT) on caffeine-induced wakefulness. The sleep test of pentobarbital-induced mice was used as an in vivo animal model. Caffeine (50 and 100 mg/kg) showed significant arousal effects (an increase in sleep latency and a decrease in sleep duration). Co-administration of caffeine (50 mg/kg) and the sedative-hypnotic diazepam (DZP, 1 mg/kg) did not result in similar arousal activity. HP-PRT (500 mg/kg) also inhibited caffeine-induced wakefulness. Our results suggest that HP-PRT would be a useful additive for developing coffee products without the arousal effect.


  • KEYWORD

    Phlorotannins , Somnogenic , effect , Caffeine , Arousal effect , Pentobarbital-induced sleep test

  • 1. Amos S, Binda L, Chindo BA, Tseja A, Odutola AA, Wambebe C, Gamaniel K 2003 Neuropharmacological effects of Hibiscus sabdariffa aqueous extract [Pharm Biol] Vol.41 P.325-329 google
  • 2. 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
  • 3. 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
  • 4. Brown J, Kreiger N, Darlington GA, Sloan M 2001 Misclassification of exposure: coffee as a surrogate for caffeine intake [Am J Epidemiol] Vol.153 P.815-820 google
  • 5. 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
  • 6. 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
  • 7. Davis JM, Zhao Z, Stock HS, Mehl KA, Buggy J, Hand GA 2003 Central nervous system effects of caffeine and adenosine on fatigue [Am J Physiol Regul Integr Comp Physiol] Vol.284 P.399-404 google
  • 8. De Sousa FCF, Pereira BA, Lima VTM, Lacerda CDG, Melo CTV, Barbosa-Filho JM, Vasconcelos SMM, Viana GSB 2005 Central nervous system activity of yangambin from Ocotea duckei Vattimo (Lauraceae) in mice [Phytother Res] Vol.19 P.282-286 google
  • 9. El Yacoubi M, Ledent C, Parmentier M, Costentin J, Vaugeois JM 2003 Caffeine reduces hypnotic effects of alcohol through adenosine A2A receptor blockade [Neuropharmacology] Vol.45 P.977-985 google
  • 10. Fang XS, Hao JF, Zhou HY, Zhu LX, Wang JH, Song FQ 2010 Pharmacological studies on the sedative-hypnotic effect of Semen Ziziphi spinosae (Suanzaoren) and Radix et Rhizoma Salviae miltiorrhizae (Danshen) extracts and the synergistic effect of their combinations [Phytomedicine] Vol.17 P.75-80 google
  • 11. Gangwisch JE, Malaspina D, Boden-Albala B, Heymsfield SB 2005 Inadequate sleep as a risk factor for obesity: analyses of the NHANES I [Sleep] Vol.28 P.1289-1296 google
  • 12. Gerak LR, Stevenson MW, Winsauer PJ, Moerschbaecher JM 2004 Effects of pregnanolone alone and in combination with other positive GABAA modulators on complex behavior in rats [Psychopharmacology] Vol.173 P.195-202 google
  • 13. Huang ZL, Qu WM, Eguchi N, Chen JF, Schwarzschild MA, Fredholm BB, Urade Y, Hayaishi O 2005 Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine [Nat Neurosci] Vol.8 P.858-859 google
  • 14. Kim AR, Shin TS, Lee MS, Park JY, Park KE, Yoon NY, Kim JS, Choi JS, Jang BC, Byun DS, Park NK, Kim HR 2009 Isolation and identification of phlorotannins from Ecklonia stolonifera with antioxidant and anti-inflammatory properties [J Agric Food Chem] Vol.57 P.3483-3489 google
  • 15. Koob GF 2004 A role for GABA mechanisms in the motivational effects of alcohol [Biochem Pharmacol] Vol.68 P.1515-1525 google
  • 16. Kopp C, Rudolph U, Keist R, Tobler I 2003 Diazepam-induced changes on sleep and the EEG spectrum in mice: role of the α3-GABAA receptor subtype [Eur J Neurosci] Vol.17 P.2226-2230 google
  • 17. Krueger JM, Rector DM, Roy S, Van Dongen HP, Belenky G, Panksepp J 2008 Sleep as a fundamental property of neuronal assemblies [Nat Rev Neurosci] Vol.9 P.910-919 google
  • 18. Kumar S, Porcu P, Werner DF, Matthews DB, Diaz-Granados JL, Helfand RS, Morrow AL 2009 The role of GABAA receptors in the acute and chronic effects of ethanol: a decade of progress [Psychopharmacology] Vol.205 P.529-564 google
  • 19. Lobo IA, Harris RA 2008 GABAA receptors and alcohol [Pharmacol Biochem Behav] Vol.90 P.90-94 google
  • 20. Ma Y, Ma H, Eun JS, Nam SY, Kim YB, Hong JT, Lee MK, Oh KW 2009 Methanol extract of Longanae Arillus augments pentobarbital-induced sleep behaviors through the modification of GABAergic systems [J Ethnopharmacol] Vol.122 P.245-250 google
  • 21. Miller MA, Cappuccio FP 2007 Inflammation, sleep, obesity and cardiovascular disease [Curr Vasc Pharmacol] Vol.5 P.93-102 google
  • 22. Nagayama K, Iwamura Y, Shibata T, Hirayama I, Nakamura T 2002 Bactericidal activity of phlorotannins from the brown alga Ecklonia kurome. [J Antimicrob Chemother] Vol.50 P.889-893 google
  • 23. 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 Behav] Vol.94 P.16-23 google
  • 24. Risa J, Risa A, Adsersen A, Gauguin B, Stafford GI, van Staden J, Jager AK 2004 Screening of plants used in southern Africa for epilepsy and convulsions in the GABAA-benzodiazepine receptor assay [J Ethnopharmacol] Vol.93 P.177-182 google
  • 25. Sanchez-Ortuno M, Moore N, Taillard J, Valtat C, Leger D, Bioulac B, Philip P 2005 Sleep duration and caffeine consumption in a French middle-aged working population [Sleep Med] Vol.6 P.247-251 google
  • 26. Shibata T, Fujimoto K, Nagayama K, Yamaguchi K, Nakayama T 2002 Inhibitory activity of brown algal phlorotannins against hyaluronidase [Int J Food Sci Tech] Vol.37 P.703-709 google
  • 27. Somogyi LP 2010 Caffeine intake by the U.S. population, FDA comments. Subcontract No. 70000073494 P.1-85 google
  • 28. Strassnig M, Brar JS, Ganguli R 2006 Increased caffeine and nicotine consumption in community-dwelling patients with schizophrenia [Schizophr Res] Vol.86 P.269-275 google
  • 29. Sugiura Y, Takeuchi Y, Kakinuma M, Amano H 2006 Inhibitory effects of seaweeds on histamine release from rat basophile leukemia cells (RBL-2H3) [Fisheries Sci] Vol.72 P.1286-1291 google
  • 30. Tobler I, Kopp C, Deboer T, Rudolph U 2001 Diazepam-induced changes in sleep: role of the alpha 1 GABAA receptor subtype [Proc Natl Acad Sci USA] Vol.98 P.6464-6469 google
  • 31. Tuomilehto J, Hu G, Bidel S, Lindstrom J, Jousilahti P 2004 Coffee consumption and risk of type 2 diabetes mellitus among middle-aged Finnish men and women [JAMA] Vol.291 P.1213-1219 google
  • 32. Wolk R, Gami AS, Garcia-Touchard A, Somers VK 2005 Sleep and cardiovascular disease [Curr Probl Cardiol] Vol.30 P.625-662 google
  • 33. Zou Y, Qian ZJ, Li Y, Kim MM, Lee SH, Kim SK 2008 Antioxidant effects of phlorotannins isolated from Ishige okamurae in free radical mediated oxidative systems [J Agric Food Chem] Vol.56 P.7001-7009 google
  • [Fig. 1.] The experimental procedure of the pentobarbital-induced sleep test in mice.
    The experimental procedure of the pentobarbital-induced sleep test in mice.
  • [Fig. 2.] Effects of caffeine on sleep latency (A) and sleep duration (B) in mice administered a hypnotic dose (42 mg/kg, i.p.) of pentobarbital. Mice received pentobarbital 30 min after oral administration (p.o.) of the control group (CON) and caffeine. Each column represents mean ± SEM (n = 10). * p < 0.05, ** p < 0.01, significant difference as compared to the control group (Dunnett’s test).
    Effects of caffeine on sleep latency (A) and sleep duration (B) in mice administered a hypnotic dose (42 mg/kg, i.p.) of pentobarbital. Mice received pentobarbital 30 min after oral administration (p.o.) of the control group (CON) and caffeine. Each column represents mean ± SEM (n = 10). * p < 0.05, ** p < 0.01, significant difference as compared to the control group (Dunnett’s test).
  • [Fig. 3.] Effects of high-purity phlorotannin preparation (HP-PRT) and diazepam (DZP) on sleep latency (A) and sleep duration (B) in mice administered a hypnotic dose (42 mg/kg, i.p.) of pentobarbital. Mice received pentobarbital 30 min after oral administration (p.o.) of samples. Each column represents mean ± SEM (n = 10). ** p < 0.01, significant difference as compared to the control group (Dunnett’s test).
    Effects of high-purity phlorotannin preparation (HP-PRT) and diazepam (DZP) on sleep latency (A) and sleep duration (B) in mice administered a hypnotic dose (42 mg/kg, i.p.) of pentobarbital. Mice received pentobarbital 30 min after oral administration (p.o.) of samples. Each column represents mean ± SEM (n = 10). ** p < 0.01, significant difference as compared to the control group (Dunnett’s test).
  • [Fig. 4.] Effects of co-administration of diazepam (DZP, 1 mg/kg) and caffeine (CF, 50 mg/kg) on sleep latency (A) and sleep duration (B) in mice administered a hypnotic dose (42 mg/kg, i.p.) of pentobarbital. Each column represents mean ± SEM (n = 10). # p < 0.05, ## p < 0.01, significant difference between each group (unpaired Student’s t-test). NS, not significant.
    Effects of co-administration of diazepam (DZP, 1 mg/kg) and caffeine (CF, 50 mg/kg) on sleep latency (A) and sleep duration (B) in mice administered a hypnotic dose (42 mg/kg, i.p.) of pentobarbital. Each column represents mean ± SEM (n = 10). # p < 0.05, ## p < 0.01, significant difference between each group (unpaired Student’s t-test). NS, not significant.
  • [Fig. 5.] Effects of co-administration of high-purity phlorotannin preparation (HP-PRT, 500 mg/kg) and caffeine (CF, 50 mg/kg) on sleep latency (A) and sleep duration (B) in mice administered a hypnotic dose (42 mg/kg, i.p.) of pentobarbital. Each column represents mean ± SEM (n = 10). # p < 0.05, ## p < 0.01, significant difference between each group (unpaired Student’s t-test). NS, not significant.
    Effects of co-administration of high-purity phlorotannin preparation (HP-PRT, 500 mg/kg) and caffeine (CF, 50 mg/kg) on sleep latency (A) and sleep duration (B) in mice administered a hypnotic dose (42 mg/kg, i.p.) of pentobarbital. Each column represents mean ± SEM (n = 10). # p < 0.05, ## p < 0.01, significant difference between each group (unpaired Student’s t-test). NS, not significant.