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

Cho, Suengmok; Yang, Hyejin; Jeon, You Jin; Lee, C. Justin; Jin, Young Ho; Baek, Nam In; Kim, Dong-Soo; Kang, Sung Myung; Yoon, Minseok; Yong, Heim; Shimizu, Makoto; Han, Dongil

doi:10.1016/j.foodchem.2011.08.040

Cited by 70 publications

(66 citation statements)

References 45 publications

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“…In our previous study, phlorotannin supplements (250 and 500 mg/kg) significantly increased nonrandom eye movement sleep and decreased sleep latency in C57BL/6 mice (Cho et al, ). The four‐phlorotannin constituents (eckol, eckstolonol, dieckol, and Triphlorethol A) were characterized as ligands to the GABA A ‐BZD receptor (Cho, Yang, et al, ). In addition, the sedative‐hypnotic effects of phlorotannins were completely inhibited by flumazenil, a specific GABA A ‐BZD receptor antagonist (Cho et al, ).…”

Section: Discussionmentioning

confidence: 99%

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Phlorotannin supplement decreases wake after sleep onset in adults with self‐reported sleep disturbance: A randomized, controlled, double‐blind clinical and polysomnographic study

Kim

Han

et al. 2018

Phytotherapy Research

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Our previous study demonstrated that phlorotannin supplement had a sleep-promoting effect in rodents. In the present study, we investigated whether the phlorotannin supplement could improve sleep in subjects with self-reported sleep disturbances. In a randomized, double-blind, placebo-controlled trial, 24 subjects consumed either a placebo or phlorotannin supplement (500 mg/day) for 1 week, 30-60 min prior to bedtime. Sleep parameters were assessed at baseline and at 1 week with sleep questionnaires and polysomnography. At the end of the treatment period, the complete sets of sleep parameters from 20 subjects. Phlorotannin resulted in a significant increase in "Sleep duration" scores compared to the placebo (p = .044), although there were no significant differences on the total PSQI scores. Polysomnography revealed that wakefulness after sleep onset was significantly lower in the phlorotannin group compared to the placebo group (phlorotannin vs. placebo, -25.5 ± 30.5 vs. -1.7 ± 14.9; p = .045) as well as total wake time (phlorotannin vs. placebo, -0.9 ± 3.0 vs. -6.1 ± 6.8; p = .048). Additionally, the respiratory disturbance index during supine rapid eye movement sleep was significantly lower in the phlorotannin group (p = .035). There were no serious adverse effects in either group. Our data suggest that the phlorotannin supplement improved sleep maintenance (WHO ICTRP: KCT0001892).

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Section: Discussionmentioning

confidence: 99%

“…Our previous studies in mice demonstrated for the first time that phlorotannins exhibited sedative‐hypnotic effects through GABA A ‐benzodiazepine (BZD) receptors (Cho, Han, et al, ; ; Cho, Yang, et al, ). As a follow‐up investigation, we evaluated the efficacy and safety of phlorotannins in human subjects.…”

Section: Introductionmentioning

confidence: 99%

Phlorotannin supplement decreases wake after sleep onset in adults with self‐reported sleep disturbance: A randomized, controlled, double‐blind clinical and polysomnographic study

Kim

Han

et al. 2018

Phytotherapy Research

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“…Terrestrial plant polyphenols are based on gallic acids or flavones, whereas phlorotannins are only derived from oligomers and polymers of phloroglucinol (1,3,5-trihydroxybenzene) (Koivikko et al, 2007). Thus far, many phlorotannins, such as dieckol, eckol, triphlorethol A, bieckol, fucol, fucophlorethol, have been identified (Isaza Martínez and Torres Castañeda 2013; Kim et al, 2014;Cho et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

“…However, a validation for the standardization of phlorotannin products has not been reported. Dieckol is generally the most abundant compound in phlorotannin preparations, and is used as an indicator compound (Shibata et al, 2004;Cho et al, 2012;Goo et al, 2010). Therefore, we developed and validated an HPLC method for the determination of dieckol for the commercialization of phlorotannin preparations.…”

Section: Introductionmentioning

confidence: 99%

Method development and validation for dieckol in the standardization of phlorotannin preparations

Kim

Yang

et al. 2016

Fish Aquatic Sci

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Phlorotannins are reported to have diverse biological properties. However, no analytical methods for the standardization of phlorotannin preparations have been reported. Herein, we developed and validated an analytical method for the determination of dieckol in phlorotannin extracts (PRT) using high-performance liquid chromatography (HPLC). The optimum HPLC conditions consisted of a Supelco Discovery C18 column stationary phase, a mobile phase (A: 15 % HPLC grade methanol in deionized water, B: methanol), UV detection at 230 nm, and a flow rate of 0.7 mL/min. The optimized chromatographic conditions were validated and exhibited good specificity and linearity (R 2 > 0.9994-1.0000). The recoveries were in the range of 100.9-102.3 %. The method had good intermediate (%RSD 1.2) and intra-day (%RSD 0.4-1.7) assay precisions. This HPLC method had good accuracy and quality in the determination of dieckol in PRT.

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“…In our previous studies (Cho et al, 2012a;Cho et al, 2012b), we have demonstrated that phlorotannin extracts from the brown alga Ecklonia cava induce sleep via modulation of the benzodiazepine site of the GABA A receptor. In the present study, the effect of phlorotannins on caffeine-induced wakefulness was evaluated using a pentobarbital-induced sleep test in mice.…”

Section: Introductionmentioning

confidence: 98%

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

Cho¹,

Yang²,

Yoon³

et al. 2014

Fisheries and aquatic sciences

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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.

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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

Cited by 70 publications

References 45 publications

Phlorotannin supplement decreases wake after sleep onset in adults with self‐reported sleep disturbance: A randomized, controlled, double‐blind clinical and polysomnographic study

Phlorotannin supplement decreases wake after sleep onset in adults with self‐reported sleep disturbance: A randomized, controlled, double‐blind clinical and polysomnographic study

Method development and validation for dieckol in the standardization of phlorotannin preparations

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

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