Natural Sleep Aids and Polyphenols as Treatments for Insomnia

Cho, Suengmok; Shimizu, Makoto

doi:10.1016/b978-0-12-411462-3.00015-1

Cited by 14 publications

(13 citation statements)

References 80 publications

(63 reference statements)

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“…Glabrol, which is licorice component, has been characterized as a GABA A -BZD receptor ligand that exhibits hypnotic effects (Cho et al, 2012a). Although many studies have been conducted to reveal the hypnotic effects of polyphenols, they have all been limited to terrestrial plants (Cho and Shimizu, 2015). Recently, we reported for the first time that phlorotannins, which are marine polyphenols, enhance sleep in mice via the GABA A -BZD receptor (Cho et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Dieckol, a Major Marine Polyphenol, Enhances Non-Rapid Eye Movement Sleep in Mice via the GABAA-Benzodiazepine Receptor

et al. 2020

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We had previously demonstrated that phlorotannins, which are marine polyphenols, enhance sleep in mice via the GABA A-benzodiazepine (BZD) receptor. Among the constituents of phlorotannin, dieckol is a major marine polyphenol from the brown alga Ecklonia cava. Although phlorotannins are known to exert hypnotic effects, the sleepenhancing effect of dieckol has not yet been determined. We evaluated the effect of dieckol on sleep-wake state of mice by analyzing electroencephalograms (EEGs) and electromyograms. Flumazenil, a GABA A-BZD antagonist, was used to investigate the molecular mechanism underlying the effects of dieckol on sleep. The polygraphic recordings and corresponding hypnograms revealed that dieckol accelerated the initiation of non-rapid eye movement sleep (NREMS); it shortened sleep latency and increased NREMS duration. According to the change in time-course, dieckol showed sleep-enhancing effects by increasing the amount of NREMS and decreasing wakefulness during the same hours. Additionally, sleep quality was evaluated by analyzing the EEG power density, and dieckol was found to not affect sleep intensity while zolpidem was found to reduce it. Finally, we treated mice with zolpidem or dieckol in combination with flumazenil and found the latter to inhibit the sleep-enhancing effect of dieckol and zolpidem, thereby indicating that dieckol exerts sleep-enhancing effects by activating the GABA A-BZD receptor, similar to zolpidem. These results implied that dieckol can be used as a promising herbal sleep aid with minimal side effects, unlike the existing hypnotics.

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Section: Introductionmentioning

confidence: 99%

Dieckol, a Major Marine Polyphenol, Enhances Non-Rapid Eye Movement Sleep in Mice via the GABAA-Benzodiazepine Receptor

et al. 2020

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“…With respect to pharmacological studies on natural sleep aids, terrestrial polyphenols have been considered as important sedative‐hypnotic phytochemicals (Cho & Shimizu, ). Although marine plants have polyphenols, known as phlorotannins, they have not been recognized as potential sources of natural sleep aids, unlike terrestrial plants.…”

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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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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“…For the last two decades, the sedative-hypnotic effects of medicinal plants and their constituents have been extensively investigated [ 6 ]. In particular, polyphenols have been considered as major sedative-hypnotic phytochemicals.…”

Section: Introductionmentioning

confidence: 99%

Triphlorethol A, a Dietary Polyphenol from Seaweed, Decreases Sleep Latency and Increases Non-Rapid Eye Movement Sleep in Mice

Yoon

Cho

2018

Marine Drugs

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In our previous studies, we have demonstrated that marine polyphenol phlorotannins promote sleep through the benzodiazepine site of the gamma-aminobutyric acid type A (GABAA) receptors. In this follow-up study, the sleep-promoting effects of triphlorethol A, one of the major phlorotannin constituents, were investigated. The effect of triphlorethol A on sleep-wake architecture and profiles was evaluated based on electroencephalogram and electromyogram data from C57BL/6N mice and compared with the well-known hypnotic drug zolpidem. Oral administration of triphlorethol A (5, 10, 25, and 50 mg/kg) dose-dependently decreased sleep latency and increased sleep duration during pentobarbital-induced sleep in imprinting control region mice. Triphlorethol A (50 mg/kg) significantly decreased sleep latency and increased the amount of non-rapid eye movement sleep (NREMS) in C57BL/6N mice, without affecting rapid eye movement sleep (REMS). There was no significant difference between the effects of triphlorethol A at 50 mg/kg and zolpidem at 10 mg/kg. Triphlorethol A had no effect on delta activity (0.5–4 Hz) of NREMS, whereas zolpidem significantly decreased it. These results not only support the sleep-promoting effects of marine polyphenol phlorotannins, but also suggest that the marine polyphenol compound triphlorethol A is a promising structure for developing novel sedative hypnotics.

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Natural Sleep Aids and Polyphenols as Treatments for Insomnia

Cited by 14 publications

References 80 publications

Dieckol, a Major Marine Polyphenol, Enhances Non-Rapid Eye Movement Sleep in Mice via the GABAA-Benzodiazepine Receptor

Dieckol, a Major Marine Polyphenol, Enhances Non-Rapid Eye Movement Sleep in Mice via the GABAA-Benzodiazepine Receptor

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

Triphlorethol A, a Dietary Polyphenol from Seaweed, Decreases Sleep Latency and Increases Non-Rapid Eye Movement Sleep in Mice

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