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

We had previously demonstrated that phlorotannins, which are marine polyphenols, enhance sleep in mice via the GABAA-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 exer...

Full description

Bibliographic Details
Main Authors: Minseok Yoon, Jin-Soo Kim, Sangwoo Seo, Kiwon Lee, Min Young Um, Jaekwang Lee, Jonghoon Jung, Suengmok Cho
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-04-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphar.2020.00494/full
_version_ 1828375537473552384
author Minseok Yoon
Jin-Soo Kim
Sangwoo Seo
Kiwon Lee
Kiwon Lee
Min Young Um
Jaekwang Lee
Jonghoon Jung
Suengmok Cho
author_facet Minseok Yoon
Jin-Soo Kim
Sangwoo Seo
Kiwon Lee
Kiwon Lee
Min Young Um
Jaekwang Lee
Jonghoon Jung
Suengmok Cho
author_sort Minseok Yoon
collection DOAJ
description We had previously demonstrated that phlorotannins, which are marine polyphenols, enhance sleep in mice via the GABAA-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 sleep-enhancing 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 GABAA-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 GABAA-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.
first_indexed 2024-04-14T07:48:49Z
format Article
id doaj.art-60e7d75c69a046aabdf83e9f79ce2578
institution Directory Open Access Journal
issn 1663-9812
language English
last_indexed 2024-04-14T07:48:49Z
publishDate 2020-04-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Pharmacology
spelling doaj.art-60e7d75c69a046aabdf83e9f79ce25782022-12-22T02:05:15ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-04-011110.3389/fphar.2020.00494503674Dieckol, a Major Marine Polyphenol, Enhances Non-Rapid Eye Movement Sleep in Mice via the GABAA-Benzodiazepine ReceptorMinseok Yoon0Jin-Soo Kim1Sangwoo Seo2Kiwon Lee3Kiwon Lee4Min Young Um5Jaekwang Lee6Jonghoon Jung7Suengmok Cho8Korea Food Research Institute, Wanju-gun, South KoreaDepartment of Seafood Science and Technology, Institute of Marine Industry, Gyeongsang National University, Tongyeong, South KoreaWCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, South KoreaWCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul, South KoreaAdvanced Institutes of Convergence Technology, Seoul National University, Suwon, South KoreaKorea Food Research Institute, Wanju-gun, South KoreaKorea Food Research Institute, Wanju-gun, South KoreaKorea Food Research Institute, Wanju-gun, South KoreaDepartment of Food Science and Technology/Institute of Food Science, Pukyong National University, Busan, South KoreaWe had previously demonstrated that phlorotannins, which are marine polyphenols, enhance sleep in mice via the GABAA-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 sleep-enhancing 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 GABAA-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 GABAA-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.https://www.frontiersin.org/article/10.3389/fphar.2020.00494/fulldieckolphlorotanninsmarine polyphenolssleepelectroencephalogramhypnotic
spellingShingle Minseok Yoon
Jin-Soo Kim
Sangwoo Seo
Kiwon Lee
Kiwon Lee
Min Young Um
Jaekwang Lee
Jonghoon Jung
Suengmok Cho
Dieckol, a Major Marine Polyphenol, Enhances Non-Rapid Eye Movement Sleep in Mice via the GABAA-Benzodiazepine Receptor
Frontiers in Pharmacology
dieckol
phlorotannins
marine polyphenols
sleep
electroencephalogram
hypnotic
title Dieckol, a Major Marine Polyphenol, Enhances Non-Rapid Eye Movement Sleep in Mice via the GABAA-Benzodiazepine Receptor
title_full Dieckol, a Major Marine Polyphenol, Enhances Non-Rapid Eye Movement Sleep in Mice via the GABAA-Benzodiazepine Receptor
title_fullStr Dieckol, a Major Marine Polyphenol, Enhances Non-Rapid Eye Movement Sleep in Mice via the GABAA-Benzodiazepine Receptor
title_full_unstemmed Dieckol, a Major Marine Polyphenol, Enhances Non-Rapid Eye Movement Sleep in Mice via the GABAA-Benzodiazepine Receptor
title_short Dieckol, a Major Marine Polyphenol, Enhances Non-Rapid Eye Movement Sleep in Mice via the GABAA-Benzodiazepine Receptor
title_sort dieckol a major marine polyphenol enhances non rapid eye movement sleep in mice via the gabaa benzodiazepine receptor
topic dieckol
phlorotannins
marine polyphenols
sleep
electroencephalogram
hypnotic
url https://www.frontiersin.org/article/10.3389/fphar.2020.00494/full
work_keys_str_mv AT minseokyoon dieckolamajormarinepolyphenolenhancesnonrapideyemovementsleepinmiceviathegabaabenzodiazepinereceptor
AT jinsookim dieckolamajormarinepolyphenolenhancesnonrapideyemovementsleepinmiceviathegabaabenzodiazepinereceptor
AT sangwooseo dieckolamajormarinepolyphenolenhancesnonrapideyemovementsleepinmiceviathegabaabenzodiazepinereceptor
AT kiwonlee dieckolamajormarinepolyphenolenhancesnonrapideyemovementsleepinmiceviathegabaabenzodiazepinereceptor
AT kiwonlee dieckolamajormarinepolyphenolenhancesnonrapideyemovementsleepinmiceviathegabaabenzodiazepinereceptor
AT minyoungum dieckolamajormarinepolyphenolenhancesnonrapideyemovementsleepinmiceviathegabaabenzodiazepinereceptor
AT jaekwanglee dieckolamajormarinepolyphenolenhancesnonrapideyemovementsleepinmiceviathegabaabenzodiazepinereceptor
AT jonghoonjung dieckolamajormarinepolyphenolenhancesnonrapideyemovementsleepinmiceviathegabaabenzodiazepinereceptor
AT suengmokcho dieckolamajormarinepolyphenolenhancesnonrapideyemovementsleepinmiceviathegabaabenzodiazepinereceptor