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...
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Frontiers Media S.A.
2020-04-01
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Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00494/full |
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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. |
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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 |
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