Marine polyphenol phlorotannins promote non-rapid eye movement sleep in mice via the benzodiazepine site of the GABAA receptor
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- 作者：Suengmok Cho (1)
Minseok Yoon (1) (2)
Ae Nim Pae (3)
Young-Ho Jin (5)
Nam-Chul Cho (3)
Yohko Takata (4)
Yoshihiro Urade (4)
Sojin Kim (5)
Jin-Soo Kim (2)
Hyejin Yang (1)
Jiyoung Kim (1)
Jinkyoung Kim (6)
Jin-Kyu Han (7)
Makoto Shimizu (8)
Zhi-Li Huang (9) - 关键词：GABAA ; benzodiazepine receptor ; Hypnotic ; Marine polyphenols ; Phlorotannins ; Sleep promoting
- 刊名：Psychopharmacology
- 出版年：2014
- 出版时间：July 2014
- 年：2014
- 卷：231
- 期：14
- 页码：2825-2837
- 全文大小：2,273 KB
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Minseok Yoon (1) (2)
Ae Nim Pae (3)
Young-Ho Jin (5)
Nam-Chul Cho (3)
Yohko Takata (4)
Yoshihiro Urade (4)
Sojin Kim (5)
Jin-Soo Kim (2)
Hyejin Yang (1)
Jiyoung Kim (1)
Jinkyoung Kim (6)
Jin-Kyu Han (7)
Makoto Shimizu (8)
Zhi-Li Huang (9)
1. Korea Food Research Institute, Sungnam, 463-746, Republic of Korea
2. Department of Seafood Science and Technology, Institute of Marine Industry, Gyeongsang National University, Tongyeong, 650-160, Republic of Korea
3. Center for Neuro-Medicine, Korea Institute of Science and Technology, Seoul, 136-791, Republic of Korea
5. Department of Physiology, School of Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea
4. International Institute for Integrative Sleep Medicine, University of Tsukuba, Tsukuba, 305-8575, Japan
6. KGC Lifengin, Seoul, 135-549, Republic of Korea
7. Seoul Sleep Center, Seoul, 135-815, Republic of Korea
8. Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan
9. State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences, Department of Pharmacology, Shanghai Medical College, Fudan University, Shanghai, 200032, China - ISSN：1432-2072
文摘
Rationale In psychopharmacology, researchers have been interested in the hypnotic effects of terrestrial plant polyphenols and their synthetic derivatives. Phlorotannins, a marine plant polyphenol, could have potential as a source of novel hypnotic drugs. Objectives The effects of phlorotannins and major phlorotannin constituent eckstolonol on sleep–wake profiles in mice were evaluated in comparison with diazepam, and their hypnotic mechanism was also investigated. Methods The effects of phlorotannin preparation (PRT) and eckstolonol orally given on sleep–wake profiles were measured by recording electroencephalograms (EEG) and electromyograms in C57BL/6N mice. Flumazenil, a GABAA-benzodiazepine (BZD) receptor antagonist, was injected 15?min before PRT and eckstolonol to reveal its hypnotic mechanism. Results PRT administration (>250?mg/kg) produced a significant decrease in sleep latency and an increase in the amount of non-rapid eye movement sleep (NREMS). Eckstolonol significantly decreased sleep latency (>12.5?mg/kg) and increased the amount of NREMS (50?mg/kg). PRT and eckstolonol had no effect on EEG power density of NREMS. The hypnotic effects of PRT or eckstolonol were completely abolished by pretreatment with flumazenil. Conclusions We demonstrated that phlorotannins promote NREMS by modulating the BZD site of the GABAA receptor. These results suggest that phlorotannins can be potentially used as an herbal medicine for insomnia and as a promising structure for developing novel sedative–hypnotics.