Marine polyphenol phlorotannins promote non-rapid eye movement sleep in mice via the benzodiazepine site of the GABAA receptor

Title
Marine polyphenol phlorotannins promote non-rapid eye movement sleep in mice via the benzodiazepine site of the GABAA receptor
Authors
Suengmok ChoMinseok Yoon배애님Young-Ho Jin조남철Yohko TakataYoshihiro UradeSojin KimJin-Soo KimHyejin YangJiyoung KimJinkyoung KimJin-Kyu HanMakoto ShimizuZhi-Li Huang
Keywords
GABAA; benzodiazepine; Phlorotannins; GABAA-benzodiazepine receptor; Hypnotic; Marine polyphenols; Sleep promoting
Issue Date
2014-07
Publisher
Psychopharmacology
Citation
VOL 231, NO 14, 2825-2837
Abstract
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.
URI
http://pubs.kist.re.kr/handle/201004/48320
ISSN
00333158
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