Marine polyphenol phlorotannins promote non-rapid eye movement sleep in mice via the benzodiazepine site of the GABAA receptor
- Marine polyphenol phlorotannins promote non-rapid eye movement sleep in mice via the benzodiazepine site of the GABAA receptor
- Suengmok Cho; Minseok Yoon; 배애님; Young-Ho Jin; 조남철; Yohko Takata; Yoshihiro Urade; Sojin Kim; Jin-Soo Kim; Hyejin Yang; Jiyoung Kim; Jinkyoung Kim; Jin-Kyu Han; Makoto Shimizu; Zhi-Li Huang
- GABAA; benzodiazepine; Phlorotannins; GABAA-benzodiazepine receptor; Hypnotic; Marine polyphenols; Sleep promoting
- Issue Date
- VOL 231, NO 14, 2825-2837
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.
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.
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.
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.
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.
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