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


OBJECTIVE
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.
Korea Food Research Institute, Sungnam, 463-746, Republic of Korea.
Suengmok
S
Cho
Minseok
M
Yoon
Ae Nim
AN
Pae
Young-Ho
YH
Jin
Nam-Chul
NC
Cho
Yohko
Y
Takata
Yoshihiro
Y
Urade
Sojin
S
Kim
Jin-Soo
JS
Kim
Hyejin
H
Yang
Jiyoung
J
Kim
Jinkyoung
J
Kim
Jin-Kyu
JK
Han
Makoto
M
Shimizu
Zhi-Li
ZL
Huang
D000818:Animals; D003975:Diazepam / Q000494:pharmacology; D004146:Dioxanes / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005442:Flumazenil / Q000494:pharmacology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000008:administration & dosage / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D059808:Polyphenols / Q000008:administration & dosage / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D012890:Sleep / Q000187:drug effects*; D013634:Tannins / Q000008:administration & dosage / Q000494:pharmacology*
D004146:Dioxanes; D006576:Heterocyclic Compounds, 4 or More Rings; D006993:Hypnotics and Sedatives; D059808:Polyphenols; D011963:Receptors, GABA-A; D013634:Tannins; C507565:eckstolonol; D005442:Flumazenil; D003975:Diazepam