Hypnotic effects and GABAergic mechanism of licorice (Glycyrrhiza glabra) ethanol extract and its major flavonoid constituent glabrol
- Hypnotic effects and GABAergic mechanism of licorice (Glycyrrhiza glabra) ethanol extract and its major flavonoid constituent glabrol
- 조승목; 박지혜; 배애님; 한대석; 김동수; 조남철; 노경태; 양혜진; 윤민석; 이창호; Shimizu, Makoto; 백남인
- Hypnotic effect; pharmacophore; Glabrol; Glycyrrhiza glabra; Flavonoid; GABA type A-benzodiazepine receptor; Pharmacophore modeling
- Issue Date
- Bioorganic & medicinal chemistry
- VOL 20, NO 11, 3493-3501
- Licorice (Glycyrrhiza glabra, GG) is one of the most frequently used herbal medicines worldwide, and its
various biological activities have been widely studied. GG is reported to have neurological properties
such as antidepressant, anxiolytic, and anticonvulsant effects. However, its hypnotic effects and the
mechanism of GG and its active compounds have not yet been demonstrated. In this study, GG ethanol
extract (GGE) dose-dependently potentiated pentobarbital-induced sleep and increased the amount of
non-rapid eye movement sleep in mice without decreasing delta activity. The hypnotic effect of GGE
was completely inhibited by flumazenil, which is a well-known c-aminobutyric acid type A-benzodiazepine
(GABAA-BZD) receptor antagonist, similar to other GABAA-BZD receptor agonists (e.g., diazepam
and zolpidem). The major flavonoid glabrol was isolated from the flavonoid-rich fraction of GGE; it inhibited
[3H] flumazenil binding to the GABAA-BZD receptors in rat cerebral cortex membrane with a binding
affinity (Ki) of 1.63 μM. The molecular structure and pharmacophore model of glabrol and liquiritigenin
indicate that the isoprenyl groups of glabrol may play a key role in binding to GABAA-BZD receptors.
Glabrol increased sleep duration and decreased sleep latency in a dose-dependent manner (5, 10, 25,
and 50 mg/kg); its hypnotic effect was also blocked by flumazenil. The results imply that GGE and its flavonoid
glabrol induce sleep via a positive allosteric modulation of GABAA-BZD receptors.
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