Hypnotic effects and GABAergic mechanism of licorice (Glycyrrhiza glabra) ethanol extract and its major flavonoid constituent glabrol

Title
Hypnotic effects and GABAergic mechanism of licorice (Glycyrrhiza glabra) ethanol extract and its major flavonoid constituent glabrol
Authors
조승목박지혜배애님한대석김동수조남철노경태양혜진윤민석이창호Shimizu, Makoto백남인
Keywords
Hypnotic effect; pharmacophore; Glabrol; Glycyrrhiza glabra; Flavonoid; GABA type A-benzodiazepine receptor; Pharmacophore modeling
Issue Date
2012-06
Publisher
Bioorganic & medicinal chemistry
Citation
VOL 20, NO 11, 3493-3501
Abstract
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.
URI
http://pubs.kist.re.kr/handle/201004/45700
ISSN
09680896
Appears in Collections:
KIST Publication > Article
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