Cho, Suengmok Park, Ji-Hae Pae, Ae Nim Han, Daeseok Kim, Dongsoo Cho, Nam-Chul No, Kyoung Tai Yang, Hyejin Yoon, Minseok Lee, Changho Shimizu, Makoto Baek, Nam-In 2024-01-20T14:33:01Z 2024-01-20T14:33:01Z 2021-09-05 2012-06-01 0968-0896 https://pubs.kist.re.kr/handle/201004/129157 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 gamma-aminobutyric acid type A-benzodiazepine (GABA(A)-BZD) receptor antagonist, similar to other GABA(A)-BZD receptor agonists (e. g., diazepam and zolpidem). The major flavonoid glabrol was isolated from the flavonoid-rich fraction of GGE; it inhibited [H-3] flumazenil binding to the GABA(A)-BZD receptors in rat cerebral cortex membrane with a binding affinity (K-i) of 1.63 mu M. 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 GABA(A)-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 GABA(A)-BZD receptors. (C) 2012 Elsevier Ltd. All rights reserved. English PERGAMON-ELSEVIER SCIENCE LTD GABA(A) RECEPTORS OIL LFO SLEEP PHARMACOLOGY INSOMNIA BINDING ROOTS ACYLTRANSFERASE DIAZEPAM SAFETY Hypnotic effects and GABAergic mechanism of licorice (Glycyrrhiza glabra) ethanol extract and its major flavonoid constituent glabrol Article 10.1016/j.bmc.2012.04.011 1 BIOORGANIC & MEDICINAL CHEMISTRY, v.20, no.11, pp.3493 - 3501 BIOORGANIC & MEDICINAL CHEMISTRY 20 11 3493 3501 scie scopus 000303935800012 2-s2.0-84861196041 Biochemistry & Molecular Biology Chemistry, Medicinal Chemistry, Organic Biochemistry & Molecular Biology Pharmacology & Pharmacy Chemistry Article GABA(A) RECEPTORS OIL LFO SLEEP PHARMACOLOGY INSOMNIA BINDING ROOTS ACYLTRANSFERASE DIAZEPAM SAFETY Glabrol Glycyrrhiza glabra Flavonoid Hypnotic effect GABA type A-benzodiazepine receptor Pharmacophore modeling