title: Isoliquiritigenin, a chalcone compound, is a positive allosteric modulator of GABAA receptors and shows hypnotic effects.
abstract: Isoliquiritigenin (ILTG) is a chalcone compound and has valuable pharmacological properties such as antioxidant, anti-inflammatory, anticancer, and antiallergic activities. Recently, the anxiolytic effect of ILTG has been reported; however, its action mechanism and hypnotic activity have not yet been demonstrated. Therefore, we investigated the hypnotic effect and action mechanism of ILTG. ILTG significantly potentiated the pentobarbital-induced sleep in mice at doses of 25 and 50mg/kg. The hypnotic activity of ILTG was fully inhibited by flumazenil (FLU), a specific gamma-aminobutyric acid type A (GABA(A))-benzodiazepine (BZD) receptor antagonist. The binding affinity of ILTG was 0.453 μM and was found to be higher than that of the reference compound, diazepam (DZP, 0.012 μM). ILTG (10(-5)M) potentiated GABA-evoked currents to 151% of the control level on isolated dorsal raphe neurons. ILTG has 65 times higher affinity for GABA(A)-BZD receptors than DZP, and the dissociation constant for ILTG was 4.0 × 10(-10)M. The effect of ILTG on GABA currents was blocked by 10(-7)M FLU and ZK-93426. These results suggest that ILTG produces hypnotic effects by positive allosteric modulation of GABA(A)-BZD receptors.
authors.affiliation: Korea Food Research Institute, Seongnam 463-746, Republic of Korea.
authors.forename: Suengmok
authors.initials: S
authors.lastname: Cho
authors.forename: Sojin
authors.initials: S
authors.lastname: Kim
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Jin
authors.forename: Hyejin
authors.initials: H
authors.lastname: Yang
authors.forename: Daeseok
authors.initials: D
authors.lastname: Han
authors.forename: Nam-In
authors.initials: NI
authors.lastname: Baek
authors.forename: Jinho
authors.initials: J
authors.lastname: Jo
authors.forename: Chang-Won
authors.initials: CW
authors.lastname: Cho
authors.forename: Ji-Hae
authors.initials: JH
authors.lastname: Park
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimizu
authors.forename: Young-Ho
authors.initials: YH
authors.lastname: Jin
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology; D002478:Cells, Cultured; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology*; D018757:GABA Modulators / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000187:drug effects; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000737:chemistry / Q000378:metabolism*
chemical_list: D047188:Chalcones; D018757:GABA Modulators; D006993:Hypnotics and Sedatives; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C040920:isoliquiritigenin; D010634:Phenobarbital