title: Potentiation of decursinol angelate on pentobarbital-induced sleeping behaviorsviathe activation of GABAA-ergic systems in rodents.
abstract: Angelicae Gigantis Radix (AGR,Angelica gigas) has been used for a long time as a traditional folk medicine in Korea and oriental countries. Decursinol angelate (DCA) is structurally isomeric decursin, one of the major components of AGR. This study was performed to confirm whether DCA augments pentobarbital-induced sleeping behaviors via the activation of GABAA-ergic systems in animals. Oral administration of DCA (10, 25 and 50 mg/kg) markedly suppressed spontaneous locomotor activity. DCA also prolonged sleeping time, and decreased the sleep latency by pentobarbital (42 mg/kg), in a dose-dependent manner, similar to muscimol, both at the hypnotic (42 mg/kg) and sub-hypnotic (28 mg/kg) dosages. Especially, DCA increased the number of sleeping animals in the sub-hypnotic dosage. DCA (50 mg/kg, p.o.) itself modulated sleep architectures; DCA reduced the counts of sleep/wake cycles. At the same time, DCA increased total sleep time, but not non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. In the molecular experiments. DCA (0.001, 0.01 and 0.1 µg/ml) increased intracellular Cl- influx level in hypothalamic primary cultured neuronal cells of rats. In addition, DCA increased the protein expression of glutamic acid decarboxylase (GAD65/67) and GABAAreceptors subtypes. Taken together, these results suggest that DCA potentiates pentobarbital-induced sleeping behaviors through the activation of GABAA-ergic systems, and can be useful in the treatment of insomnia.
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju 28644, Korea.
authors.forename: Jae Hoon
authors.initials: JH
authors.lastname: Woo
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju 28644, Korea.
authors.forename: Tae-Woo
authors.initials: TW
authors.lastname: Ha
authors.affiliation: College of Pharmacy, Kyungsung University, Busan, 48434, Korea.
authors.forename: Jae-Seon
authors.initials: JS
authors.lastname: Kang
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju 28644, Korea.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.affiliation: College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju 28644, Korea.
authors.forename: Ki-Wan
authors.initials: KW
authors.lastname: Oh
keywords: Decursinol angelate; Electroencephalogram; Insomnia; Pentobarbital-induced sleeping; γ-Aminobutyric acid (GABA)A receptors