Korean J Physiol Pharmacol.  2017 Jan;21(1):27-36. 10.4196/kjpp.2017.21.1.27.

Potentiation of decursinol angelate on pentobarbital-induced sleeping behaviors via the activation of GABA(A)-ergic systems in rodents

Affiliations
  • 1College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju 28644, Korea. kiwan@chungbuk.ac.kr
  • 2College of Pharmacy, Kyungsung University, Busan, 48434, Korea.

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 GABA(A)-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 (GAD(65/67)) and GABA(A) receptors subtypes. Taken together, these results suggest that DCA potentiates pentobarbital-induced sleeping behaviors through the activation of GABA(A)-ergic systems, and can be useful in the treatment of insomnia.

Keyword

Decursinol angelate; Electroencephalogram; Insomnia; Pentobarbital-induced sleeping; γ-Aminobutyric acid (GABA)A receptors

MeSH Terms

Administration, Oral
Angelica
Animals
Electroencephalography
Eye Movements
Glutamate Decarboxylase
Korea
Medicine, Traditional
Motor Activity
Muscimol
Neurons
Pentobarbital
Rats
Receptors, GABA-A
Rodentia*
Sleep Initiation and Maintenance Disorders
Sleep, REM
Glutamate Decarboxylase
Muscimol
Pentobarbital
Receptors, GABA-A
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