Potentiation of decursinol angelate on pentobarbital-induced sleeping behaviorsviathe activation of GABA_A-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 GABAA receptors 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.

A Sargassum fluitans Borgesen Ethanol Extract Exhibits a Hepatoprotective Effect In Vivo in Acute and Chronic Liver Damage Models

“…Liver functionality was evaluated with the sleep induction test. Pentobarbital (20 mg/kg) was intraperitoneally injected and sleeping time measured; maximum measured elapsed time was 60 min [16, 17]. Time was recorded at injection and when the rat could no longer accomplish the righting reflex (i.e., the ability to right itself), it was then placed on its back in a standard cage, and time was recorded again when the righting reflex was regained.…”

Sleep-Aids Derived from Natural Products

“…On the other hand, decurcinol potentiates pentobarbital-induced sleeping behaviors through the activation of GABA A -ergic systems. Altogether suggest that decurcinol, can be useful agent for the treatment of insomnia ( Woo et al ., 2017 ).…”

Decursinol-mediated antinociception and anti-allodynia in acute and neuropathic pain models in male mice: Tolerance and receptor profiling

“…CB 1 -induced hypothermia has been reported to occur via CB 1 -stimulated GABA release in the hypothalamus ( Rawls et al, 2004 ). Likewise, administration of the decursinol precursor decursinol angelate has been shown to potentiate pentobarbital-induced sleeping behaviors through the activation of the GABA A -ergic systems ( Woo et al, 2017 ). Therefore, it is possible that CB 1 receptors play a role in modulating decursinol-induced hypothermia, possibly through GABA A activation.…”