Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Pachymic Acid Enhances Pentobarbital-Induced Sleeping Behaviors via GABAA-ergic Systems in Mice

  • Shah, Vikash Kumar (College of Pharmacy, Chungbuk National University) ;
  • Choi, Jae Joon (College of Pharmacy, Chungbuk National University) ;
  • Han, Jin-Yi (Institute of Veterinary Medicine, Chungbuk National University) ;
  • Lee, Mi Kyeong (College of Pharmacy, Chungbuk National University) ;
  • Hong, Jin Tae (College of Pharmacy, Chungbuk National University) ;
  • Oh, Ki-Wan (College of Pharmacy, Chungbuk National University)
  • Received : 2014.04.21
  • Accepted : 2014.06.13
  • Published : 2014.07.31
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Abstract

This study was investigated to know whether pachymic acid (PA), one of the predominant triterpenoids in Poria cocos (Hoelen) has the sedative-hypnotic effects, and underlying mechanisms are mediated via ${\gamma}$-aminobutyric acid (GABA)-ergic systems. Oral administration of PA markedly suppressed locomotion activity in mice. This compound also prolonged sleeping time, and reduced sleep latency showing synergic effects with muscimol (0.2 mg/kg) in shortening sleep onset and enhancing sleep time induced by pentobarbital, both at the hypnotic (40 mg/kg) and sub-hypnotic (28 mg/kg) doses. Additionally, PA elevated intracellular chloride levels in hypothalamic primary cultured neuronal cells of rats. Moreover, Western blotting quantitative results showed that PA increased the amount of protein level expression of $GAD_{65/67}$ over a broader range of doses. PA increased ${\alpha}$- and ${\beta}$-subunits protein levels, but decreased ${\gamma}$-subunit protein levels in $GABA_A$ receptors. The present experiment provides evidence for the hypnotic effects as PA enhanced pentobarbital-induced sleeping behaviors via $GABA_A$-ergic mechanisms in rodents. Taken together, it is proposed that PA may be useful for the treatment of sleep disturbed subjects with insomnia.

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References

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