Biomol Ther.  2014 Jul;22(4):314-320.

Pachymic Acid Enhances Pentobarbital-Induced Sleeping Behaviors via GABA(A)-ergic Systems in Mice

• Shah VK
• Choi JJ
• Han JY
• Lee MK
• Hong JT
• Oh KW

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 GAD65/67 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.

Keyword

Poria cocos (Hoelen); Pachymic acid (PA); Insomnia; Pentobarbital (PENT); GABA(A) receptors; Glutamic acid decarboxylase (GAD)

MeSH Terms

Administration, Oral
Animals
Blotting, Western
Cocos
gamma-Aminobutyric Acid
Hypnotics and Sedatives
Locomotion
Mice*
Muscimol
Neurons
Pentobarbital
Poria
Rats
Receptors, GABA-A
Rodentia
Sleep Initiation and Maintenance Disorders
Hypnotics and Sedatives
Muscimol
Pentobarbital
Receptors, GABA-A
gamma-Aminobutyric Acid