Pachymic Acid Enhances Pentobarbital-Induced Sleeping Behaviors via GABAA-ergic Systems in Mice

Vikash Kumar Shah, Jae Joon Choi, Jin-Yi Han, Mi Kyeong Lee, Jin Tae Hong, and Ki-Wan Oh,

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 γ-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 GAD65/67over a broader range of doses. PA increased α- and β-subunits protein levels, but decreased γ-subunit protein levels in GABAA receptors. The present experiment provides evidence for the hypnotic effects as PA enhanced pentobarbital-induced sleeping behaviors via GABAA

 Pachymic acid (Fig. 1, purity HPLC,98%) was purchased from Chengdu Biopurify Phytochemicals Ltd. (Chengdu, Sichuan, China).