title: Pachymic Acid Enhances Pentobarbital-Induced Sleeping Behaviors via GABAA-ergic Systems in Mice.
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 GAD65/67 over 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-ergic mechanisms in rodents. Taken together, it is proposed that PA may be useful for the treatment of sleep disturbed subjects with insomnia.
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Vikash Kumar
authors.initials: VK
authors.lastname: Shah
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Jae Joon
authors.initials: JJ
authors.lastname: Choi
authors.affiliation: Institute of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Jin-Yi
authors.initials: JY
authors.lastname: Han
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Mi Kyeong
authors.initials: MK
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Ki-Wan
authors.initials: KW
authors.lastname: Oh
keywords: GABAA receptors; Glutamic acid decarboxylase (GAD); Insomnia; Pachymic acid (PA); Pentobarbital (PENT); Poria cocos (Hoelen)