Pachymic Acid Enhances Pentobarbital-Induced Sleeping Behaviors via GABA(A)-ergic Systems in Mice.
- Author:
Vikash Kumar SHAH
1
;
Jae Joon CHOI
;
Jin Yi HAN
;
Mi Kyeong LEE
;
Jin Tae HONG
;
Ki Wan OH
Author Information
1. College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea. kiwan@chungbuk.ac.kr
- Publication Type:Original Article
- Keywords:
Poria cocos (Hoelen);
Pachymic acid (PA);
Insomnia;
Pentobarbital (PENT);
GABA(A) receptors;
Glutamic acid decarboxylase (GAD)
- MeSH:
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
- From:Biomolecules & Therapeutics
2014;22(4):314-320
- CountryRepublic of Korea
- Language:English
-
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.
