Rosmarinic Acid Potentiates Pentobarbital-Induced Sleep Behaviors and Non-Rapid Eye Movement (NREM) Sleep through the Activation of GABA(A)-ergic Systems.
10.4062/biomolther.2016.035
- Author:
Yeong Ok KWON
1
;
Jin Tae HONG
;
Ki Wan OH
Author Information
1. College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju 28644, Republic of Korea. kiwan@chungbuk.ac.kr
- Publication Type:Original Article
- Keywords:
Rosmarinic acid;
Electroencephalogram;
γ-Aminobutyric acid A receptors subunits;
Glutamic acid decarboxylase;
Pentobarbital-induced sleep;
Insomnia
- MeSH:
Accidental Falls;
Animals;
Electroencephalography;
Eye Movements*;
Glutamate Decarboxylase;
Hand;
Hypnotics and Sedatives;
Medicine, Traditional;
Mice;
Motor Activity;
Pentobarbital;
Perilla frutescens;
Rats;
Receptors, GABA-A;
Rodentia;
Sleep Initiation and Maintenance Disorders;
Sleep, REM
- From:Biomolecules & Therapeutics
2017;25(2):105-111
- CountryRepublic of Korea
- Language:English
-
Abstract:
It has been known that RA, one of major constituents of Perilla frutescens which has been used as a traditional folk remedy for sedation in oriental countries, shows the anxiolytic-like and sedative effects. This study was performed to know whether RA may enhance pentobarbital-induced sleep through γ-aminobutyric acid (GABA)(A)-ergic systems in rodents. RA (0.5, 1.0 and 2.0 mg/kg, p.o.) reduced the locomotor activity in mice. RA decreased sleep latency and increased the total sleep time in pentobarbital (42 mg/kg, i.p.)-induced sleeping mice. RA also increased sleeping time and number of falling sleep mice after treatment with sub-hypnotic pentobarbital (28 mg/kg, i.p.). In electroencephalogram (EEG) recording, RA (2.0 mg/kg) not only decreased the counts of sleep/wake cycles and REM sleep, but also increased the total and NREM sleep in rats. The power density of NREM sleep showed the increase in δ-waves and the decrease in α-waves. On the other hand, RA (0.1, 1.0 and 10 μg/ml) increased intracellular Cl− influx in the primary cultured hypothalamic cells of rats. RA (p.o.) increased the protein expression of glutamic acid decarboxylase (GAD(65/67) ) and GABA(A) receptors subunits except β1 subunit. In conclusion, RA augmented pentobarbital-induced sleeping behaviors through GABA(A)-ergic transmission. Thus, it is suggested that RA may be useful for the treatment of insomnia.
