Biomolecules & Therapeutics  2017;25(2):105-111

doi:10.4062/biomolther.2016.035

Rosmarinic Acid Potentiates Pentobarbital-Induced Sleep Behaviors and Non-Rapid Eye Movement (NREM) Sleep through the Activation of GABA(A)-ergic Systems.

Yeong Ok KWON 1 ; Jin Tae HONG ; Ki Wan OH

Affiliations

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Keywords

Rosmarinic acid; Electroencephalogram; γ-Aminobutyric acid A receptors subunits; Glutamic acid decarboxylase; Pentobarbital-induced sleep; Insomnia

Country

Republic 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.