Biomol Ther.  2017 Nov;25(6):586-592. 10.4062/biomolther.2017.157.

Sinomenine, an Alkaloid Derived from Sinomenium acutum Potentiates Pentobarbital-Induced Sleep Behaviors and Non-Rapid Eye Movement (NREM) Sleep in Rodents

• Yoo JH
• Ha TW
• Hong JT
• Oh KW

• KMID: 2395807
• DOI: http://doi.org/10.4062/biomolther.2017.157

Abstract

Sinomenium acutum has been long used in the preparations of traditional medicine in Japan, China and Korea for the treatment of various disorders including rheumatism, fever, pulmonary diseases and mood disorders. Recently, it was reported that Sinomenium acutum, has sedative and anxiolytic effects mediated by GABA-ergic systems. These experiments were performed to investigate whether sinomenine (SIN), an alkaloid derived from Sinomenium acutum enhances pentobarbital-induced sleep via γ-aminobutyric acid (GABA)-ergic systems, and modulates sleep architecture in mice. Oral administration of SIN (40 mg/kg) markedly reduced spontaneous locomotor activity, similar to diazepam (a benzodiazepine agonist) in mice. SIN shortened sleep latency, and increased total sleep time in a dose-dependent manner when co-administrated with pentobarbital (42 mg/kg, i.p.). SIN also increased the number of sleeping mice and total sleep time by concomitant administration with the sub-hypnotic dosage of pentobarbital (28 mg/kg, i.p.). SIN reduced the number of sleep-wake cycles, and increased total sleep time and non-rapid eye movement (NREM) sleep. In addition, SIN also increased chloride influx in the primary cultured hypothalamic neuronal cells. Furthermore, protein overexpression of glutamic acid decarboxylase (GAD(65/67)) and GABA(A) receptor subunits by western blot were found, being activated by SIN. In conclusion, SIN augments pentobarbital-induced sleeping behaviors through GABA(A)-ergic systems, and increased NREM sleep. It could be a candidate for the treatment of insomnia.

Keyword

Sinomenium acutum; Sinomenine; Pentobarbital; GABA(A)-ergic systems; Electroencephalogram (EEG); Insomnia

MeSH Terms

Administration, Oral
Animals
Anti-Anxiety Agents
Benzodiazepines
Blotting, Western
China
Diazepam
Eye Movements*
Fever
Glutamate Decarboxylase
Japan
Korea
Lung Diseases
Medicine, Traditional
Mice
Mood Disorders
Motor Activity
Neurons
Pentobarbital
Receptors, GABA-A
Rheumatic Diseases
Rodentia*
Sinomenium*
Sleep Initiation and Maintenance Disorders
Anti-Anxiety Agents
Benzodiazepines
Diazepam
Glutamate Decarboxylase
Pentobarbital
Receptors, GABA-A