Sinomenine, an Alkaloid Derived from Sinomenium acutum Potentiates Pentobarbital-Induced Sleep Behaviors and Non-Rapid Eye Movement (NREM) Sleep in Rodents.
10.4062/biomolther.2017.157
- Author:
Jae Hyeon YOO
1
;
Tae Woo HA
;
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:
Sinomenium acutum;
Sinomenine;
Pentobarbital;
GABA(A)-ergic systems;
Electroencephalogram (EEG);
Insomnia
- MeSH:
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
- From:Biomolecules & Therapeutics
2017;25(6):586-592
- CountryRepublic of Korea
- Language:English
-
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.
