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

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.

Poria cocos ethanol extract and its active constituent, pachymic acid, modulate sleep architectures via activation of GABA(A)-ergic transmission in rats / 동물의과학연구지

Poria cocos is a well-known traditional Chinese traditional medicine (TCM) that grows around roots of pine trees in China, Korea, Japan, and North America. Poria cocos has been used in Asian countries to treat insomnia as either a single herb or part of an herbal formula. In a previous experiment, pachymic acid (PA), an active constituent of Poria cocos ethanol extract (PCE), increased pentobarbital-induced sleeping behaviors. The aim of this experiment was to evaluate whether or not PCE and PA modulate sleep architectures in rats as well as whether or not their effects are mediated through GABA(A)-ergic transmission. PCE and PA were orally administered to individual rats 7 days after surgical implantation of a transmitter, and sleep architectures were recorded by Telemetric Cortical encephalogram (EEG) upon oral administration of test drugs. PCE and PA increased total sleep time and non-rapid eye movement (NREM) sleep as well as reduced numbers of sleep/wake cycles recorded by EEG. Furthermore, PCE increased intracellular chloride levels, GAD65/67 protein levels, and alpha-, beta-, and gamma-subunits of GABA(A) receptors in primary cultured hypothalamic neuronal cells. These data suggest that PCE modulates sleep architectures via activation of GABA(A)-ergic systems. Further, as PA is an active component of PCE, they may have the same pharmacological effects.