Hypnotic effect of jujubosides from Semen Ziziphi Spinosae

Semen Ziziphi Spinosae, the seed of Ziziphus jujuba Mill. var. spinosa (bunge) Hu ex H.F. Chow has been widely used in treating insomnia and anxiety. In this study, we investigated the hypnotic effect of jujubosides, one of the major components (saponin) of Semen Ziziphi Spinosae, in both day and night period. After the administration of jujubosides (9 mg/kg once per day for 3 days), sleep parameters were examined by EEG and EMG analysis in normal rats and the action of jujubosides on pentobarbital-induced sleep assessed by the loss-of righting reflex. During daytime (9:00–15:00), jujubosides significantly increased the total sleep and rapid eye movement (REM) sleep without significant influence on non-REM (NREM) sleep. During nighttime (21:00–3:00), jujubosides significantly increased the total sleep and NREM sleep especially the light sleep while showed no significant effect on REM sleep and slow wave sleep (SWS). In pentobarbital-treated mice, jujubosides significantly augmented the hypnotic effect of pentobarbital (45 mg/kg, i.p.), proved by increasing sleep time and this augmentative effect was potentiated by 5-hydroxytryptophan (2 mg/kg, i.p.). Furthermore, jujubosides inhibited the para-chlorophenylalanine-induced suppression of pentobarbital-induced hypnosis. These results suggested that the hypnotic effect of jujubosides on normal rats may be influenced by circadian rhythm and the serotonergic system may involve in the hypnotic effect of jujubosides. Jujubosides may be good source of lead compounds for novel hypnotics.