Essential oil and saponin from <i>Semen Platycladi</i> exert sedative-hypnotic effect on ICR mice by regulating multi-targets of serotonergic and GABAergic system

<i>Semen Platycladi</i> (SP) is the dried ripe kernel of <i>Platycladus orientalis</i> (L.) Franco, has been used for insomnia treatment for bimillennium in China, which mechanism is not fully understood. The aim of this study was to explore the sleep-promoting mechanism of essential oil and saponins from SP. As 2 main bioactive constituents of SP, essential oil (SPO) and saponin (SPS) were extracted, then was given to <i>p</i>-chlorophenylalanine (PCPA)-induced insomnia mice by intragastric administration. Then, the behavioral tests, neurotransmitter receptors, cytokines and hormone in brain were investigated. Behavior test showed that SPO and SPS exhibited sleep-enhancing effect through suppressing depression, shortening the onset time while prolonging the sleep duration in insomnia mice. Also SPO and SPS up-regulated serotonin (5-HT) receptors in serotonergic neurons, increased glutamic acid decarboxylase (GAD) content in GABAergic neurons, and stimulated <i>γ</i>-aminobutyric acid (GABA) receptors expression to enhance the synaptic inhibition. Moreover, they could down-regulated the cytokines and rebalanced hormone expressions. Although both SPO and SPS exerted sleep-promoting, they had different focusing targets. SPS had stronger effect on neurotransmitter receptors regulation while SPO had better hormone rebalanced ability. Briefly, SPO and SPS exerted sedative-hypnotic effect in insomnia mice through modulating multi-targets in serotonergic and GABAergic system.