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

Semen Platycladi (SP) is the dried ripe kernel of Platycladus orientalis (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 p-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 γ-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.