Abstract:The effect and mechanism of action of a mixture of sleep-inducing peptides isolated from cow milk and Semen ziziphi spinosae and Bulbus lilii extracts on para-chlorophenylalanine-induced (PCPA-induced) insomnia in rat models were investigated. The sleep-inducing effect of the mixture was evaluated by studying the behavioral changes of the ratsusingopen-field tests. By measuring the levels of neurotransmitters and metabolites in the rat brains, the reaction pathway and sleep-inducing mechanism of the mixture were analyzed. There were significant differences between rats treated with the mixture and those in which insomnia had been induced (p<0.05) but no significant differences between the treatment and control groups (p>0.05). The number of stays in the central zone, the duration of the stays, and the total distances movedby the rats treated with the mixture were 11.00, 15.01 s, and 3309.71 cm, respectively. The concentrations of γ-aminobutyric acid (GABA), glutamic acid (Glu), glycine (Gly), noradrenaline (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) in the brains of the mixture-treated group were 94.96 μg/mL, 1508.42 μg/L, 74.59 μg/L, 37.36 μg/L, 1.76 μg/L, and 1.61 μg/L, respectively. In addition, the mixture-treated rats had significantly higher levels of hypothalamic inhibitory neurotransmitters, namely GABA, than the rats with insomnia (p<0.05) but significantly lower levels of excitatory neurotransmitters, namely NE and DA (p<0.05). The results suggest that the mixture of cow-milk-derived sleep-inducing peptides and Semen ziziphi spinosae and Bulbus lilii extracts can regulate the release of hypothalamic neurotransmittersand improve the behavior and sleep of rat models of insomnia.
