Rice bran component ?-oryzanol promotes sleep in mice by antagonism of histamine H1 receptor

?-Oryzanol, a unique component of rice bran, has been shown to exert anti-anxiety and anti-depressive effects. Evidence suggests that ?-oryzanol may affect sleep; however, sedative-hypnotic effects have not been reported. In this study, a pentobarbital-induced sleep test and sleep-wake profile assessment using recorded electroencephalography are used. Also, the molecular mechanism of ?-oryzanol's sleep effects is evaluated in histamine H-1 receptor (H1R)-knockout (KO) mice. ?-Oryzanol gave a dose-dependent reduction in sleep latency and increased the amount of non-rapid eye movement sleep (NREMS). The hypnotic effects of ?-oryzanol were comparable to those of the positive control doxepin, an H1R antagonist. In an in vivo mechanistic study, its hypnotic effects were completely blocked by the H1R agonist 2-pyridylethylamine. Additionally, neither ?-oryzanol nor doxepin increased NREMS or decreased sleep latency in H1R-KO mice. The results demonstrate that ?-oryzanol reduces sleep latency and promotes NREMS in mice via H1R antagonism.