Min Young Um1,†, Sojin Kim2,†, Young-Ho Jin2, Minseok Yoon1, Hyejin Yang1, Jaekwang Lee1, Jonghoon Jung1, Yoshihiro Urade3, Zhi-Li Huang4, Sangoh Kwon5 and Suengmok Cho1,*
1 Division of Functional Food Research, Korea Food Research Institute, Seongnam, Republic of Korea
2 Department of Physiology, School of Medicine, Kyung Hee University, Seoul, Republic of Korea
3 International Institute for Integrative Sleep Medicine, University of Tsukuba, Japan
4 State Key Laboratory of Medical Neurobiology, Institute of Brain Sciences, Department of Pharmacology, Shanghai Medical College, Fudan University, Shanghai, China
5 S&D Research and Development Institute, Osong, Republic of Korea
† These authors contributed equally to the present work.
*Correspondence : Suengmok Cho
Scope : Although rice bran has been shown to be associated with a wide spectrum of health benefits, to date, there are no reports on its effects on sleep. We investigated the effect of rice bran on sleep and the mechanism underlying this effect.
Methods and results : Electroencephalography was used to evaluate the effects of standardized rice bran supplement (RBS) and doxepin hydrochloride (DH), a histamine H1 receptor (H1R) antagonist used as a positive control, on sleep in mice. The mechanism of RBS action was investigated using knockout (KO) mice and ex vivo electrophysiological recordings. Oral administration of RBS and DH significantly decreased sleep latency and increased the amount of non-rapid eye movement sleep (NREMS) in mice. Similar to DH, RBS fully inhibited H1R agonist-induced increase in action potential frequency in tuberomammillary nucleus neurons. In H1R KO mice, neither RBS nor DH administration led to the increase in NREMS and decrease in sleep latency observed in WT mice. These results indicate that the sleep-promoting effect of RBS is completely dependent on H1R antagonism.
Conclusions : RBS decreases sleep latency and promotes NREMS through the inhibition of H1R, suggesting that it could be a promising therapeutic agent for insomnia.
Keywords : Doxepin; Histamine H1 receptor; Hypnotic; Rice bran; Sleep