Sleep-Promoting Effects and Possible Mechanisms of Action Associated with a Standardized Rice Bran Supplement

Abstract

Natural sleep aids are becoming more popular due to the widespread occurrence of sleep disorders. The objective of this study was to assess the sleep-promoting effects of rice bran-a product that is considered as a functional ingredient. To evaluate the sleep-promoting effects of a standardized rice bran supplement (RBS), we employed a pentobarbital-induced sleep test and conducted analyses of sleep architecture. In addition, the effect of RBS on a caffeine-induced sleep disturbance was investigated. Oral administration of RBS (500 and 1000 mg/kg) produced a significant decrease in sleep latency and increase in sleep duration in pentobarbital-induced sleep in mice. Moreover, both RBS (1000 mg/kg) and doxepin hydrochloride (histamine H₁ receptor antagonist, 30 mg/kg) counteracted a caffeine-induced sleep disturbance in mice. In terms of sleep phases, RBS (500 mg/kg) promoted non-rapid eye movement sleep for the first 3 h following its administration. Lastly, we unveiled a possible mechanism for RBS action as the hypnotic effect of RBS was blocked by a histamine H₁ receptor agonist. The present study revealed sleep-promoting effects of RBS using various animal assays. Such effects seem to be mediated through the histaminergic system. Our findings suggest that RBS may be a promising natural aid for relieving sleep problems.

Keywords: caffeine-induced arousal; histaminergic; hypnotic; rice bran; sleep-promoting.

Figure 1

Experimental procedures and timelines for the pentobarbital-induced sleep test (a) and polysomnographic recordings (b,c) showing typical EEG and EMG waveforms, and FFT spectra in mice. EEG, electroencephalogram; EMG, electromyogram; FFT, fast Fourier transform; REMS, rapid eye movement sleep; NREMS, non-REMS; Wake, wakefulness.

Figure 2

Effects of the administration of RBS or DOX on sleep latency (a) and sleep duration (b) in pentobarbital-treated (45 mg/kg, i.p.) ICR mice. Drugs were administered (p.o.) to mice 45 minutes before pentobarbital injection (i.p.). Each column represents mean ± SEM (n = 10). * p < 0.05, ** p < 0.01, significantly different when compared to the CON group (Dunnett’s test). CON, control; DOX, doxepin hydrochloride; RBS, rice bran supplement.

Figure 3

Effects of DOX (30 mg/kg) or RBS (1000 mg/kg) co-administration with caffeine (50 mg/kg) on sleep latency (a) and sleep duration (b) in pentobarbital-treated (45 mg/kg, i.p.) ICR mice. Drugs were administered (p.o.) to mice 45 min before pentobarbital injection (i.p.). Each column represents mean ± SEM (n = 10). ** p < 0.01, significantly different when compared to the CON group (Dunnett’s test). ## p < 0.01, significant difference between two groups. CON, control; DOX, doxepin hydrochloride; RBS, rice bran supplement.

Figure 4

Effect of RBS and DOX on sleep-wake profiles in C57BL/6N mice. (a) Representative EEG and EMG signals, and corresponding hypnograms in a mouse treated with RBS or DOX; (b) Effects of RBS and DOX on sleep latency; (c) Amounts of NREMS and REMS during the 3 h period after administration of RBS or DOX. Grey bars indicate the baseline day (vehicle). Each value represents the mean ± SEM of each group (n = 7–8). * p < 0.05, ** p < 0.01, significantly different from vehicle (unpaired Student’s t-test). RBS, rice bran supplement; DOX, doxepin hydrochloride; EEG, electroencephalogram; EMG, electromyogram; Wake, wakefulness; REMS, rapid eye movement sleep; NREMS, non-REMS; NS, no significance.

Figure 5

Effects of RBS (a) and DOX (b) on time-course changes in NREMS, REMS, and Wake during 24 h in C57BL/6N mice. Open and filled circles indicate the baseline day (vehicle) and experimental day (RBS or DOX), respectively. Each circle represents the hourly mean ± SEM (n = 7–8) of NREMS, REMS, and Wake. * p < 0.05, ** p < 0.01, significantly different from vehicle (unpaired Student’s t-test). The horizontal filled and open bars on the X-axis (clock time) indicate the 12-h dark and 12-h light periods, respectively. RBS, rice bran supplement; DOX, doxepin hydrochloride; Wake, wakefulness; REMS, rapid eye movement sleep; NREMS, non-REMS.

Figure 6

Characteristics of sleep-wake bouts in C57BL/6N mice during the 3 h period after administration of RBS and DOX. (a) Changes in the mean duration of Wake, NREMS, and REMS bouts; (b) Changes in the total number of Wake, NREMS, and REMS bouts. Grey bars indicate the baseline day (vehicle). Each value represents the mean ± SEM of each group (n = 7–8). * p < 0.05, ** p < 0.01, significantly different from vehicle (unpaired Student’s t-test). RBS, rice bran supplement; DOX, doxepin hydrochloride; Wake, wakefulness; REMS, rapid eye movement sleep; NREMS, non-REMS.

Figure 6

Characteristics of sleep-wake bouts in C57BL/6N mice during the 3 h period after administration of RBS and DOX. (a) Changes in the mean duration of Wake, NREMS, and REMS bouts; (b) Changes in the total number of Wake, NREMS, and REMS bouts. Grey bars indicate the baseline day (vehicle). Each value represents the mean ± SEM of each group (n = 7–8). * p < 0.05, ** p < 0.01, significantly different from vehicle (unpaired Student’s t-test). RBS, rice bran supplement; DOX, doxepin hydrochloride; Wake, wakefulness; REMS, rapid eye movement sleep; NREMS, non-REMS.

Figure 7

Effects of the GABA_A-BZD receptor antagonist, FLU, on changes in sleep latency (a) and sleep duration (b) in ICR mice treated with DZP (2 mg/kg) and RBS (1000 mg/kg). Drugs were administered (p.o.) to mice 45 min before the injection of pentobarbital (45 mg/kg, i.p.). FLU (8 mg/kg, i.p.) was injected 10 min before the administration of test samples. Each column represents mean ± SEM (n = 10). ** p < 0.01, significant difference when compared to the CON group (Dunnett’s test). ## p < 0.01, significant difference between treatment with FLU and treatment without FLU (unpaired Student’s t-test). CON, control; DZP, diazepam; FLU, flumazenil; NS, not significant; RBS, rice bran supplement.

Figure 8

Effects of the H₁R agonist, PEA, on changes in sleep latency (a) and sleep duration (b) in ICR mice treated with DOX (30 mg/kg) and RBS (1000 mg/kg). Drugs were administered (p.o.) to mice 45 min before the injection of pentobarbital (45 mg/kg, i.p.). PEA (150 mg/kg, i.p.) was injected 10 min before the administration of test samples. Each column represents mean ± SEM (n = 10). ** p < 0.01, significant difference when compared to the CON group (Dunnett’s test). ## p < 0.01, significant difference between treatment with PEA and treatment without PEA (unpaired Student’s t-test). CON, control; DOX, doxepin hydrochloride; NS, not significant; PEA, 2-pyridylethylamine dihydrochloride; RBS, rice bran supplement.