Min Young Um

α-pinene, a major constituent of pine tree oils, enhances non-rapid eye movement sleep in mice through GABAA-benzodiazepine receptors

α-Pinene is a major monoterpene of the pine tree essential oils. It has been reported that α-pinene shows anxiolytic and hypnotic effects upon inhaled administration. However, hypnotic effect by oral supplementation and the molecular mechanism of α-pinene have not been determined yet. By combining in vivo sleep behavior, ex vivo electrophysiological recording from brain slices, and in silico molecular modeling, we demonstrate that (−)-α-pinene shows sleep enhancing property through a direct binding to GABAA-benzodiazepine (BZD) receptors by acting as a partial modulator at the BZD binding site. The effect of (−)-α-pinene on sleep-wake profiles was evaluated by recording electroencephalogram and electromyogram. The molecular mechanism of (−)-α-pinene was investigated by electrophysiology and molecular docking study. (−)-α-pinene significantly increased the duration of non-rapid eye movement sleep (NREMS) and reduced the sleep latency by oral administration without affecting duration of rapid eye movement sleep and delta activity. (−)-α-pinene potentiated the GABAA receptor-mediated synaptic response by increasing the decay time constant of sIPSCs in hippocampal CA1 pyramidal neurons. These effects of (−)-α-pinene on sleep and inhibitory synaptic response were mimicked by zolpidem, acting as a modulator for GABAA-BZD receptors, and fully antagonized by flumazenil, an antagonist for GABAA-BZD receptor. (−)-α-pinene was found to bind to aromatic residues of α1- and -γ2 subunits of GABAA-BZD receptors in the molecular model. We conclude that (−)-α-pinene enhances the quantity of NREMS without affecting the intensity of NREMS by prolonging GABAergic synaptic transmission, acting as a partial modulator of GABAA-BZD receptors and directly binding to the BZD binding site of GABAA receptor.

Enhanced Cognitive Effects of Demethoxycurcumin, a Natural Derivative of Curcumin on Scopolamine-Induced Memory Impairment in Mice.

In the present study, we examined the ameliorating effects of demethoxycurcumin (DMC) on memory impairment induced by scopolamine using passive avoidance and Morris water maze tests in mice. Moreover, to determine the neurobiological effects underlying the ameliorating effects of the DMC, choline acetyltransferase (ChAT) immunoreactivity was evaluated in mice exposed to scopolamine. Our results demonstrated that chronic oral administration (28 days) of DMC (10 mg/kg) improved scopolamine-induced learning impairment in the passive avoidance task and memory impairment in the Morris water maze. Moreover, Choline acetyltransferase (ChAT) activity in the DMC-treated group was significantly increased to 33.03% compared with the control group. Our present finding suggests that DMC ameliorates memory impairments induced by scopolamine treatment through reversing the reduction of hippocampal ChAT expression in mice.

Rice bran supplement prevents UVB-induced skin photoaging in vivo

Abstract Although rice bran consumption is reportedly has numerous beneficial effects on human health, the relationship between rice bran and the prevention of photoaging has not been investigated in detail. We sought to investigate whether consumption of rice bran supplement (RBS) can elicit preventive effects against UVB-induced photoaging in vivo. Dorsal skin sections of hairless mice were exposed to UVB over 16 weeks. RBS consumption suppressed UVB-induced wrinkle formation and inhibited the loss of water content and epidermal thickening in the mouse skin. Western blot and immunohistochemical analyses revealed that repeated exposure to UVB upregulated matrix metalloproteinase-13 (MMP-13) and cyclooxygenase-2 (COX-2) expression, while consumption of RBS suppressed MMP-13 and COX-2 expression, as well as mitogen-activated protein kinase (MAPK) signaling pathways. These findings suggest that RBS could be a potential bioactive ingredient in nutricosmetics to inhibit wrinkle formation and water content loss via the suppression of COX-2 and MMP-13 expression. Effect of RBS on UVB-irradiated COX-2 and MMP-13 expression in SKH-1 hairless mouse skin.

Monitoring and Optimization of the Effects of the Blending Ratio of Corn, Sesame, and Perilla Oils on the Oxidation and Sensory Quality of Seasoned Laver Pyropia spp.

Seasoned laver Pyropia spp. is one of the most well-known Korean traditional seafoods, and is becoming more popular worldwide. Various mixed oils are used in the preparation of seasoned laver; however, there is no information available regarding the effects of the blending ratio of oils on the quality of seasoned laver. In this study, the effects of the blending ratio of corn, sesame, and perilla oils on the oxidation and sensory quality of seasoned laver were monitored and optimized using a response surface methodology. An increase in the proportion of corn and sesame oils resulted in an excellent oxidation induction time, whereas a high ratio of perilla oil reduced the thermal oxidative stability of the mixed oil. In the sensory test, the seasoned laver with the highest propor- tion of sesame oil was preferred. The optimal blending ratio (v/v) of corn, sesame, and perilla oils for both oxidation induction time (Y1) and sensory score (Y2) was 92.3, 6.0, and 1.7%. Under optimal conditions, the experimental values of Y1 and Y2 were 4.41 ± 0.3 h and 5.58 ± 0.8 points, and were similar to the predicted values (4.34 h and 5.13 points). Our results for the monitoring and optimization of the blending ratio provide useful information for seasoned laver processing companies.

Phlorotannin supplement decreases wake after sleep onset in adults with self‐reported sleep disturbance: A randomized, controlled, double‐blind clinical and polysomnographic study

Our previous study demonstrated that phlorotannin supplement had a sleep‐promoting effect in rodents. In the present study, we investigated whether the phlorotannin supplement could improve sleep in subjects with self‐reported sleep disturbances. In a randomized, double‐blind, placebo‐controlled trial, 24 subjects consumed either a placebo or phlorotannin supplement (500 mg/day) for 1 week, 30–60 min prior to bedtime. Sleep parameters were assessed at baseline and at 1 week with sleep questionnaires and polysomnography. At the end of the treatment period, the complete sets of sleep parameters from 20 subjects. Phlorotannin resulted in a significant increase in “Sleep duration” scores compared to the placebo (p = .044), although there were no significant differences on the total PSQI scores. Polysomnography revealed that wakefulness after sleep onset was significantly lower in the phlorotannin group compared to the placebo group (phlorotannin vs. placebo, −25.5 ± 30.5 vs. −1.7 ± 14.9; p = .045) as well as total wake time (phlorotannin vs. placebo, −0.9 ± 3.0 vs. −6.1 ± 6.8; p = .048). Additionally, the respiratory disturbance index during supine rapid eye movement sleep was significantly lower in the phlorotannin group (p = .035). There were no serious adverse effects in either group. Our data suggest that the phlorotannin supplement improved sleep maintenance (WHO ICTRP: KCT0001892).

Chlorogenic Acid from Hawthorn Berry (Crataegus pinnatifida Fruit) Prevents Stress Hormone‐Induced Depressive Behavior, through Monoamine Oxidase B‐Reactive Oxygen Species Signaling in Hippocampal Astrocytes of Mice

SCOPE Oxidative stress has been implicated in mental disorders, including depression. Chlorogenic acid (CGA), one of the abundant phenolic compounds in herbs and fruits, has the properties of a natural antioxidant and free-radical scavenger. Therfore, we investigated the antidepressant-like effects and active mechanisms of CGA from the extract of Crataegus pinnatifida (CP) fruit. METHODS AND RESULTS Depression-like phenotypes were induced in mice by daily injection of stress hormone for 1-2 weeks. The brains of these animals exhibited reduced brain-derived neurotrophic factor expression and increased astrocytic hypertrophy, which are typical markers of depression in animal models. Stress hormone injection 1) upregulated monoamine oxidase B (MAOB) expression and 2) reduced spine numbers along neuronal dendrites, which indicates synaptic depression. The oral administration of CGA (30 mg kg-1 ) or CP (300 mg kg-1 ) prevented MAOB activation following reactive oxygen species (ROS) production and had an ameliorative effect on depressive behavioral tests (e.g., tail suspension and forced swim tests). In vitro assays performed on cultured C8-D1A cells revealed that CGA and CP inhibited MAOB activity and ROS production. CONCLUSION Our study indicates that CGA and CP extracts prevented depressive behavior and thereby have potential as natural antidepressants.

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

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.

A novel neurological function of rice bran: a standardized rice bran supplement promotes non-rapid eye movement sleep in mice through histamine H1 receptors

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 (H1 R) 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 H1 R agonist-induced increase in action potential frequency in tuberomammillary nucleus neurons. In H1 R 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 H1 R antagonism. CONCLUSIONS RBS decreases sleep latency and promotes NREMS through the inhibition of H1 R, suggesting that it could be a promising therapeutic agent for insomnia.

Extraction Optimization for Phlorotannin Recovery from the Edible Brown Seaweed Ecklonia Cava

ABSTRACT Phlorotannins, marine polyphenols from the brown seaweeds, are a promising biologically active substance. This study aimed to optimize the extraction conditions for phlorotannin recovery from the brown seaweed Ecklonia cava using response surface methodology. Ethanol concentration (X1, %), extraction temperature (X2, °C), and extraction time (X3, h) were chosen as independent variables. The dependent variables were total phlorotannin content (TPhC; Y1) and yield of phlorotannins (Y2). Estimated optimal conditions were as follows: TPhC (Y1): X1 = 95%, X2 = 80°C, X3 = 22.8 h, and yield of phlorotannins (Y2): X1 = 88.3%, X2 = 80°C, X3 = 24 h. Predicted values of dependent variables under each optimal condition were TPhC (Y1) = 570.2 mg phloroglucinol equivalents/g (mg PGE/g, dry basis) and yield of phlorotannins (Y2) = 7.8% and were similar to the experimental values. In addition, content of dieckol, which is known as an indicator of phlorotannin products, was measured. Dieckol contents of the phlorotannin extracts with the highest (565.7 mg PGE/g) and lowest (315.4 mg PGE/g) TPhC were 49.1 and 34.4 mg/g (dry basis), respectively.