Minseok Yoon

Phlorotannins of the edible brown seaweed Ecklonia cava Kjellman induce sleep via positive allosteric modulation of gamma-aminobutyric acid type A-benzodiazepine receptor: A novel neurological activity of seaweed polyphenols

The primary objective was to investigate whether seaweeds have hypnotic activity. Methanol extracts of 30 seaweeds were screened for their binding activity at the GABA type A-benzodiazepine (GABAA-BZD) receptor, a well-characterised molecular target for sedative-hypnotics. The most active seaweed was Ecklonia cava Kjellman (ECK). An ethanol extract of ECK (ECK-E) significantly potentiated pentobarbital-induced sleep in mice. In four solvent fractions separated from ECK-E, hypnotic activity was proportional to contents of total phenols and total phlorotannins, known as seaweed polyphenols. Major phlorotannins of the ethyl acetate (EtOAc) fraction with the highest activity were eckol, eckstolonol, dieckol, and triphlorethol-A, and their Ki (binding affinity, μM) values for [3H]-flumazenil binding were 1.070, 1.491, 3.072, and 4.419, respectively. Hypnotic effects of ECK-E and the EtOAc fraction were fully inhibited by flumazenil, a specific GABAA-BZD receptor antagonist. These results imply that phlorotannins of ECK induce sleep by positive allosteric modulation of the GABAA-BZD receptor.

Enrichment and purification of marine polyphenol phlorotannins using macroporous adsorption resins

Phlorotannins are one of the most important bioactive polyphenols; however, their purification using chromatographic methods has not been explored. Here, we studied purification of phlorotannins from the crude phlorotannin extract (CPhE) of the brown seaweed Ecklonia cava using macroporous adsorption resins. For purification of phlorotannins, four resins (HP-20, SP-850, XAD-7HP, and XAD-2) were screened. Among them, HP-20 resin showed the highest adsorption and desorption capacities. In static adsorption tests, the adsorption capacity of HP-20 increased with increasing temperature (25-45°C). Optimal conditions for the dynamic experiments can be summarized as follows: total phlorotannin content (TPhC) in loading solution: 1.5mg PGE/mL, processing volume: 4 BV, flow rate: 1 mL/min, temperature: 45°C, desorption solvent: 40% ethanol solution. After purification, TPhC (452 mg PGE/g) and arsenic (180 μg/g) of CPhE increased and decreased to 905 mg PGE/g and 48 μg/g, respectively. Recovery rate of phlorotannins from CPhE was 92%.

Hypnotic effects and GABAergic mechanism of licorice (Glycyrrhiza glabra) ethanol extract and its major flavonoid constituent glabrol

Licorice (Glycyrrhiza glabra, GG) is one of the most frequently used herbal medicines worldwide, and its various biological activities have been widely studied. GG is reported to have neurological properties such as antidepressant, anxiolytic, and anticonvulsant effects. However, its hypnotic effects and the mechanism of GG and its active compounds have not yet been demonstrated. In this study, GG ethanol extract (GGE) dose-dependently potentiated pentobarbital-induced sleep and increased the amount of non-rapid eye movement sleep in mice without decreasing delta activity. The hypnotic effect of GGE was completely inhibited by flumazenil, which is a well-known γ-aminobutyric acid type A-benzodiazepine (GABA(A)-BZD) receptor antagonist, similar to other GABA(A)-BZD receptor agonists (e.g., diazepam and zolpidem). The major flavonoid glabrol was isolated from the flavonoid-rich fraction of GGE; it inhibited [(3)H] flumazenil binding to the GABA(A)-BZD receptors in rat cerebral cortex membrane with a binding affinity (K(i)) of 1.63 μM. The molecular structure and pharmacophore model of glabrol and liquiritigenin indicate that the isoprenyl groups of glabrol may play a key role in binding to GABA(A)-BZD receptors. Glabrol increased sleep duration and decreased sleep latency in a dose-dependent manner (5, 10, 25, and 50mg/kg); its hypnotic effect was also blocked by flumazenil. The results imply that GGE and its flavonoid glabrol induce sleep via a positive allosteric modulation of GABA(A)-BZD receptors.

Depressive effects on the central nervous system and underlying mechanism of the enzymatic extract and its phlorotannin-rich fraction from Ecklonia cava edible brown seaweed.

Marine plants have been reported to possess various pharmacological properties; however, there have been few reports on their neuropharmacological effects. Terrestrial plants have depressive effects on the central nervous system (CNS) because of their polyphenols which make them effective as anticonvulsants and sleep inducers. We investigated in this study the depressive effects of the polyphenol-rich brown seaweed, Ecklonia cava (EC), on CNS. An EC enzymatic extract (ECEE) showed significant anticonvulsive (>500 mg/kg) and sleep-inducing (>500 mg/kg) effects on the respective mice seizure induced by picrotoxin and on the mice sleep induced by pentobarbital. The phlorotannin-rich fraction (PTRF) from ECEE significantly potentiated the pentobarbital-induced sleep at >50 mg/kg. PTRF had binding activity to the gamma aminobutyric acid type A (GABAA)-benzodiazepine (BZD) receptors. The sleep-inducing effects of diazepam (DZP, a well-known GABAA-BZD agonist), ECEE, and PTRF were completely blocked by flumazenil, a well-known antagonist of GABAA-BZD receptors. These results imply that ECEE produced depressive effects on CNS by positive allosteric modulation of its phlorotannins on GABAA-BZD receptors like DZP. Our study proposes EC as a candidate for the effective treatment of neuropsychiatric disorders such as anxiety and insomnia.

Green and gold kiwifruit peel ethanol extracts potentiate pentobarbital-induced sleep in mice via a GABAergic mechanism.

Kiwifruit is one of the most popular fruits worldwide, and it has various biological properties, including antioxidant, anti-allergic, and cardiovascular protective effects. The peel of kiwifruit, which is a by-product of processing, is a good source of flavonoids; however, its bioactivity has not been widely investigated. In this study, we evaluated the hypnotic effects of green (GRPE, Actinidia deliciosa) and gold (GOPE, Actinidia chinensis) kiwifruit peel ethanol extracts and their solvent fractions, and the possible underlying mechanisms. Oral GRPE and GOPE administration (125-1000mg/kg) produced a dose-dependent decrease in sleep latency and an increase in sleep duration in pentobarbital-treated mice. Among three different solvent fractions of GRPE and GOPE, ethyl acetate (EA) fractions had the greatest effect on sleep duration at 250mg/kg. The total flavonoid contents of solvent fractions were proportional to sleep duration. Like diazepam (a GABA(A)-benzodiazepine (BZD) receptor agonist), the hypnotic effects of GRPE, GOPE, and their EA fractions were fully inhibited by flumazenil (a GABA(A)-BZD receptor antagonist). These results suggest that potentiation effects of GRPE and GOPE on pentobarbital-induced sleep in mice may be modulated by a GABAergic mechanism.

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.

Effects of Rice Flour Milling Types and Addition Methods on Rheological and Sensory Properties of Surimi Products

Surimi products are among the most prominent seafoods in Korea. Together with fish meat, wheat flour is a major ingredient in the preparation of surimi products. Rice flour, however, can be an effective ingredient in enhancing the rheological characteristics of surimi products. In this study, we evaluated the potential of rice flour as an agent to replace wheat flour in surimi products. The effects of rice flour milling types and addition methods on the rheological and sensory properties of surimi products were investigated. Among different addition methods, the surimi product containing non-treated rice flour showed better gel strength and sensory properties than products containing paste (1:1.3 rice flour/water, w/v) and steamed paste (steamed at for 30 min). According to the gel strength results for surimi products with added roll-mill (40 mesh) and jet-mill (180 mesh) rice flours, the roll-mill rice flour shows good potential as a replacement for wheat flour. When considering gel strength and sensory properties, an effective amount of rice flour to add was 10-15% (w/w). In conclusion, the rheological and sensory properties of surimi products containing rice flour were comparable with those of a premium commercial surimi product. Therefore, rice flour might be an effective alternative to wheat flour for premium surimi products.

Sleep-Promoting Effect of Ecklonia cava : Ethanol Extract Promotes Non-rapid Eye Movement Sleep in C57BL/6N Mice

Abstract We investigated the effects of Ecklonia cava ethanol extract (ECE) on sleep architecture and sleep profiles. ECE was orally admin-istered at a dose of 100, 250, or 500 mg/kg to C57BL/6N mice and its effects were measured by recording electroencephalogram (EEG) and electromyogram. Administration of ECE (250 and 500 mg/kg) significantly induced non-rapid eye movement sleep (NREMS) without affecting rapid eye movement sleep. The increase in NREMS by ECE (500 mg/kg) was significant ( P < 0.05) during the first 2 h after administration. In addition, ECE had no effect on EEG power density (an indicator of sleep quality) in NREMS. These results suggest that ECE induces NREMS in a manner similar to physiological sleep. Key words: Ecklonia cava , Electroencephalogram, Electromyogram, Non-rapid eye movement sleep, Delta power Introduction Ecklonia cava is a brown alga distributed in the coastal ar-eas of Jeju Island, Korea. It has been used as an ingredient in functional foods and traditional medicines (Cho et al., 2012b). Phlorotannins, fucoidans, fucoxanthins, and carotenoids have been identified as its major bioactive compounds (Heo et al., 2005; Kim and Bae, 2010). Extracts of this alga show various biological properties, including antioxidative (Li et al., 2009; Kim and Kim, 2010), immune-enhancing (Ahn et al., 2008, 2011), anti-allergic (Le et al., 2009; Shim et al., 2009), anti-cancer (Kong et al., 2009; Lee et al., 2011), and anti-inflam-matory (Kim and Bae, 2010) effects. Recently, the sedative-hypnotic effect of

Optimization of the Processing Conditions for the Preparation of Surimi Products Containing Rice Flour

Surimi (or fish paste) products are one of the most representative processed seafoods in Korea. In a previous study, we evaluated the potential use of rice flour as an agent to replace wheat flour in surimi products. In this study, we optimized the content of rice flour and water in surimi products using response surface methodology. Rice flour content ( X1, w/w) and water content (X2, v/w) were chosen as independent variables and gel strength (Y1) and overall acceptance (Y2) as dependent variables. Optimal conditions of X1 and X2 were 14% and 9.1%, respectively, and the predicted values of the multiple response optimal conditions were Y1 = 656.4 (g∙cm) and Y2 = 6.34. Under optimal conditions, the experimental values of Y1 and Y2 were 647.8 (g∙cm) and 6.21, respectively, which were similar to the predicted values. Surimi products that are prepared under optimum conditions were similar in gel strength to those of commercial products. However, its sensory evaluation score was higher than that of the commercial products. In conclusion, rice flour can not only be used as an alternative to wheat flour, but it also can be used to improve the quality of surimi products.

Effect of the licorice flavonoid isoliquiritigenin on the sleep architecture and profile in mice

The sleep-promoting effect of isoliquiritigenin (ILTG) was investigated by analyzing the sleep architecture in mice. A hypnotic diazepam (DZP, 2 mg/kg) significantly decreased sleep latency by 39.7% and increased the amount of non-rapid eye movement sleep (NREMS) by 103.8% for the first 3 h after administration. ILTG (50 mg/kg) also produced a significant decrease in sleep latency (30.7%) and an increase in the amount of NREMS (61.1%). DZP significantly decreased delta (0.5–4 Hz) activity as compared with the vehicle; however, ILTG did not alter the delta activity. These results mean that ILTG induces sleep similar to physiological sleep without a decline in sleep quality.