Jin-Ho Jo

Hypnotic effects and binding studies for GABAA and 5-HT2C receptors of traditional medicinal plants used in Asia for insomnia

AIM OF THE STUDY Many medicinal plants have been used for treatment of insomnia in Asia. However, scientific evidence and precise mechanism for their sedative-hypnotic activity have not been fully investigated. Thus, we investigated the binding activity of the oriental plant extracts (mainly from Korea and Japan) to the well-known molecular targets for sleep regulation, GABA(A) and 5-HT(2C) receptors. Following the binding assay, sedative-hypnotic effects of the extracts with high affinity were examined in an animal model of sleep. MATERIALS AND METHODS Aqueous and ethanol extracts of 15 medicinal plants were tested for binding at the benzodiazepine site of GABA(A) receptor and 5-HT site of 5-HT(2C) receptor. The sedative-hypnotic effects of selected extracts were evaluated by measuring the sleep latency and sleep duration during pentobarbital-induced sleep in mice after oral administration of extracts. RESULTS In the GABA(A) assay, the ethanol extracts of licorice and danshen displayed concentration-dependent, high affinity binding, whereas in the 5-HT(2C) assay, the ethanol extracts of ginseng and silk tree showed high affinity. Among these extracts we tested previously uncharacterized licorice and silk tree for hypnotic effects. We found the ethanol extracts of licorice and silk tree significantly decreased sleep latency and increased sleep duration in pentobarbital-induced sleep. CONCLUSIONS We demonstrate for the first time that licorice and silk tree have the sedative-hypnotic activity possibly by modulating GABA(A) and 5-HT(2C) receptors. We propose that licorice and silk tree might be effective candidates for treatment of insomnia.

Isoliquiritigenin, a chalcone compound, is a positive allosteric modulator of GABAA receptors and shows hypnotic effects.

Isoliquiritigenin (ILTG) is a chalcone compound and has valuable pharmacological properties such as antioxidant, anti-inflammatory, anticancer, and antiallergic activities. Recently, the anxiolytic effect of ILTG has been reported; however, its action mechanism and hypnotic activity have not yet been demonstrated. Therefore, we investigated the hypnotic effect and action mechanism of ILTG. ILTG significantly potentiated the pentobarbital-induced sleep in mice at doses of 25 and 50mg/kg. The hypnotic activity of ILTG was fully inhibited by flumazenil (FLU), a specific gamma-aminobutyric acid type A (GABA(A))-benzodiazepine (BZD) receptor antagonist. The binding affinity of ILTG was 0.453 μM and was found to be higher than that of the reference compound, diazepam (DZP, 0.012 μM). ILTG (10(-5)M) potentiated GABA-evoked currents to 151% of the control level on isolated dorsal raphe neurons. ILTG has 65 times higher affinity for GABA(A)-BZD receptors than DZP, and the dissociation constant for ILTG was 4.0 × 10(-10)M. The effect of ILTG on GABA currents was blocked by 10(-7)M FLU and ZK-93426. These results suggest that ILTG produces hypnotic effects by positive allosteric modulation of GABA(A)-BZD receptors.

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%.

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.