• The Korean Journal of Food And Nutrition
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• v.30 no.6
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• pp.1364-1369
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• 2017

There is a growing demand for natural sleep aids due to various side effects of long-term administration of pharmacological treatments for insomnia. Honey has been reported to exhibit numerous potential health benefits, and it is hypothesized that honey may favorably affect insomnia treatment. Therefore, this study was performed to investigate the possible hypnotic effect of clover honey (CH) and to determine its in vivo mechanism. The total flavonoid content (TFC) of CH and fractions extracted with ethylacetate (EtOAc) and $H_2O$ was measured. The pentobarbital-induced sleep test using $GABA_A$-benzodiazepine (BZD) agonists and antagonists was conducted to evaluate the potential mechanism of action behind the sedative-hypnotic activity of CH in mice. The results showed that administration of 500 and 1,000 mg/kg of CH significantly (p<0.01) reduced the sleep latency to a level similar to that of diazepam (DZP, 2 mg/kg), and 1,000 mg/kg of CH significantly (p<0.01) prolonged the sleep duration, which was comparable to that of DZP (2 mg/kg). Administration of the EtOAc fraction with a higher TFC significantly reduced the sleep latency at 50 to 200 mg/kg and prolonged the sleep duration at 100 to 200 mg/kg, which were comparable to those after administration of DZP (2 mg/kg). However, co-administration of CH and EtOAc with flumazenil, a specific $GABA_A-BZD$ receptor antagonist, blocked the hypnotic effect. Our findings suggest that the hypnotic activity of CH may be attributed to allosteric modulation of $GABA_A-BZD$ receptors. The TFC of CH is expected to be a key factor that contributes to its hypnotic effect.

• Journal of Yeungnam Medical Science
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• v.16 no.1
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• pp.25-33
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• 1999

Benzodiazepines(BZDs) are among the most widely prescribed drugs in the world. They are potent anxiolytic, antiepileptic, hypnotic, and muscle relaxing agents. There is an emerging model of the role of several neural systems in anxiety and their relation to the mechanism of action of BZDs. It has been postulated that BZD drugs exert their anxiolytic action by regulating GABAergic transmission in limbic areas such as the amygdala, in the posterior hypothalamus, and in the raphe nuclei. The involvement of the amygdala in the behaviors triggered by fear and stress has been suggested by many previous studies. In this review, reports about regulatory effects of endogenous BZD receptor ligands on the perception of anxiety and memory consolidation were summerized. These findings further support the contention that BZD receptor ligands modulate memory consolidation of averse learning tasks by influencing the level of stress and/or anxiety that accompanies a learning experience. The findings suggest that the decrease in the limbic levels of BZD-like molecules seen after the various behavioral procedures represent a general response to stress and/or anxiety, since it occurs in proportion to the level of stress and/or anxiety that accompany these tasks. In addition, these findings further support the hypothesis that the $GABA_A$/BZD receptor complex in limbic structures plays a pivotal role in the stress and anxiety.