• 한국축산식품학회지
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• 제37권5호
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• pp.646-653
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• 2017

Alcalase hydrolysis of liquid egg white was used to produce 5-hydroxytryptophan (HTP) under various conditions and investigate the sleep-potentiating activity of liquid egg white hydrolysate (LEH) on pentobarbital-induced sleep. Alcalase hydrolysis yielded the highest content of 5-HTP ($13.50{\mu}g/mL$), while neutrase hydrolysis showed the lowest 5-HTP content ($5.23{\mu}g/mL$). The liquid egg white to water ratio (1:1) was optimal for the production of 5-HTP with high amino-nitrogen (A-N) content and degree of hydrolysis. The 5-HTP, amino-nitrogen, and degree of hydrolysis increased until 24 h of hydrolysis and slightly increased thereafter during hydrolysis with 2% and 5% enzyme addition. 5-HTP administration at doses of 6 and 9 mg/kg significantly increased sleep duration and decreased sleep latency time compared to that in the control (p<0.05). LEH (150 mg/mouse), which was equivalent to 5-HTP at 6 mg/kg, significantly decreased sleep latency time and increased sleep duration time compared to that in the control (p<0.05). Oral administration of LEH showed sleep-potentiating effects because of 5-HTP. The sleep-potentiating activity of LEH may have occurred through 5-HTP in our pentobarbital-induced sleep model. LEH may be a valuable alternative to sleep enhancement and may be used as a sleep-potentiating agent.

• Natural Product Sciences
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• 제18권2호
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• pp.67-75
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• 2012

Zizyphi Spinosi Semen (ZSS) have been widely used for the treatment of insomnia in Asia. This experiment was performed to investigate whether methanol extract of ZSS (MEZSS) has hypnotic effects through the ${\gamma}$-amino butyric acid (GABA)ergic systems. MEZSS inhibited the locomotor activity. MEZSS enhanced pentobarbital-induced sleep behaviors. However, MEZSS itself did not induce sleep at higher dose, similar to muscimol. On the other hand, both pentobarbital and MEZSS increased the non rapid eye move (NREM) sleep, especially reducing the -wave electroencephalogram (EEG) activity in REM sleep. MEZSS showed similar effects with muscimol on potentiating chloride influx induced by pentobarbital. MEZSS significantly increased GABAA receptors ${\gamma}$-subunit expression and slightly decreased ${\beta}$-subunit expression in hypothalamus and thalamus, showing that subunit-expression was similar to diazepam. In addition, MEZSS enhanced the expression of glutamic acid decarboxylase (GAD). In conclusion, it is suggested that MEZSS might augment pentobarbital-induced sleep behaviors through the modification of GABAergic systems.

• Archives of Pharmacal Research
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• 제15권2호
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• pp.184-186
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• 1992

Malonic acid amides were synthesized using different amino acids and their esters. THe synthesized compounds were evaluated for their sedative activity on rats. Potentiating effect of all the compounds on pentobarbitone induced sleep on rats was observed. Plasma protein binding studies were also carried out and it was observed that the synthesized compounds have low plasma protein binding as compared to barbiturates.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2008년도 Proceedings of the Convention
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• pp.119-142
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• 2008

Zizyphi Spinosi Semen (ZSS) has been widely used for the treatment of anxiety and insomnia in Korea and China. This experiment was performed to know whether sanjoinine A, one of major alkaloid compounds of ZSS has anxiolytic and hypnotic effects through the GABAergic systems. Our results showed that administration of sanjoinine A increased open arm entries and spent time in open arm in the elevated plus-maze and increased head dips in hole board test. Different from traditional anxiolytic, diazepam, sanjoinine A itself did not decrease locomotor activity and strength level in mice. Furthermore, Sanjoinine A (0.5-2.0 mg/kg) prolonged sleeping time and reduced sleeping latency induced by pentobarbital in a dose-dependent manner similar to muscimol, a $GABA_A$ receptor agonist. Sanjoinine A (0.25-1.0 mg/kg) also increased sleeping rate and sleeping time in the combined administration at the sub-hypnotic dose of pentobarbital and showed synergic effects with muscimol in potentiating sleeping onset and enhancing sleeping time induced by pentobarbital. However, sanjoinine A itself did not induce sleeping at the higher dose. In addition, both of sanjoinine A and pentobarbital increased chloride influx in primary cultured cerebellar granule cells. Sanjoinine A decreased the $GABA_A$ receptor ${\alpha}$-subunit expression and increased ${\gamma}$-subunit expression, and had no effects on abundance of ${\beta}$-subunit in primary cultured cerebellar granule cells, showing different expression of subunits from pentobarbital. In conclusion, sanjoinine A shows anxiolytic-like effects and augments pentabarbital-induced sleeping behaviors through the modification of GABAergic systems. [This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (The Regional Research Universities Program/Center for Healthcare Technology Development)].