• Natural Product Sciences
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• v.21 no.3
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• pp.219-225
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• 2015

In the previous experiments, we reported that ethanol extract of Gastrodiae Rhizoma, the dried tuber of Gastrodia ElataBlume (Orchidaceae) increased pentobarbital-induced sleeping behaviors. These experiments were undertaken to know whether 4-hydroxybenzaldehyde (4-HBD), is one of the major compounds of Gastrodiae Rhizoma increases pentobarbital-induced sleeping behaviors and changes sleep architectures via activating GABA_A-ergic systems in rodents. 4-HBD decreased locomotor activity in mice. 4-HBD increased total sleep time, and decreased of sleep onset by pentobarbital (28 mg/kg and 40 mg/kg). 4-HBD showed synergistic effects with muscimol (a GABA_A receptor agonist), shortening sleep onset and enhancing sleep time on pentobarbital-induced sleeping behaviors. On the other hand, 4-HBD (200 mg/kg, p.o.) itself significantly inhibited the counts of sleepwake cycles, and prolonged total sleep time and non-rapid eye movement (NREM) in rats. Moreover, 4-HBD increased intracellular Cl⁻ levels in the primary cultured cerebellar cells. The protein levels of glutamic acid decarboxylase (GAD) and GABA_A receptors subunits were over-expressed by 4-HBD. Consequently, these results demonstrate that 4-HBD increased NREM sleep as well as sleeping behaviors via the activation of GABA_A-ergic systems in rodents.

• Natural Product Sciences
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• v.23 no.1
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• pp.53-60
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• 2017

Perillae Herba has been traditionally used for the sedation in the oriental countries. Therefore, this study was conducted to determine whether Perillae Herba ethanol extract (PHEE) enhances pentobarbital-induced sleeping behaviors in animals. In addition, the possible mechanisms are demonstrated. PHEE (12.5, 25 and 50 mg/kg. p.o.) reduced the locomotor activity in mice. PHEE reduced sleep latency and augmented the total sleep time in pentobarbital (42 mg/kg, i.p.)-induced sleep in mice. Furthermore, the number of sleeping mice treated with sub-hypnotic pentobarbital (28 mg/kg, i.p.) increased. PHEE (50 mg/kg. p.o.) decreased the sleep/wake cycles and wakefulness, and increased total sleeping time and NREM sleep in electroencephalogram (EEG) of rats. In addition, PHEE (0.1, 1.0 and $10{\mu}g/ml$) increased the intracellular $Cl^-$ level through the GABA receptors in the hypothalamus of rats. Moreover, the protein of glutamate decarboxylase (GAD) was overexpressed by PFEE. It was found that PHEE enhanced pentobarbital-induced sleeping behaviors through $GABA_A-ergic$ transmissions.

• Journal of Dairy Science and Biotechnology
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• v.27 no.1
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• pp.45-51
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• 2009

$\gamma$-aminobutyric acid (GABA) is a ubiquitous nonprotein amino acid that is produced primarily by $\alpha$-decarboxylation of L-glutamic acid (Glu) catalyzed by the enzyme glutamate decarboxylase (GAD). It is well known as a neurotransmitter that regulates inhibitory neurotransmission in the mammalian central nervous system. In addition, GABA has been proved to be effective for lowering blood pressure in mammals. This paper is intended to provide basic information about GABA, including the functional and biological activity of GABA, GABA production by lactic acid bacteria, and the utilization of GABA in the production of dairy products.

• Journal of Mushroom
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• v.13 no.4
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• pp.334-337
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• 2015

${\gamma}$-Aminobutyric acid (GABA) is basically neurotrasmitter produced by the decarboxylation of L-glutamic acid catalyzed by glutamic acid decarboxylase (GAD), which was known to convert monosodium glutamate (MSG) to GABA. To investigate enhancement of reversion rate of GABA, the yogurt fermentation with addition of nanoparticle winter mushroom and hydroponic ginseng was used. The conversion rate was revealed to nanoparticle winter mushroom and hydroponic ginseng fermenter (88%) > winter mushroom fermenter (52%) > nanoparticle winter mushroom fermenter (44%). The results showed that nanoparticle winter mushroom and hydroponic ginseng supplemented substrates for enhancement of GABA may be used more effectively as one of potential sources of functional foods.

• Biomolecules & Therapeutics
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• v.25 no.2
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• pp.105-111
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• 2017

It has been known that RA, one of major constituents of Perilla frutescens which has been used as a traditional folk remedy for sedation in oriental countries, shows the anxiolytic-like and sedative effects. This study was performed to know whether RA may enhance pentobarbital-induced sleep through ${\gamma}-aminobutyric$ acid $(GABA)_A-ergic$ systems in rodents. RA (0.5, 1.0 and 2.0 mg/kg, p.o.) reduced the locomotor activity in mice. RA decreased sleep latency and increased the total sleep time in pentobarbital (42 mg/kg, i.p.)-induced sleeping mice. RA also increased sleeping time and number of falling sleep mice after treatment with sub-hypnotic pentobarbital (28 mg/kg, i.p.). In electroencephalogram (EEG) recording, RA (2.0 mg/kg) not only decreased the counts of sleep/wake cycles and REM sleep, but also increased the total and NREM sleep in rats. The power density of NREM sleep showed the increase in ${\delta}-waves$ and the decrease in ${\alpha}-waves$. On the other hand, RA (0.1, 1.0 and $10{\mu}g/ml$) increased intracellular $Cl^-$ influx in the primary cultured hypothalamic cells of rats. RA (p.o.) increased the protein expression of glutamic acid decarboxylase ($GAD_{65/67}$) and $GABA_A$ receptors subunits except ${\beta}1$ subunit. In conclusion, RA augmented pentobarbital-induced sleeping behaviors through $GABA_A-ergic$ transmission. Thus, it is suggested that RA may be useful for the treatment of insomnia.

• Natural Product Sciences
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• v.18 no.2
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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.

• Biomolecules & Therapeutics
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• v.22 no.4
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• pp.314-320
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• 2014

This study was investigated to know whether pachymic acid (PA), one of the predominant triterpenoids in Poria cocos (Hoelen) has the sedative-hypnotic effects, and underlying mechanisms are mediated via ${\gamma}$-aminobutyric acid (GABA)-ergic systems. Oral administration of PA markedly suppressed locomotion activity in mice. This compound also prolonged sleeping time, and reduced sleep latency showing synergic effects with muscimol (0.2 mg/kg) in shortening sleep onset and enhancing sleep time induced by pentobarbital, both at the hypnotic (40 mg/kg) and sub-hypnotic (28 mg/kg) doses. Additionally, PA elevated intracellular chloride levels in hypothalamic primary cultured neuronal cells of rats. Moreover, Western blotting quantitative results showed that PA increased the amount of protein level expression of $GAD_{65/67}$ over a broader range of doses. PA increased ${\alpha}$- and ${\beta}$-subunits protein levels, but decreased ${\gamma}$-subunit protein levels in $GABA_A$ receptors. The present experiment provides evidence for the hypnotic effects as PA enhanced pentobarbital-induced sleeping behaviors via $GABA_A$-ergic mechanisms in rodents. Taken together, it is proposed that PA may be useful for the treatment of sleep disturbed subjects with insomnia.

• Journal of Microbiology and Biotechnology
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• v.16 no.4
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• pp.562-568
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• 2006

GABA $(\gamma-aminobutyric\;acid)$ is the principal inhibitory neurotransmitter in the brain. For the efficient production of GAB A, a semi continuous cell entrapment system using Lactobacillus brevis GABA 057 was optimized, including the substrate concentration, bead-stabilizing additives, and reaction conditions. The converted monosodium glutamate (MSG), which was added as a substrate for glutamic acid decarboxylase (GAD), increased from 2% (w/v) to 12% (w/v). The addition of isomaltooligosaccharide to the alginate beads also increased the stability of the entrapped L. brevis and GABA productivity. Consequently, when optimal conditions were applied, up to 223 mM GABA could be produced from 534 mM MSG after 48 h of reaction by using alginate-beadencapsulated L. brevis GABA 057.

• Journal of Life Science
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• v.27 no.5
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• pp.567-574
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• 2017

This study is to isolate and identify ${\gamma}$-amino butyric acid (GABA) producing lactic acid bacteria (LAB) from Makgeolii, traditional Korean rice wine and then establish the optimal culture conditions for GABA production. Sixty four LAB from Makgeolli were isolated according to the characteristics of the shape and color of the colony grown on MRS agar plate. The GABA production of the isolated strain cultured in MRS broth contained 1% MSG (mono-sodium glutamate) were determined and evaluated by TLC and HPLC analysis. Strain B-134 was selected for highest GABA production. From the analysis of 16S rRNA and glutamate decarboxylase B (gadB) gene sequences, strain B-134 was tentatively identified as a Lactobacillus plantarum subsp. plantarum B-134. Effects of culture parameters, including glutamic acid level, culture temperature, NaCl level, and pH on GABA production were investigated for culture optimization. The optimum culture condition for GABA production by B-134 were culture temperature of $37^{\circ}C$, pH of 5.7, NaCl content of 0% (w/v) and MSG content of 3% (w/v), which produced 25 mM of GABA during cultivation time of 48 hr. From these results, strain B-134 is expected to be utilized as useful microorganisms for GABA-enriched health beneficial food.

• Natural Product Sciences
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• v.22 no.4
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• pp.263-269
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• 2016

Rhynchophylline (RP) is a major tetracyclic oxindole alkaloid of Uncariae Ramulus et Uncus which has been used to treat hypertension, seizures, pain and anxiety in the oriental countries. A recent report revealed that RP attenuated ischemia-induced neuronal damage and kainite-induced convulsions in animals. This study was performed to investigate whether RP enhances pentobarbital-induced sleep behaviors and modulates sleep architecture in mice. Locomotor activity was significantly inhibited by RP at 0.25 and 0.5 mg/kg, similar to 2 mg/kg diazepam (a benzodiazepine agonist) in mice. RP shortened sleep latency and increased total sleep time in a dose-dependent manner when administrated with pentobarbital (42 mg/kg, i.p.). RP also increased the number of sleeping mice and total sleep time by concomitant administration with the sub-hypnotic dosage of pentobarbital (28 mg/kg, i.p.). On the other hand, RP (0.25 mg/kg, p.o.) itself significantly inhibited sleep-wake cycles, prolonged total sleep time, and rapid eye movement in rats. In addition, RP also increased chloride influx in the primary cultured hypothalamic neuronal cells. In addition, we found that glutamic acid decarboxylase ($GAD_{65/67}$) was activated by RP. In conclusion, RP augments pentobarbital-induced sleeping behaviors, and can be a candidate for treating insomnia.