• The Korean Journal of Pain
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• 제28권1호
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• pp.4-10
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• 2015

Etifoxine (etafenoxine, $Stresam^{(R)}$) is a non-benzodiazepine anxiolytic with an anticonvulsant effect. It was developed in the 1960s for anxiety disorders and is currently being studied for its ability to promote peripheral nerve healing and to treat chemotherapy-induced pain. In addition to being mediated by $GABA_A{\alpha}2$ receptors like benzodiazepines, etifoxine appears to produce anxiolytic effects directly by binding to ${\beta}2$ or ${\beta}3$ subunits of the $GABA_A$ receptor complex. It also modulates $GABA_A$ receptors indirectly via stimulation of neurosteroid production after etifoxine binds to the 18 kDa translocator protein (TSPO) of the outer mitochondrial membrane in the central and peripheral nervous systems, previously known as the peripheral benzodiazepine receptor (PBR). Therefore, the effects of etifoxine are not completely reversed by the benzodiazepine antagonist flumazenil. Etifoxine is used for various emotional and bodily reactions followed by anxiety. It is contraindicated in situations such as shock, severely impaired liver or kidney function, and severe respiratory failure. The average dosage is 150 mg per day for no more than 12 weeks. The most common adverse effect is drowsiness at the initial stage. It does not usually cause any withdrawal syndromes. In conclusion, etifoxine shows less adverse effects of anterograde amnesia, sedation, impaired psychomotor performance, and withdrawal syndromes than those of benzodiazepines. It potentiates $GABA_A$ receptor-function by a direct allosteric effect and by an indirect mechanism involving the activation of TSPO. It seems promising that non-benzodiazepine anxiolytics including etifoxine will replenish shortcomings of benzodiazepines and selective serotonin reuptake inhibitors according to animated studies related to TSPO.

• Archives of Pharmacal Research
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• 제26권6호
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• pp.487-492
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• 2003

This study investigated the effects of extremely low frequency magnetic fields (ELF-MFs) on the sensitivity of seizure response to bicuculline, picrotoxin and NMDA in mice. The mice were exposed to either a sham or 20 G ELF-MFs for 24 hours. Convulsants were then administered i.p. at various doses. The seizure induction time and duration were measured and lethal dose ($LD_{50$}) and convulsant dose ($CD_{50}$) of the clonic and tonic convulsion were calculated. The analysis of glutamate, glycine, taurine and GABA of mouse brain was accomplished by HPLC. The mice exposed to ELF-MFs showed moderately higher $CD_{50}.{\;}LD_{50}$ and onset time on the bicuculline-induced seizure. However, the ELF-MFs did not influence them in the NMDA and picrotoxin-induced seizures. After the exposure to MFs exposure, the glutamate level was increased and GABA was decreased significantly in NMDA and picrotoxin-induced seizure. The level of glutamate and GABA were not changed by MFs in bicuculline-induced seizure. These results suggest that ELF-MFs may alter the convulsion susceptibility through GABAergic mechanism with the involvement of the level of glutamate and GABA.

• The Korean Journal of Physiology and Pharmacology
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• 제24권5호
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• pp.433-440
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• 2020

The substantia gelatinosa (SG) of the trigeminal subnucleus caudalis (Vc) is the first relay site for the orofacial nociceptive inputs via the thin myelinated Aδ and unmyelinated C primary afferent fibers. Borneol, one of the valuable time-honored herbal ingredients in traditional Chinese medicine, is a popular treatment for anxiety, anesthesia, and antinociception. However, to date, little is known as to how borneol acts on the SG neurons of the Vc. To close this gap, the whole-cell patch-clamp technique was applied to elucidate the antinociceptive mechanism responding for the actions of borneol on the SG neurons of the Vc in mice. In the voltage-clamp mode, holding at -60 mV, the borneol-induced non-desensitizing inward currents were not affected by tetrodotoxin, a voltage-gated Na⁺ channel blocker, 6-cyano-7-nitro-quinoxaline-2,3-dione, a non-N-methyl-ᴅ-aspartate (NMDA) glutamate receptor antagonist and DL-2-amino-5-phosphonopentanoic acid, an NMDA receptor antagonist. However, borneol-induced inward currents were partially decreased in the presence of picrotoxin, a γ-aminobutyric acid (GABA)_A receptor antagonist, or strychnine, a glycine receptor antagonist, and was almost suppressed in the presence of picrotoxin and strychnine. Though borneol did not show any effect on the glycine-induced inward currents, borneol enhanced GABA-mediated responses. Beside, borneol enhanced the GABA-induced hyperpolarization under the current-clamp mode. Altogether, we suggest that borneol contributes in part toward mediating the inhibitory GABA and glycine transmission on the SG neurons of the Vc and may serve as an herbal therapeutic for orofacial pain ailments.

• 한국미생물·생명공학회지
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• 제50권3호
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• pp.319-327
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• 2022

γ-Aminobutyric acid (GABA) is a multi-functional compound with broad applications for food industry. GABA producing bacteria were isolated from cabbage kimchi. Among them, B737 was the best GABA producer when culture supernatants were analyzed by TLC. B737 was identified as Levilactobacillus brevis by 16S rRNA gene sequencing. Its glutamate decarboxylase (GAD) gene was cloned by PCR and the nucleotide sequence determined. B737 GAD consisting of 485 amino acids is the largest in size among GADs reported from LAB so far. gadB from L. brevis B737 was overexpressed in Escherichia. coli BL21(DE3) using pET26b(+).pET26b(+). The recombinant GAD was purified and its size was 55 kDa by SDS-PAGE. Maximum GAD activity was observed at pH 5 and 40℃ and the activity was dependent on pyridoxal 5'-phosphate. K_m and V_max of recombinant GAD were 6.2 ± 0.06 mM and 0.34 ± 0.002 mM/min, respectively. L. brevis B737 can be used as a starter for fermented foods with high GABA contents.

• 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)].

• Food Science and Biotechnology
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• 제18권6호
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• pp.1398-1403
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• 2009

Present study deals with variations of physicochemicals including $\gamma$-aminobutyric acid (GABA), $\gamma$-oryzanol, free sugar, lipoxygenase activity, fat acidity, and germination rate from Korean brown rice cultivars. With increase of storage time and temperature, GABA, $\gamma$-oryzanol, lipoxygenase activity, and fat acidity increased, whereas free sugar and germination rate was reduced. Among cultivars, 'Gopumbyeo' exhibited the highest contents in GABA and $\gamma$-oryzanol during 12 weeks storage at $25^{\circ}C$ (GABA: $28.6{\pm}5.6{\rightarrow}170.4{\pm}4.6\;mg/100\;g$, $\gamma$-oryzanol: $6.1{\pm}0.7{\rightarrow}6.7{\pm}0.4\;mg/g$) and 'Ilpumbyeo' significantly decreased in free sugar during 12 weeks storage at $10^{\circ}C$ ($1,423.7{\rightarrow}1,058.4\;mg/100\;g$). Moreover, 'Taebongbyeo' exhibited the highest quality owing to low lipoxygenase activity, low fat acidity, and high germination rate. In free sugar compositions, sucrose exhibited the highest content (>70%), followed by fructose (>7%), raffinose (>5%), glucose (>3%), and maltose (>2%) during storage. Based on our results, changes of physicochemicals in stored brown rice may be important information in processing food and functional properties.

• Preventive Nutrition and Food Science
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• 제13권3호
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• pp.219-224
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• 2008

In this study, we investigated changes in some physico-chemical and biochemical properties of Kimchi during fermentation and storage. After fermenting Kimchi at $15^{\circ}C$ for 23, 36, 40, 44, and 60 hrs during the first week, we stored it at $-1^{\circ}C$ in a Kimchi refrigerator until the end of 8th week. The pH of samples fermented for 36 hr, 40 hr, 44 hr and 60 hr sharply decreased during the first seven days and then slowly decreased. Acidities of samples fermented for 36 hr, 40 hr and 44 hr sharply increased for the first seven days. According to measured changes of lactic acid bacteria number, samples fermented for 60 hr revealed the largest augmentation in the number of lactobacilli for the first seven days. The $\gamma$-aminobutyric acid (GABA) content of the sample fermented for 40 hr was the most superior, with an early increase and maintenance of GABA content, which maintained a maximum 20 mg per 100 g of Kimchi sample on the seventh, fourteenth, and twenty eighth days. These results suggest that relatively enhanced levels of GABA in Kimchi samples can be produced and maintained by controlling the fermentation and storage processes, as with the 40 hr fermented sample conditions.

• 한국환경농학회지
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• 제30권4호
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• pp.402-408
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• 2011

BACKGROUND: Effect of various light wavelength and plant defense molecules were evaluated on the hardness and the contents of free amino acid including ${\gamma}$-aminobutyric acid (GABA) in soybean sprouts. METHODS AND RESULTS: Germinating soybean seeds were treated with various single wavelength of light (380, 440, 470, and 660 nm) or without light at $25^{\circ}C$ for six days. Soybean seeds were also treated with stress-signaling molecule ethephon or $H_2O_2$ at the same time. Soybean sprouts treated with 470 nm substantially raised the hardness almost two times than the control. The free amino acid contents were higher in 470 nm and $H_2O_2$ treated soybean seeds than the control. Nutritionally beneficial GABA contents were increased by the treatments of 470 nm, 440 nm, ethephon, and $H_2O_2$. CONCLUSION: These results suggest that the hardness and the contents of amino acids can be regulated by stimuli, which stimuli could be composed of various wavelength and plant defense molecules. Especially, single wavelength 470 nm illumination has the effect of increasing GABA contents with increased hardness.

• The Korean Journal of Physiology and Pharmacology
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• 제15권5호
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• pp.285-289
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• 2011

Shilajit, a medicine herb commonly used in Ayurveda, has been reported to contain at least 85 minerals in ionic form that act on a variety of chemical, biological, and physical stressors. The substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) are involved in orofacial nociceptive processing. Shilajit has been reported to be an injury and muscular pain reliever but there have been few functional studies of the effect of Shilajit on the SG neurons of the Vc. Therefore, whole cell and gramicidin-perfotrated patch clamp studies were performed to examine the action mechanism of Shilajit on the SG neurons of Vc from mouse brainstem slices. In the whole cell patch clamp mode, Shilajit induced short-lived and repeatable inward currents under the condition of a high chloride pipette solution on all the SG neurons tested. The Shilajit-induced inward currents were concentration dependent and maintained in the presence of tetrodotoxin (TTX), a voltage gated $Na^+$ channel blocker, CNQX, a non-NMDA glutamate receptor antagonist, and AP5, an NMDA receptor antagonist. The Shilajit-induced responses were partially suppressed by picrotoxin, a $GABA_A$ receptor antagonist, and totally blocked in the presence of strychnine, a glycine receptor antagonist, however not affected by mecamylamine hydrochloride (MCH), a nicotinic acetylcholine receptor antagonist. Under the potassium gluconate pipette solution at holding potential 0 mV, Shilajit induced repeatable outward current. These results show that Shilajit has inhibitory effects on the SG neurons of Vc through chloride ion channels by activation of the glycine receptor and $GABA_A$ receptor, indicating that Shilajit contains sedating ingredients for the central nervous system. These results also suggest that Shilajit may be a potential target for modulating orofacial pain processing.

• Bulletin of the Korean Chemical Society
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• 제19권8호
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• pp.883-884
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• 1998