• The Journal of Korean Medicine
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• v.23 no.3
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• pp.211-222
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• 2002

Currently convulsion is considered to be a chronic central nerve disease characterized by involuntary and severe muscle contraction or spasm. In many recent studies, convulsion's mechanism is due to unbalance between stimulation and suppression of the central nerve system, such as GABA and glutamic acid. Objectives : This study was performed to examine the anticonvulsant effects of Podam-hwan on brain GABA levels and glutamate content in picrotoxin-induced convulsions and to determine the inhibitory activity on GABA transaminase. Methods : Brain GABA levels and glutamate content in the brains of picrotoxin-induced mice using reverse phase HPLC method, anticonvulsant effect in vivo, and the inhibitory effect on GABA transaminase activity in vivo have been investigated. Results : Podam-hwan significantly lengthened the onset time of picrotoxin-induced convulsion at a concentration of 15mg/kg, but did not show a dose-dependent pattern. Also, Podam-hwan shortened the duration of convulsion by 52.2% at a dose of 30mg/kg in comparison with the control group. Podam-hwan inhibited dose-dependently GABA transaminase activity by 35.5% at 30mg/kg, comparing with the control gmup. Podam-hwan also increased the brain GABA level by 38.7% and 68.8% at doses 15mg/kg and 30mg/kg, respectively. In addition, Podam-hwan decreased the brain glutamate level by 9.6% and 17.8% at doses 15mg/kg and 30mg/kg, respectively. Conclusions : Podam-hwan can be prescribed for the treatment of convulsion by enhancement of brain GABA level and inhibition of GABA transaminase activity.

• BMB Reports
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• v.31 no.3
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• pp.233-239
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• 1998

A GABA synthesizing enzyme, glutamate decarboxylase, has been purified from bovine brain by several chromatographic procedures. The preparation appeared homogeneous on SDS-PAGE. The enzyme is a homodimeric protein with a molecular mass of 120 kDa. The activation of glutamate decarboxylase by ginesenosides from Panax ginseng C.A. Meyer has been studied. Preincubation of the enzyme with total ginsenoside, $Rb_2$ and Rc ginsenosides, increased glutamate decarboxylase activities in a dose-dependent manner. There was a reproducible decrease in $K_m$, in addition to a increase in $V_{max}$, in response to increasing concentrations of the Rc ginsenoside fraction. Upon addition of the ginsenoside to the enzyme, a decrease in flurorescence intensity was discernible, together with an increase in emission anisotropy. Judging from the anisotropy values, the ginsenoside is rapidly trapped by the protein matrix. Total ginsenoside was administered to rats and the rat brains were removed for the measurement of the changes of GABA shunt regulating enzyme activities. Among the GABA shunt regulating enzymes, only the glutamate decarboxylase activities were increased after ginsenoside treatment. Therefore, it is suggested that the ginsenosides may elevate the GABA level in brain by activation of glutamate decarboxylase and the enzymatic activation might be due to the conformational change induced by binding of ginsenoside to the enzyme.

• Journal of Oriental Neuropsychiatry
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• v.18 no.3
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• pp.83-95
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• 2007

This study was performed to examine the anticonvulsant effects of the extracts of JeongGan-Tang and explanation of its action mechanism. Method: 1) The inhibitory effect on convulsions induced by pentylenetetrazole, picrotoxin and strychnine was investigated in vivo 2) The inhibitory effect on GABA transaminase activity was evaluated in vivo and in vitro. 3) The brain GABA level and glutamate level in pentylenetetrazole-induced convulsion model were analyzed by HPLC, Results: 1) JeongGan-Tang showed the significant effect on the pentylenetetrazole-induced convulsion, which may mean that its anticonvulsant effect would be resulted from the activation of GABA receptor and chloride channel rather than the presynaptic- or postsynaptic inhibition. 2) JeongGan-Tang exhibited proper inhibitory activity on GABA transaminase in vitro and in vivo. 3) JeongGan-Tang increased the brain GABA level but did not affect the brain glutamate content, which may suggest that this drug supresses the convulsion by increase of GABA, an inhibitory neurotransmitter. Conclusion : JeongGan-Tang can be used as an anticonvulsant prescription by the modulation of GABAergic neurotramission.

• Journal of Oriental Neuropsychiatry
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• v.19 no.1
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• pp.43-54
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• 2008

Objective: The aim of this study is to evaluate the anticonvulsive effects of Gamiheichumhwan extract and to explain its action in GABAergic neuromodulation of the rat brain. Method: The extracts of Gamiheichumhwan were investigated for their inhibitory effect on GABA transaminase activity, their influence on brain GABA and glutamate levels, their agonistic activity on GABA/benzodiazepine receptor and anticonvulsive action using in vitro and in vivo assays. Results: 1. The extract inhibited dose-dependently GABA transaminase (GABA-T) activity by 4.6% and 18.9%, respectively at dosages of 250 mg/kg and 500mg/kg mouse (p.o.). 2. Brian GABA level was increased to 72.0% and brain glutamate level was decreased to 9.6% at a dosage of 500 mg/kg mouse (p.o.). 3. The extract suppressed [3H]Ro15-1788 binding to rat cerebral cortical membrane by $81.4{\pm}0.8%$ at a dosage of 3.2 mg, suggesting its agonistic activity on GABA/benzodiazepin receptor. 4. The extract showed anticonvulsive effect by lengthening the onset time of convulsion, shortening the convulsion duration and diminishing the lethality. Conclusion : It is suggested that Gamiheichumhwan can be used to somnipathy and adapted to treatment and prevention of epilepsy or convulsion.

• The Journal of Korean Medicine
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• v.25 no.1
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• pp.188-197
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• 2004

Objective and Methods : This study was performed to evaluate the anticonvulsant, antioxidant effect of modified formulas Korean traditional medicine Cheongsinhwadam-Jeon(CSHDJ). The extract of CSHDJ was administered (p.o.) to mice for 14 days in anticonvulsant and antioxidant tests. Results : The pretreatment of CSHDJ extract prohibited pentylenetrazol (PTZ)-induced convulsion. In PTZ-induced convulsion, lowered level of brain ${\gamma}$-aminobutyric acid(GABA) was restored normal state by the pretreatment of CSHDJ. Increased level of brain glutamic acid was lowered to normal state by CSHDJ, and increased activity of brain ${\gamma}-aminobutyric$ acid transaminase(GABA-T) was reduced to normal state by CSHDJ. In PTZ-induced convulsion, increased level of brain lipid peroxide was lowered to normal state by the pretreatment of CSHDJ. Increased activity of brain xanthine oxidase(XOD) was lowered by CSHDJ, and increased activity of brain aldehyde oxidase lowered to normal state by CSHDJ. In PTZ-induced convulsion, increased activities of superoxide dismutase(SOD) and catalase in brain were lowered by the pretreatment of CSHDJ, whereas increased level of glutathione and increased activity of gluthathione peroxidase in brain were not changed significantly. Conclusions : Above results suggest that CSHDJ has anticonvulsant, antioxidant effect. That seems to be strongly related with the levels of GABA, glutamate, lipid peroxide and the activities of GABA-T, XOD, aldehyde oxidase, SOD, catalase in brain tissue. From these results, CSHDJ could be applied to various convulsive disorders.

• Archives of Pharmacal Research
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• v.26 no.6
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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.

• Journal of Pharmacopuncture
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• v.26 no.4
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• pp.327-337
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• 2023

Objectives: Epilepsy is a neurological condition characterized by repeated seizures attributable to synchronous neuronal activity in the brain. The study evaluated the effect of acetone extract of Adansonia digitata stem bark (ASBE) on seizure score, cognition, depression, and neurodegeneration as well as the level of Gamma-Aminobutyrate acid (GABA) and glutamate in Pentylenetetrazol-kindled rats. Methods: Thirty-five rats were assigned into five groups (n = 7). Groups 1-2 received normal saline and 35 mg/kg PTZ every other day. Groups 3-4 received 125 mg/kg and 250 mg/kg ASBE orally while group 5 received 5 mg/kg diazepam daily for twenty-six days. Group 3-5 received PTZ every other day, 30 mins after ASBE and diazepam. Results: The results showed that Pentylenetetrazol (PTZ) induces seizure, reduces mobility time in force swim test and decreases the normal cell number in the brain. It also significantly decreases (p < 0.05) catalase, superoxide dismutase and reduced glutathione activities compared to the ASBE pre-treated rats. Pre-treatment with ASBE reportedly decreases seizure activities significantly (p < 0.05) and increases mobility time in the force swim test. ASBE also significantly elevate (p < 0.05) the normal cell number in the hippocampus, temporal lobe, and dentate gyrus. Conclusion: ASBE reduced seizure activity and prevented depression in PTZ-treated rats. It also prevented neurodegeneration by regulating glutamate and GABA levels in the brain as well as preventing lipid peroxidation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.1
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• pp.206-213
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• 2004

This study was performed to evaluate the anticonvulsant, antioxidant effect of modified formulas Korean traditional medicine Gungchihwadam-Jeon(GCHDJ). The extract of GCHDJ was administered (p.o.) to mice for 14 days in anticonvulsant and antioxidant tests. The pretreatment of GCHDJ extract prohibited the pentylenetrazol(PTZ)-induced convulsion in PTZ-induced convulsion, lowered level of brain r-aminobutyric acid(GABA) was restored by the pretreatment of GCHDJ. Increased level of brain glutamic acid was lowered to normal state by GCHDJ, and increased activity of brain r-aminobutyric acid transaminase(GABA-T) was reduced by GCHDJ. In PTZ-induced convulsion, increased level of brain lipid peroxide was lowered to normal state by the pretreatment of GCHDJ. Increased activity of brain xanthine oxidase(XOD) was lowered to normal state by GCHDJ, and increased activity of brain aldehyde oxidase lowered to normal state by GCHDJ. In PTZ-induced convulsion, increased activities of superoxide dismutase(SOD) and catalase in brain were lowered by the pretreatment of GCHDJ, whereas increased level of glutathione and increased activity of gluthathione peroxidase in brain were not changed significantly. Above results suggest that GCHDJ have anticonvulsant. antioxidant effect. That seems to be strongly related with the levels of GABA, glutamate, lipid peroxide and the activities of GABA-T, XOD, aldehyde oxidase, SOD, catalase in brain tissue. From these results, GCHDJ could be applied to various convulsive disorders.

• Journal of Life Science
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• v.28 no.5
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• pp.597-604
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• 2018

Although the core mechanisms of Attention Deficit/Hyperactivity Disorder (ADHD) are unknown, several ADHD-associated proteins have been studied. G-protein - coupled receptor kinase interacting protein-1 (GIT1) is a multifunctional adapter protein that affects neuron growth and dendrite formation. GIT1-deficient mice have shown ADHD-like behavior and also recovered through amphetamine treatment. In this study, gliotransmitters were investigated in both intracellular and extracellular space from GIT1-deficient mice. To measure the amount of gliotransmitters, primary astrocyte cultures were taken from the cerebral and cerebellar cortices of wild (WT), hetero (HE), and knock-out (KO) mice. Major gliotransmitters were analyzed using high-performance liquid chromatography. It was observed that the amount of excitatory and inhibitory gliotransmitters were dependent on genotype and showed a change in excitation/inhibition ratios. Interestingly, the major excitatory gliotransmitter, glutamate, existed at the lowest level in WT mice, but the amount of inhibitory gliotransmitters, gamma-aminobutyric acid (GABA) and glycine, varied depending on brain region. Remarkably, an increased amount of GABA was measured at the intracellular cerebrum in WT mice compared with KO mice. It was presumed that KO mice would secrete more inhibitory gliotransmitters to compensate for GIT1 depletion or else acquire a defect to reuptake-secreted GABA. This may be a possible mechanism for ADHD pathology.

• Journal of Food Hygiene and Safety
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• v.37 no.1
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• pp.21-28
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• 2022

In this study, a new lactic acid bacterium (LAB) that could produce gamma-aminobutyric acid (GABA) was isolated from Oenanthe javanica (water celery) and identified as an Enteroccoccus casseliflavus strain. Until recently, there have been many studies on the gamma-aminobutyric acid producing lactic acid bacterium, as well as on some lactic acid bacterium in Enteroococcs genus, but none on the species E. casseliflavus. Therefore, in the purpose of finding the optimal conditions for GABA production of E. casseliflavus PL05, the effects of several conditions including the type of mediums, growth temperatures, initial pH, growth time, L-mono sodium glutamate (MSG) concentration, and carbon source were tested. The study revealed that the PL05 strain grew better in the Brain Heart Infusion (BHI) medium than in the Man, Rogosa, and Sharpe (MRS) or Tryptic Soy Broth (TSB) medium. Also, similar results were obtained with GABA production conditions. As a result of analysis on the GABA production yield by concentration of MSG, a GABA substrate, the highest production was found at 7% of MSG concentration. However, since similar level of production was found at 5%, it is considered to be more efficient to use 5% MSG concentration. The analysis on the growth and GABA production yield by carbon sources showed the highest results when maltose was used. From the final test under the optimal conditions found, 140.06±0.71 mM of GABA was produced over 24 hours with the conversion rate of 78.95%. Lastly, from the sensitivity analysis on the 10 different antibiotics, including vancomycin, it was found that there were not confirmed cases of resistance.