• Natural Product Sciences
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• v.18 no.3
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• pp.177-182
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• 2012

Oxidative stress potentially induces neurotoxicity which is believed to underlie several major age-related diseases of the central nervous system. This study sought to identify the cytoprotective effects of sixty-nine Cambodian plants against glutamate-induced cell death. Cultured HT22 cells were applied as an in vitro model, and neurotoxicity was induced in these neuronal cells by exposure to a determined concentration of glutamate. Sixty-nine plant sources, as Cambodia's indigenous species, were purchased from O'reusey Market, Phnom Penh, and extracted with ethanol. These extracts were screened for cytoprotective effects against glutamate-triggered neurotoxicity in HT22 cells at concentrations of 100 and 300 ${\mu}g/ml$. Of these, eight ethanol extracts, bark of Anacardium occidentale, bark and sapwood of Bauhinia pulla, flowers of Borassus flabellifer, stems and leaves of Coix lacryma-jobi, bark and sapwood of Diospyros nitida, sapwood of Dipterocarpus obtusifolius, stems of Oryza rufipogon, and fruits of Phyllanthus emblica, showed significant cytoprotective effects against glutamate-induced cell damage and degeneration in HT22 cells.

• YAKHAK HOEJI
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• v.40 no.6
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• pp.720-726
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• 1996

The neurotoxicity induced by L-glutamate in primary cultures of rat cortical cells could be attenuated by diterpene constituents of Ginkgo biloba leaves, ginkgolides A, B and C. At the concentration of 100 nM, ginkgolides up-regulated the activity of glutathione reductase in primary cultures of rat cortical cells exposed to 100 ${\mu}$M glutamate. Furthermore, ginkgolides increased the content of reduced glutathione in glutamate-treated cortical cells. However, ginkgolides showed little effect in reducing superoxide dismutase activity. Ginkgolides did, however, markedly block the production of malondialdehyde, a byproduct of lipid peroxidation in glutamate-treated rat cortical cells.

• YAKHAK HOEJI
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• v.41 no.1
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• pp.111-116
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• 1997

The neurotoxicity induced by L-glutamate in primary cultures of rat cortical cells could be attenuated by sesquiterpene constituent of Ginkgo biloba leaves, bilobalide. At the c oncentration of 100 nM, Bilobalide elevated the combined levels of reduced/oxidized glutathione in rat cortical cells exposed to 100 ${\mu}$M glutamate. Furthermore, bilobalide promoted a reduction in superoxide dismutase activity in glutamate-treated cells. Finally, bilobalide markedly inhibited the production of malondialdehyde. a measure of lipid peroxidation, in glutamate-treated rat cortical cells.

• Natural Product Sciences
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• v.14 no.3
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• pp.156-160
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• 2008

The methanolic extract of Rhus verniciflua Stokes (RVS-T) and its fractions (RVS-H, RVS-C, RVS-E and RVS-B) showed significant neuroprotective activity against glutamate-induced toxicity in primary cultures of rat cortical cells. RVS-B, which showed the most potent neuroprotective activity, was further fractionated to yield RVS-B5. Treatment of cortical cells with the RVS-T, RVS-B and RVS-B5 reduced the cellular ROS level and restored the reduced activities of glutathione reductase and SOD induced by glutamate. Although, the activity of glutathione peroxidase was not virtually changed by glutamate, RVS-B5 increased the glutathione peroxidase activity. In addition, these three tested fractions significantly restored the content of GSH which was decreased by glutamate insult in our cultures. Taken together, it could be postulated that RVS extract, in particular its fraction RVS-B5, protected neuronal cells against glutamate-induced neurotoxicity through acting on the antioxidative defense system.

• Korean Journal of Pharmacognosy
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• v.50 no.2
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• pp.118-123
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• 2019

Glutamate acts as an important neurotransmitter in brain. However, high concentration of glutamate showed an excitatory neurotoxicity and resulted to neuronal cell death. Neuronal cell death is known for one of the reason of Alzheimer's disease, a neurodegenerative disease. We tried to find neuroprotective medicinal plants by neuroprotection activity against glutamate injured HT22 cells as a model system. In the course of bioscreening of various medicinal plants, Taraxacum platycarpum extract showed significant neuroprotective activity. We tried to elucidate mechanisms of neuroprotective activity. T. platycarpum extract reduced ROS and intracellular $Ca^{2+}$ concentration increased by glutamate induced neurotoxicity. In addition, mitochondrial membrane potential was restored to the control level. Also, glutathione level, glutathione reductase and glutathione peroxidase activity were increased by T. platycarpum extract treatment. These data suggested that T. platycarpum showed neuroprotective activity via antioxidative activity.

• YAKHAK HOEJI
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• v.55 no.5
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• pp.385-390
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• 2011

Bee venom (BV), which is extracted from honeybees, has been used in traditional Korean medical therapy. Glutamate-mediated excitotoxicity contributes to neuronal death in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) or Alzheimer's disease (AD). This study is to investigate the effect of BV on glutamate-induced neurotoxicity on NSC-34 motor neuron cells. To determine the viability of motor neuronal cells, we performed with MTT assays in glutamate-treated NSC-34 cell with BV or without. For the measurement of oxidative stress, DCF assay was used in glutamate-treated NSC-34 motor neuronal cells with BV or without. To investigate the molecular mechanism of BV against glutamate-mediated neurotoxicity in NSC-34 cells, western blot analysis was used. Glutamate significantly decreased cell viability by glutamate dose- or treatment time-dependent manner in NSC-34 cells. However, BV pre-treatment dramatically inhibited glutamate-induced neuronal cell death. Furthermore, we found that BV increased the expression of Bcl-2 protein that is anti-apoptotic protein and reduced the generation of oxidative stress. BV has a neuroprotective role against glutamate neurotoxicity by an increase of anti-apoptotic protein. It suggests that BV may be useful for the reduction of neuronal cell death in neuronal disease models.

• Animal cells and systems
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• v.1 no.3
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• pp.467-473
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• 1997

Taurine (2-aminoethanesulfonic acid), one of bioactive amino acid in the mammalian brain, is known to exert inhibitory effects on neurons via GABA receptor. In the present study, we examined effects of taurine on glutamateinduced neurotoxicity on hippocampal neuron cell culture using cell counting method and lactate dehydrogenase (LDH) assay. After 10 d of culture, cells were stimulated with appropriate drugs. Only 43% of cultured neuronal cells survived at one day after stimulation with 500 uM L-glutamate for 10 min. Survival rate was enhanced by 82% in the presence of 10 mM taurine. LDH activity from the culture supernatant incubated with a combination of L-glutamate and taurine was less than half of that with L-glutamate alone. In the next series of experiments, interleukin-6 (IL-6) mRNA expression in cultured astrocytes was investigated using reverse tanscription-PCR (RT-PCR). IL-6 mRNA was detected in the astrocytes stimulated with L-glutamate in a dose-dependent manner, while not detected in the unstimulated control astrocytes. The expression of IL-6 mRNA caused by 10 mM glutamate was inhibited by taurine, but not by GABA. These findings demonstrated a neuroprotective action of taurine against glutamate-induced toxicity.

• YAKHAK HOEJI
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• v.56 no.5
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• pp.299-303
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• 2012

Homosyringaldehyde was isolated and identified from the 80% methanol extract of roots of Cynanchum paniculatum. C. paniculatum has been widely used for the treatment of various diseases such as neurasthenia, insomnia, dysmenorrheal and toothache. This compound exerted significant neuroprotective activities against glutamate-induced neurotoxicity in hippocampal HT22 cell line by 37.53% (at the concentration of $100{\mu}M$). We investigated mode of action of this compound. Homosyringaldehyde ($100{\mu}M$) significantly decreased the ROS level and $Ca^{2+}$ concentration in the oxidative stress induced HT22 cells by oxidative glutamate toxicity. Thus, our results suggest that homosyringaldehyde significantly protect HT22 cells against glutamate-induced oxidative stress, via antioxidative activities. As the results, we suggest that homosyringaldehyde may be useful in the treatment of neurogenerative disorders.

• Natural Product Sciences
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• v.14 no.3
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• pp.167-170
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• 2008

We previously reported that 90% MeOH fraction of Biota orientalis leaves (L.) ENDL. had significant neuroprotective activity against glutamate-induced neurotoxicity in primary cultures of rat cortical cells. In the present study, (-)-savinin (1), (-)-hinokinin (2), dehydroheliobuphthalmin (3) were isolated by bioactivity-guided fractionation from the 90% MeOH fraction. All three lignans had significant neuroprotective activities against glutamate-induced neurotoxicity at the concentrations ranging from 0.1 to 10.0 ${\mu}M$.

• Archives of Pharmacal Research
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• v.25 no.3
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• pp.349-356
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• 2002

The present study was performed to examine the effect of fangchinoline, a bis- benzylisoquinoline alkaloid, which exhibits the characteristics of a $Ca^{2+}$ channel blocker, on cyanide-induced neurotoxicity using cultured rat cerebellar granule neurons. NaCN produced a concentration-dependent reduction of cell viability, which was blocked by MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, verapamil, L-type$Ca^{2+}$channel blocker, and L-NAME, a nitric oxide synthase inhibitor. Pretreatment with fangchinoline over a concentration range of 0.1 to 10 $\mu$M significantly decreased the NaCN-induced neuronal cell death, glutamate release into medium, and elevation of $[Ca^{2+}]_i$ and oxidants generation. These results suggest that fangchinoline may mitigate the harmful effects of cyanide-induced neuronal cell death by interfering with $[Ca^{2+}]_i$influx, due to its function as a $Ca^{2+}$ channel blocker, and then by inhibiting glutamate release and oxidants generation.