• Korean Journal of Oriental Medicine
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• v.4 no.1 s.4
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• pp.99-114
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• 1998

The effect of herbal medicine on glutamate mediated neurotoxicity was studied in mouse neurons in primary culture. Immature cerebral cortex neurons (ED14) were maintained for up to 2 weeks in vitro, and we investigated the expression pattern of neuron differentiation and cytotoxicity of cell death, including LDH activity. Neuronal maturation initiated on day 7 and the susceptibility to glutamate-induced cell death was highly sensitive on Day 11 (Fig. 1). Thus, the exposure of the neurons to glutamate caused a dose$(0.1mM{\sim}1mM)$ and time$(4h{\sim}24h)$-dependent neurotoxicity(Fig. 4). Glutamate-induced neurodegeneration was prevented by Shipchondaebotang(SD), Yollyounggobondan(YG), Yugmijihwangwon(YJ) and the death of neurons exposed to glutamate was blocked by the NMDA receptor antagonist MK-801 (Fig. 5).

• Proceedings of the Zoological Society Korea Conference
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• 1998.10b
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• pp.250.1-250
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• 1998

No Abstract, See Full Text

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.303.2-304
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• 2002

Wogonin. a flavonoid originated from the root of Scutellaria baicalensis Georgi. is known to exhibit potent anti-inflammatory effects and variable degrees of antioxidant and free radical scavenging effects depending on the experimental systems. In addition. wogonin has been reported to protect neurons from excitotoxic and oxidative injuries in primary cultured rat cortical cells. (omitted)

• Proceedings of the Korean Society of Crop Science Conference
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• 2006.04a
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• pp.556-557
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• 2006

• Molecules and Cells
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• v.38 no.4
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• pp.312-317
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• 2015

Depletion of intracellular zinc by N,N,N,N-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) induces p53-mediated protein synthesis-dependent apoptosis of mouse cortical neurons. Here, we examined the requirement for poly(ADP-ribose) polymerase (PARP)-1 as an upstream regulator of p53 in zinc depletion-induced neuronal apoptosis. First, we found that chemical inhibition or genetic deletion of PARP-1 markedly attenuated TPEN-induced apoptosis of cultured mouse cortical neurons. Poly(ADP-ribosyl)ation of p53 occurred starting 1 h after TPEN treatment. Suggesting the critical role of PARP-1, the TPEN-induced increase of stability and activity of p53 as well as poly(ADP-ribosyl)ation of p53 was almost completely blocked by PARP inhibition. Consistent with this, the induction of downstream pro-apoptotic proteins PUMA and NOXA was noticeably reduced by chemical inhibitors or genetic deletion of PARP-1. TPEN-induced cytochrome C release into the cytosol and caspase-3 activation were also blocked by inhibition of PARP-1. Taken together, these findings indicate that PARP-1 is essential for TPEN-induced neuronal apoptosis.

• The Journal of Internal Korean Medicine
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• v.29 no.4
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• pp.835-845
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• 2008

Objectives : The purpose of this study was to investigate the effect of FS for the modulation of ROS and MMP in a hypoxic model of cultured rat cortical cells. Methods : For the effect of FS on the viability, FS was added to culture media (neurobasal supplemented with B27) and cell viability was measured by LDH assay. To investigate the effects of FS on ROS generation and MMP preservation, cells grown in FS-containing media were given a hypoxic shock(2% $O_2/5%$ $CO_2$, $37^{\circ}C$, 3 hrs) on DIV 10, stained with $H_2DCF-DA$(10 nM) and JC-1, respectively, and observed by fluorescent microscope. Results : 1. FS has a protective effect of cortical cells in both normoxia and hypoxia. 2. FS reduced the generation of ROS and this reduction was especially significant at 3 days after hypoxia. 3. FS was effective for the maintenance of MMP in hypoxia, and this efficacy was especially significant at 3 days after hypoxia. Conclusions : Taken together, these results indicate that FS attenuates ROS generation and MMP dissipation, which eventually protects from neuronal cell death in hypoxia.

• Journal of Life Science
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• v.14 no.2
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• pp.291-295
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• 2004

Rooibos (Aspalathus linearis) (RB) is a leguminous shrub native to the mountainous areas of the northwestern Cape Province in South Africa. RB tea infusions are the fermentation products of its leaves and fine sterns, and known to have a high antioxidative activity due to the presence of flavonoids and phenolic acids. We investigated the effects of RB tea on the alleviation of oxidative stress on cultured rat cortical neurons in a hypoxic model. Measurement of lactate dehydrogenase (LDH) released into culture media revealed that RB increased cell viabilities in both normoxia (6-18%) and hypoxia (2-24%) dose-dependently (10-100 $\mu\textrm{g}$/ml) on 16 days in vitro (3 days after treatment). Visualization of cell morphology by expression of GFP-Hsc70 fusion protein showed that RB (50 $\mu\textrm{g}$/ml) reduced the average vacuolated soma from 55.4$\pm$4.59% (no RB addition) to 40.9$\pm$6.3% (RB addition) on 5 days after hypoxia. Our results proves efficacy of RB in the neuroprotection of hypoxic neurons and extend application for RB into the prevention and/or treatment of neuronal damages.

• Proceedings of the Ginseng society Conference
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• 1998.06a
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• pp.47-56
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• 1998

In the present study, we assayed a number of compounds isolated from Panax ginseng C. A. Meyer (Araliaceae) for an ability to protect rat cortical cell cultures from the deleterious effects of the neurotoxicant, glutamate. We found that ginsenosides Rbl and Rg3 significantly attenuated glutamate-induced neurotoxicity. Brief exposure of cultures to excess glutamate caused extensive neuronal death. Glutamate-induced neuronal cell damage was significantly reduced by pretreatment with Rbl and Rgl. Ginsenosides Rbl and Rg3 inhibited the overproduction of nitric oxide which routinely follows glutamate neurotoxicity and preserved the level of superoxide dismutase in glutamate-treated cells. Furthermore, in cultures treated with glutamate, these ginsenosides inhibited the formation of malondialdehyde, a compound produced during lipid peroxidation, and diminished the influx of calcium. These results show that ginsenosides Rbl and Rg1 exerted significant neuroprotective effects on cultured cortical cells. As such, these compounds may be efficacious in protecting neurons from oxidative damage produced by exposure to excess glutamate.

• Journal of Life Science
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• v.19 no.5
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• pp.598-606
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• 2009

Oxidative stress by free radicals is a major cause of neuronal cell death. Excitotoxicity in hypoxia/ischemia causes an increase in reactive oxygen species (ROS) and a loss of mitochondrial membrane potential (MMP), resulting in dysfunction of the mitochondria and cell death. Pinelliae Rhizoma (PR) is a traditional medicine for incipient stroke. We investigated the effects of PR Water-Extract on the modulation of ROS and MMP in a hypoxic model using cultured rat cortical cells. PR Water-Extract was added to the culture medium at various concentrations (0.25${\sim}$5, 5.0 ${\mu}g/ml$) on day in vitro 12(DIV12), given a hypoxic shock (2% $O_2$/5% $CO_2$, $37^{\circ}C$, 3 hr), and cell viability was assessed on DIV15 by Lactate Dehydrogenase Assay (LDH assays). PR Water-Extract showed a statistically significant effect on neuroprotection (10${\sim}$15% increase in viability; p<0.01) at 1.0 and 2.5 ${\mu}g/ml$ in normoxia and hypoxia. Measurement of ROS production by $H_2DCF-DA$ stainings showed that PR Water-Extract efficiently reduced the number and intensity of ROS-producing neurons, especially at 1 hr post shock and DIV15. When MMP was measured by JC-1 stainings, PR Water-Extract efficiently maintained high-energy charged mitochondria. These results indicate that PR Water-Extract protects neurons in hypoxia by preventing ROS production and preserving the cellular energy level.

• Journal of Oriental Neuropsychiatry
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• v.21 no.1
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• pp.109-124
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• 2010

Objectives: This experiment was designed to investigate the effect of the InSamYangYoung-tang(Renshenyangrongtang) extract on $A{\beta}$-induced AD model. Methods: The effects of the InSamYangYoung-tang(Renshenyangrongtang) extract on neural damages of cultured PC12 cells induced by $A{\beta}$ were investigated. The effects of the InSamYangYoung-tang(Renshenyangrongtang) extract on neural damages of hippocampal and cortical neurons in the mouse induced by $\beta$-amyloid were investigated. Results: 1. $A{\beta}$ treatment into neuronal cells activated cell death pathway when analyzed by MTT assay and by histological analysis. Then InSamYangYoung-tang(Renshenyangrongtang) treatment improved cell survival to a similar level as in normal group. 2. $A{\beta}$ treatment increased caspase 3 protein levels but decreased phospho-Erk1/2 in neuronal cells. InSamYangYoung-tang(Renshenyangrongtang) treatment reversed the production levels of two proteins close to those in normal group. 3. $A{\beta}$ treatment induced the atrophy of neuronal cells in terms of neuronal processes and cell body shrinkage, but InSamYangYoung-tang(Renshenyangrongtang) greatly improved their morphology. 4. Neuroprotective activity, as observed in InSamYangYoung-tang(Renshenyangrongtang)-treated groups, was similarly observed in cells treated with galantamine which was used as a positive control. Moreover, overall recovery pattern by InSamYangYoung-tang(Renshenyangrongtang) was similar between cultured PC12 cells and in vivo hippocampal and cerebral cortical neurons in the mouse brain. Conclusions: This experiment shows that the InSamYangYoung-tang(Renshenyangrongtang) may play a protective role in neural tissues damaged by cytotoxic substances. Since neuronal damage seen in degenerative brains such as AD are largely unknown, the current data may provide possible insight into therapeutic strategies for AD treatments. InSamYangYoung-tang(Renshenyangrongtang) might be effective for the treatment of AD. Investigation into the clinical use of the InSamYangYoung-tang(Renshenyangrongtang) for AD is suggested for future research.