• Journal of Ginseng Research
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• v.37 no.3
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• pp.315-323
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• 2013

Ginseng is known to have antistress effects. Previously, red ginseng (RG) was shown to repress stress-induced peptidyl arginine deiminase type IV (PADI4) via estrogen receptor ${\beta}$ ($ER{\beta}$) in the brain, thus inhibiting brain cell apoptosis. Moreover, tumor necrosis factor (TNF)-${\alpha}$ plays a critical role in immobilization (IMO) stress. However, the signaling pathway of RG-mediated repressesion of inflammation is not completely understood. In this study, we determined how RG modulated gene expression in stressed brain cells. Since secretion of TNF-${\alpha}$ is modulated via TNF-${\alpha}$ converting enzyme (TACE) and nuclear factor (NF)-${\kappa}B$, we examined the inflammatory pathway in stressed brain cells. Immunohistochemistry revealed that TACE was induced by IMO stress, but RG repressed TACE induction. Moreover, PADI4 siRNA repressed TACE expression compared to the mock transfected control suggesting that PADI4 was required for TACE expression. A reporter assay also revealed that $H_2O_2$ oxidative stress induced NF-${\kappa}B$ in neuroblastoma SK-N-SH cells, however, RG pretreatment repressed NF-${\kappa}B$ induction. These findings were supported by significant induction of nitric oxide and reactive oxygen species (ROS) by oxidative stress, which could be repressed by RG administration. Taken together, RG appeared to repress stress-induced PADI4 via TACE and NF-${\kappa}B$ in brain cells thus preventing production of ROS and subsequently protecting brain cells from apoptosis.

• Biomolecules & Therapeutics
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• v.12 no.3
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• pp.189-193
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• 2004

Over the past several years, research efforts have been directed both at economically producing valuable substances from the wood biomass and at producing lignolytic enzymes at a lower cost. In the present study, we found that Phellinus igniarius, the basidiomycetes, secreted lignin peroxidase as a main lignolytic enzyme, which was detected maximum activity at 16th day of culture and showed 37 kDa of molecular mass in identification by activity assay and purification by anion-exchange chromatography. The Phellinus igniarius-derived lignin peroxidase hydrolyzed steam-exploded wood (Quercus mongolica) powder into small molecules showing cytotoxicity against cancer cel1s (HepG2 hepatoma, SK-N-SH neuroblastoma, B16 melanoma, MBT-2 bladder cancer). In addition, the enzyme hydrlysates of lignins (ELg) that were extracted from the steam-exploded oak showed more potent cytotoxic effects on the cancer cells than the enzyme hydrolysates of wood biomass (EWp), indicating that the cytotoxic effect of EWp may be due to the enzyme-degraded products of lignin among the lignocellulosics. Furthermore, the cytotoxic effect of ELg on Chang, normal liver cells, was much less potent than that of ELg on HepG2 and B16 cancer cells, indicating that the cytotoxic effect of ELg may be specific for cancer cells. The present results suggest that Phellinus igniarius may be a useful resource for the large-scale production of lignin peroxidase and that the lignin peroxidase may be applied for the generation of valuable biodegradation products from wood lignocellulosics for medical use.

• Journal of Life Science
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• v.22 no.8
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• pp.1099-1106
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• 2012

The cytotoxicity of the colorant in conjugated linoleic acid (CLA) was investigated in human cancer cell lines and a normal human cell line. Commercially-available CLA with a brown color (designate crude CLA; c-CLA) was distilled in a vacuum (10 mmHg-$220^{\circ}C$, 10 mmHg-$235^{\circ}C$, 10 mmHg-$240^{\circ}C$, and 20 mmHg-$260^{\circ}C$) for 30 min to obtain pure CLA (distilled CLA; d-CLA) and dark brown-colored CLA (residual CLA; r-CLA) samples. No color intensity was shown in the d-CLA sample obtained under 10 mmHg-$220^{\circ}C$ conditions of distillation when the L (brightness), a (red/blue), and b (yellow/green) parameters were analyzed, whereas the r-CLA sample showed a dark brown color. The composition of CLA isomers in both the d- and r-CLA samples, as compared to that of the c-CLA sample, was not significantly different when analyzed by gas chromatography. When the cytotoxicity of the r-CLA and d-CLA samples obtained under 10 mmHg-$220^{\circ}C$ conditions were compared against human breast cancer cells (MCF-7), human lung cancer cells (A-549), human colon cancer cells (HT-29), human prostate cancer cells (PC-3), and human neuroblastoma cells (SK-N-SH), no significant cytotoxicity was seen in the cell lines. These results suggest that the color or colorant in the CLA samples did not have any effects on the proliferation of human cancer and normal cells and imply that the colorant in commercially available CLA samples is safe for human consumption.

• Archives of Pharmacal Research
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• v.27 no.10
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• pp.1073-1079
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• 2004

Interactions of the cell adhesion molecules are known to play important roles in mediating inflammation. The proinflammatory cytokine, tumor necrosis factor-${\alpha}$(TNF-${\alpha}$), activates the NF-kB signaling pathway, which induces the expression of various genes, such as intercellular adhesion molecule-1 (ICAM-1). In this study, the effect of vitamin C on the ICAM-1 expression induced by TNF-${\alpha}$ in a human neuroblastoma cell line, SK-N-SH was investigated. Treatment with vitamin C resulted in the downregulation of the TNF-${\alpha}$-induced surface expression and ICAM-1 mRNA levels in a concentration-dependent manner. Moreover, a gel shift analysis indicated that vitamin C dose-dependently inhibited the NF-kB activation and IkB${\alpha}$ degradation induced by TNF-${\alpha}$. Taken together, these results suggest that vitamin C downregulates TNF-${\alpha}$- induced ICAM-1 expression via the inhibition of NF-kB activation.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.3
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• pp.149-156
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• 2011

Golgi SNAP receptor complex 1 (GS28) has been implicated in vesicular transport between intra-Golgi networks and between endoplasmic reticulum (ER) and Golgi. Additional role(s) of GS28 within cells have not been well characterized. We observed decreased expression of GS28 in rat ischemic hippocampus. In this study, we examined the role of GS28 and its molecular mechanisms in neuronal (SK-N-SH) cell death induced by hydrogen peroxide ($H_2O_2$). GS28 siRNA-transfected cells treated with $H_2O_2$ showed a significant increase in cytotoxicity under glutathione (GSH)-depleted conditions after pretreatment with buthionine sulfoximine, which corresponded to an increase of intracellular reactive oxygen species (ROS) in the cells. Pretreatment of GS28 siRNA-transfected cells with p38 chemical inhibitor significantly inhibited cytotoxicity; we also observed that p38 was activated in the cells by immunoblot analysis. We confirmed the role of p38 MAPK in cotransfected cells with GS28 siRNA and p38 siRNA in the cell viability assay, flow cytometry, and immunoblot. Involvement of apoptotic or autophagic processes in the cells was not shown in the cell viability, flow cytometry, and immunoblot analyses. However, pretreatment of the cells with necrostatin-1 completely inhibited $H_2O_2$-induced cytotoxicity, ROS generation, and p38 activation, indicating that the cell death is necroptotic. Collectively these data imply that $H_2O_2$ induces necroptotic cell death in the GS28 siRNA-transfected cells and that the necroptotic signals are mediated by sequential activations in RIP1/p38/ROS. Taken together, these results indicate that GS28 has a protective role in $H_2O_2$-induced necroptosis via inhibition of p38 MAPK in GSH-depleted neuronal cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1303-1310
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• 2005

This study was performed to investigate the effect of Bunsimgieumgagam on the stress due to the maternal separation in rat. In this study, we researched in 'the behavioral observation', 'the changes of body weight', 'quantitative analysis of the number of BrdU-positive cells per section in dentate gyrus of hippocampus', 'free radical scavenging assay' and 'MTT-based cytotoxicity assay of SK-N-SH cell line', in order to figure out the effect on which Bunsimgieumgagam has the increase of neuron in dentate gyrus of hippocampus damaged by the stress due to the maternal separation. In the behavioral Observation, Bunsimgieumgagam was also efficacious against the decline of one's behavior and anorexia derived from the stress by the maternal separation. In the change of body weight, it showed that the Bunsimgieumgagam is effective in the recovery of weight loss caused by heavy stress(p<0.05). Also, Bunsimgieumgagam had an increasing effect, which is similar to a normal state, on DG's neuron in hippocampus (P<0.001). In free radical scavenging assay, Bunsimgieumgagam had a superior free radical scavenging effect. And it showed a significant result with the high cell proliferation effect in MTT-based cytotoxicity assay(P<0.01, p<0.001) This result suggest that Bunsimgieumgagam has an anti-stress effect and a proliferation effect of neuron in dentate gyrus of hippocampus, and it shows the potential of Bunsimgieumgagam in the treatment for the various disorders derived from children's stress.

• Food Science of Animal Resources
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• v.28 no.4
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• pp.431-436
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• 2008

The impact of storage on the neuroprotective effects against $A\beta$-induced cell death and physicochemical characteristics of milk fortified with BF-7 were investigated. The BF-7 milk exerted protection of neuronal cells SK-N-SH from amyloid beta ($A\beta$)-induced neuronal stress. Our results showed that incubation of the cell with pretreated BF-7 milk, significantly attenuated apoptotic stress by $A\beta$, considered in cell morphology and nucleus shape. The general compositions were maintained consistently in BF-7 fortified milk (BF-7 milk). The BF-7 did not make any disturbance on pH and titratable acidity. The color change was not detected, either. Also, any microorganism had not been detected with more than 7 days storage at $4^{\circ}C$. In sensory evaluation study. the average scores of each sensory attribute were quite similar with plain milk. In conclusion, our results strongly indicate that BF-7 characteristics are quite adequate to be included in milk and BF-7 milk is still working well on neuro-protection, result in enforcing our brain and delaying neurodegeneration.