• The Korean Journal of Physiology and Pharmacology
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• 제8권5호
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• pp.237-243
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• 2004

Glial cells are activated in neuropathy and play a key role in hyperalgesia and allodynia. This study was performed to determine whether minocycline could attenuate heat hyperalgesia and mechanical allodynia, and how glial cell activation and nuclear factor kappa B (NF-kappaB) were regulated by minocycline in a model of chronic constriction of sciatic nerve (CCl). When minocycline (50 mg/kg, oral) was daily administered from 1 day before to 9 days after ligation, heat hyperalgesia and mechanical allodynia were attenuated. Furthermore, when minocycline treatment was initiated 1 or 3 days after ligation, attenuation of the hypersensitive behavior was still robust. However, the effect of attenuation was less when minocycline was started from day 5. In order to elucidate the mechanism of pain attenuation by minocycline, we examined the changes of glia and NF-kappaB, and found that attenuated hyperalgesia and allodynia by minocycline was accompanied by reduced microglial activation. Furthermore, the number of NF-kappaB immunoreactive cells increased after CCI treatment and this increase was attenuated by minocycline. We also observed translocation of NF-kappaB into the nuclei of activated glial cells. These results suggest that minocycline inhibits activation of glial cells and NF-kappaB, thereby attenuating the development of behavioral hypersensitivity to stimuli.

• Preventive Nutrition and Food Science
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• 제4권3호
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• pp.209-214
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• 1999

In this study, the effectof ethanol and acetaldehyde on DNA binding activities of NF-$textsc{k}$B and AP-1 were evaluated in C6 rat glial cells. Both NF-$textsc{k}$B and AP-1 are important transcription factors for the expression of various cytokines in glial cells. Our data showed that neither ethanol nor acetaldehyde induced conspicuous cell death of C6 cells at clinically realistic concentrations. When the DNA binding activities of nuclear NF-$textsc{k}$B and AP-1 were estimated using electrophoretic mobility shift assay (EMSA), ethanol(0.3%) or acetaldehyde(1mM) induced transient activation of these transcription factors, which attained peak levels at 4~8 hours and declined to basal levels at 12 hours after treatement . The supershift analysis showed that the increased activities of NF-$textsc{k}$B in ethanol/acetaldehyde-treated C6 cells were due to the preferential induction of p65/p50 heterodimer complex. The DNA binding activities of these transcriptional factors decreased below basal levels when cells were cultured with either ethanol or acetaldehyde for 24 hours, and showed the inhibitory effect of chronic ehtanol /acetaldehyde treatment on the activities of these transsriptional factors. Our data indicate that either ethanol or acetaldehyde can induce functional changes of glial cells throught bi-directional modulation of NF-$textsc{k}$B and AP-1 DNA binding activities.

• Nutrition Research and Practice
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• 제9권2호
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• pp.123-128
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• 2015

BACKGROUND/OBJECTIVES: Natural products or active components with a protective effect against oxidative stress have attracted significant attention for prevention and treatment of degenerative disease. Oligonol is a low molecular weight polyphenol containing catechin-type monomers and oligomers derived from Litchi chinensis Sonn. We investigated the protective effect and its related mechanism of oligonol against oxidative stress. MATERIALS/METHODS: Oxidative stress in C6 glial cells was induced by hydrogen peroxide ($H_2O_2$) and the protective effects of oligonol on cell viability, nitric oxide (NO) and reactive oxygen species (ROS) synthesis, and mRNA expression related to oxidative stress were determined. RESULTS: Treatment with oligonol inhibited NO and ROS formation under cellular oxidative stress in C6 glial cells. In addition, it recovered cell viability in a dose dependent-manner. Treatment with oligonol also resulted in down-regulated mRNA expression related to oxidative stress, nuclear factor kappa-B (NF-${\kappa}B$) p65, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), compared with the control group treated with $H_2O_2$. In particular, expression of NF-${\kappa}B$ p65, COX-2, and iNOS was effectively reduced to the normal level by treatment with $10{\mu}g/mL$ and $25{\mu}g/mL$ of oligonol. CONCLUSIONS: These results indicate that oligonol has protective activity against oxidative stress-induced inflammation. Oligonol might be a promising agent for treatment of degenerative diseases through inhibition of ROS formation and NF-${\kappa}B$ pathway gene expression.

• 농업과학연구
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• 제45권3호
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• pp.509-519
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• 2018

This study was investigated the anti-oxidant property and neuro-protective effect of Cirsium japonicum var. maackii (CJM) against oxidative stress in hydrogen peroxide ($H_2O_2$)-induced C6 glial cells. We measured the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, hydroxyl radical (${\cdot}OH$), and superoxide ($O_2{^-}$) radical scavenging activities of an ethanol extract and four fractions [n-Butanol, ethyl acetate (EtOAc), $CHCl_3$, and n-Hexane] from CJM. The results of this study show that the extract and all fractions from CJM had a dose-dependent DPPH radical scavenging activity. In particular, the EtOAc fraction exhibited the strongest scavenging effect with 88.23% at a concentration of $500{\mu}g/mL$. In addition, the EtOAc fraction from CJM also effectively scavenged ${\cdot}OH$ radicals and $O_2{^-}$ radicals, compared to other extract and fractions. In C6 glial cells, $H_2O_2$ markedly decreased the cell viability as well as increased lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) production. However, the EtOAc fraction of CJM attenuated the cellular damage from the oxidative stress by elevating the cell viability and inhibiting the LDH release and ROS over-production compared with the $H_2O_2$-treated control group. Our findings indicate that the EtOAc fraction from CJM has antioxidant effect and neuro-protective effect against oxidative stress, suggesting that it can be used as a natural antioxidant and therapeutic agent for the prevention of neurodegenerative disorders.

• Journal of Ginseng Research
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• 제48권5호
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• pp.464-473
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• 2024

Background: The effects of individual panaxadiol saponin and panaxatriol saponin on rodent models of Parkinson's disease (PD) have been recognized. However, it is not clear whether purified total ginsenosides as an entirety has effect against PD in rat model. This study compared the protective effects of a purified panaxadiol saponin fraction (PDSF), a purified panaxatriol saponin fraction (PTSF), and their mixtures against the rotenone (ROT)-induced PD in rats. Methods: Potential effects of PDSF, PTSF, and their mixtures against motor dysfunction and impairments of nigrostriatal dopaminergic neurons (DN), blood-brain barrier (BBB), cerebrovascular endothelial cells (CEC), and glial cells were measured in the models of ROT-induced PD rats and cell damage. Pro-inflammatory NF-kB p65 (p65) activation was localized in DN and other cells in the striatum. Results: PDSF and PTSF had a dose-dependent effect against motor dysfunction with a larger effective dose range for PDSF. PDSF protected CEC, glial cells, and DN in models of PD rats and cell damage, while PTSF had no such protections. Chronic ROT exposure potently activated p65 in CEC with enhanced pro-inflammatory and decreased anti-inflammatory factors and impaired BBB in the striatum, PDSF almost completely blocked the ROT-induced p65 activation and maintained both anti- and pro-inflammatory factors at normal levels and BBB integrity, but PTSF aggravated the p65 activation with impaired BBB. Furthermore, PTSF nullified all the effects of PDSF when they were co-administrated. Conclusion: PDSF had significant protective effect against the ROT-induced PD in rats by protecting CEC, glial cells, and DN, likely through inhibiting NF-κB p65 in CEC from triggering neuroinflammation, and also directly protecting glial cells and neurons against ROT-induced toxicity. PDSF has great potential for preventing and treating PD.

• Parasites, Hosts and Diseases
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• 제52권6호
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• pp.613-619
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• 2014

Neospora caninum (Apicomplexa; Sarcocystidae) is a protozoan that causes abortion in cattle, horses, sheep, and dogs as well as neurological and dermatological diseases in dogs. In the central nervous system of dogs infected with N. caninum, cysts were detected that exhibited gliosis and meningitis. Flavonoids are polyphenolic compounds that exhibit antibacterial, antiparasitic, antifungal, and antiviral properties. In this study, we investigated the effects of flavonoids in a well-established in vitro model of N. caninum infection in glial cell cultures. Glial cells were treated individually with 10 different flavonoids, and a subset of cultures was also infected with the NC-1 strain of N. caninum. All of the flavonoids tested induced an increase in the metabolism of glial cells and many of them increased nitrite levels in cultures infected with NC-1 compared to controls and uninfected cultures. Among the flavonoids tested, 3',4'-dihydroxyflavone, 3',4',5,7-tetrahydroxyflavone (luteolin), and 3,3',4',5,6-pentahydroxyflavone (quercetin), also inhibited parasitophorous vacuole formation. Taken together, our findings show that flavonoids modulate glial cell responses, increase NO secretion, and interfere with N. caninum infection and proliferation.

• 생약학회지
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• 제47권3호
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• pp.251-257
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• 2016

In this study, the radical scavenging activity and protective effect of ethanol extract from leaf of Engelhardtia chrysolepis HANCE (ECE) against oxidative stress were investigated under in vitro and cellular system. ECE showed strong radical scavenging activities in 1,1-diphenyl-2-picrylhydrazyl, hydroxyl(${\cdot}OH$) and nitric oxide(NO) radical as a concentration-dependent manner. Particularly, strong scavenging activity against the ${\cdot}OH$ and NO radical were observed with the $IC_{50}$ value of $1.30{\mu}g/ml$ and $12.61{\mu}g/ml$, respectively. Furthermore, the cellular oxidative stress was induced by amyloid beta($A{\beta}_{25-35}$) in C6 glial cells. The treatment of $A{\beta}_{25-35}$ to C6 glial cells generated high levels of reactive oxygen species(ROS) and declined cell viability. However, production of ROS was decreased by the treatment of ECE. In addition, the cell viability was significantly increased at each concentration(10, 25, $50{\mu}g/ml$) as dose-dependent manner. The Alzheimer's disease-related protein expressions in $A{\beta}_{25-35}$-treated C6 glial cells were analyzed. The ECE treatment inhibited expression of amyloid precursor protein(APP), C-terminal fragment-${\beta}(CTF-{\beta})$, ${\beta}$-site APP cleaving enzyme(BACE), phosphorylated tau(p-tau) proteins in C6 glial cells induced by $A{\beta}_{25-35}$. The present study indicated that ECE has strong radical scavenging activity and neuroprotective effect through attenuating oxidative stress.

• 동의생리병리학회지
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• 제23권2호
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• pp.374-380
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• 2009

Samryungbaikchul-san(SRBCS) has been used in oriental medicine for the treatments of gastrointestinal and neurological disorders. Here, potential protective function of SRBCS was investigated in neural tissues in Alzheimer's disease(AD) mouse model. In primary cultured cells from the spinal cord of newborn rats, treatment of ${\beta}$-amyloid peptide elevated cell counts positive to glial fibrillary acidic protein(GFAP) or caspase 3 immunoreactivity, but the co-treatment of SRBCS reduced positive cell counts. In vivo administration of scopolamine, an inhibitor of muscarinic receptor, resulted in increases in the number of glial fibrillary acidic protein(GFAP) and caspase 3-positive cells in hippocampal subfields, which was then decreased by the treatment of SRBCS or acetylcholinesterase inhibitor galathamine. The present data suggest that SRBCS may play a protective role in damaged neural tissues caused by scopolamine treatments in mice.

• 대한의생명과학회지
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• 제12권3호
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• pp.275-279
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• 2006

It is demonstrated that cadmium has cytotoxic effect on glial cells, oxygen radicals are involved in cadmium-induced cytotoxicity. However, the toxic mechanism of cadmium is left unknown so far. The purpose of this study was to examine the cytotoxicity of $CdCl_2$ on $C_6$ glioma cells. The cytotoxicy was measured by cell viability via XTT assay in $C_6$ glioma cells. Colorimetric assay such as XTT assay is regarded as a very sensitive screening method for the determination of the cell viability on a lots of chemicals. In this study, $CdCl_2$ decreased cell viability according to the dose- and time dependent manners after $C_6$ glioma cells were treated with various concentrations of $CdCl_2$ for 48 hours. $IC_{90}\;and\;IC_{50}$ values for XTT assay was determined at $5{\mu}M\;and\;55{\mu}M$ of $CdCl_2$, respectively. These results suggest that $CdCl_2$ has highly cytotoxic effect on $C_6$glioma cells by the decrease of cell viability.

• BMB Reports
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• 제53권12호
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• pp.646-651
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• 2020

Bone resorption is linked to bone formation via temporal and spatial coupling within the remodeling cycle. Several lines of evidence point to the critical role of coupling factors derived from pre-osteoclasts (POCs) during the regulation of bone marrow-derived mesenchymal stem cells (BMMSCs). However, the role of glial cell-derived neurotrophic factor (GDNF) in BMMSCs is not completely understood. Herein, we demonstrate the role of POC-derived GDNF in regulating the migration and osteogenic differentiation of BMMSCs. RNA sequencing revealed GDNF upregulation in POCs compared with monocytes/macrophages. Specifically, BMMSC migration was inhibited by a neutralizing antibody against GDNF in pre-osteoclast-conditioned medium (POC-CM), whereas treatment with a recombinant GDNF enhanced migration and osteogenic differentiation. In addition, POC-CM derived from GDNF knock-downed bone marrow macrophages suppressed BMMSC migration and osteogenic differentiation. SPP86, a small molecule inhibitor, inhibits BMMSC migration and osteogenic differentiation by targeting the receptor tyrosine kinase RET, which is recruited by GDNF into the GFRα1 complex. Overall, this study highlights the role of POC-derived GDNF in BMMSC migration and osteogenic differentiation, suggesting that GDNF regulates bone metabolism.