• Archives of Pharmacal Research
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• v.28 no.2
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• pp.216-219
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• 2005

Wogonin (5,7-dihydroxy-8-methoxyflavone) has been reported to exhibit a variety of biological properties including anti-inflammatory and neuroprotective functions. In this study, biological activities of diverse synthetic wogonin derivatives have been evaluated in two experimental cell culture models. Inhibitory activities of wogonin derivatives on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV2 microglial cells and on hydrogen peroxide ($H_{2}O_2$)-induced neuronal cell death in SH-SY5Y human neuroblastoma were examined. Wogonin derivatives such as WS2 and WS3 showed more potent suppressive activities on LPS-induced NO production and $H_{2}O_2$-induced cytotoxicity than wogonin itself. In addition, thiol substitution played a minor role in enhancing the activities of the derivatives. These findings may contribute to the development of novel anti-inflammatory and neuroprotective agents derived from wogonin.

• Journal of Life Science
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• v.18 no.4
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• pp.542-549
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• 2008

Cisplatin (cis-diamminedichloroplatinum II : CDDP) is the most widely used anticancer drug against a variety of human neoplasms. However, its clinical use is limited by the onset of severe side effects, including ototoxicity and nephrotoxicity. Even though a number of evidences in cytotoxic mechanism of cisplatin have been suggested, the role of pro-inflammatory cytokines in cisplatin cytotoxicity of auditory cells has not yet been demonstrated. Herein our data clearly demonstrated that cisplatin decreased the viability of HEI-OC1 auditory cells, which was inhibited by the addition of neutralizing $anti-TNF-{\alpha}$, $anti-IL-1{\beta}$ and anti-IL-6 antibodies. Consistently, Neutralization with antibodies against pro-inflammatory cytokines ameliorated the cell death and disarrangement of cochlea hair cell layers in the rat primary cochlear explants which were treated with cisplatin. Furthermore, exogeneous supplementation with free radical scavengers, including GSH and NAC, significantly prevented the cytotoxicity of cisplatin in the rat primary cochlea explants. We also observed that $TNF-{\alpha}$ was predominantly expressed in Deiters and Hensen's cells located in hair cell zone of cisplatin-treated cochlear explants. These findings suggest that pro-inflammatory cytokines, including $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6, may play a pivotal role in the pathophysiology of hair cell damages caused by ototoxic drug cisplatin.

• Journal of Animal Reproduction and Biotechnology
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• v.39 no.2
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• pp.145-152
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• 2024

Background: Despite its anticancer activity, cisplatin exhibits severe testicular toxicity when used in chemotherapy. Owing to its wide application in cancer therapy, the reduction of damage to normal tissue is of imminent clinical need. In this study, we evaluated the effects of catechin hydrate, a natural flavon-3-ol phytochemical, on cisplatin-induced testicular injury. Methods: Type 2 mouse spermatogonia (GC-1 spg cells) were treated with 0-100 μM catechin and cisplatin. Cell survival was estimated using a cell proliferation assay and Ki-67 immunostaining. Apoptosis was assessed via flow cytometry with the Dead Cell Apoptosis assay. To determine the antioxidant effects of catechin hydrate, Nrf2 expression was measured using qPCR and CellROX staining. The anti-inflammatory effects were evaluated by analyzing the gene and protein expression levels of iNOS and COX2 using qPCR and immunoblotting. Results: The 100 μM catechin hydrate treatment did not affect healthy GC-1 spg cells but, prevented cisplatin-induced GC-1 spg cell death via the regulation of anti-oxidants and inflammation-related molecules. In addition, the number of apoptotic cells, cleaved-caspase 3 level, and BAX gene expression levels were significantly reduced by catechin hydrate treatment in a cisplatin-induced GC-1 spg cell death model. In addition, antioxidant and anti-inflammatory marker genes, including Nrf2, iNOS, and COX2 were significantly downregulated by catechin hydrate treatment in cisplatintreated GC-1 cells. Conclusions: Our study contributes to the opportunity to reintroduce cisplatin into systemic anticancer treatment, with reduced testicular toxicity and restored fertility.

• The Journal of Korean Medicine
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• v.27 no.4
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• pp.105-115
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• 2006

Fucoidan has been shown to exhibit a host of biological activities, including anti-coagulant, anti-thrombotic, anti-tumourigenic, anti-inflammatory, anti-viral, anti-complementary and neuroprotective effects. In the present study, we attempted to determine the effects of Fucoidan on both apoptosis and cell proliferation in the hippocampal CA1 region and the dentate gyrus of gerbils after the induction of transient global ischemia. This experiment involved the use of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay as well as immunohistochemisty for caspase-3 and 5-bromo-2'-deoxyuridine (BrdU). The monosaccharide composition of the purified Fucoidan which had been extracted from Laminaria religiosa was utilized in this study. The present study clearly induces that apoptotic cell death and cell proliferation in the gerbil's hippocampal regions increased significantly following the induction of transient global ischemia and the results of this study also indicate that Fucoidan exerted a suppressive effect on this observed ischemia-induced increase in apoptosis within the CA1 and dentate gyrus, and also suppressed cell proliferation in the dentate gyrus.

• The Korean Journal of Physiology and Pharmacology
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• v.7 no.6
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• pp.307-310
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• 2003

Kainic acid (KA) is a structural analogue of glutamate that interacts with specific presynaptic and postsynaptic receptors to potentiate the release and excitatory actions of glutamate. Systemic or intracerebroventricular (i.c.v.) administration of KA to experimental animals elicits multifocal seizures with a predominantly limbic localization, and results in neuronal death of cornu ammonia 1 (CA1), reactive gliosis and biochemical changes in the hippocampus and other limbic structures. Several lines of evidence suggest that reactive oxygen species (ROS) play a pivotal role in the pathogenesis of excitotoxic death by KA. Curcumin has been known to possess anti-oxidative and anti-inflammatory activities. In this study, the effects of curcumin on KA induced hippocampal cell death, reactive gliosis and biochemical changes in reactive glia were investigated by immunohistochemical methods. Our data demonstrated that curcumin attenuated KA-induced astroglial and microglial activation although it did not protect KA-induced hippocampal cell death.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.191-191
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• 2002

Inflammatory as well as oxidative tissue damage has been associated with pathophysiology of Alzheimer's disease (AD), and nonsteroidal anti-inflammatory drugs have been shown to retard the progress of AD. In this study, we have investigated the molecular mechanisms underlying oxidative and inflammatory cell death induced by beta-amyloid (Abeta), a neurotoxic peptide associated with senile plaques formed in the brains of patients with AD, in cultured PC12 cells.(omitted)

• Journal of the Society of Cosmetic Scientists of Korea
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• v.31 no.3 s.52
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• pp.219-236
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• 2005

Glycolic acid, an alpha-hydroxy acid derived from fruit and milk sugars, has been commonly used as a cosmetic ingredient since it was known to have photo-protective, anti-inflammatory effects, and anti-oxidant effect in UV-irradiated skin. However, little has been know about the functional role of glycolic acid on UV-induced skin cell proliferation. It was previously found that glycolic acid inhibited UV-induced skin tumor development in hairless mouse. As a possible mechanism of glycolic acid on the UV-induced skin tumor development, the ability of glycolic acid to inhibit the UVB-induced cell growth and possible mechanisms were investigated. Glycolic acid treatment attenuated the UV-induced cell proliferation and apoptotic cell death in the skin. In vitro study, glycolic acid inhibited the UVB-induced cell growth and apoptotic death through inhibiting caspase-3 activity. These results suggest that glycolic acid may exert the Inhibitory effect on the UVB-induced skin tumor development by regulating cell growth and apoptotic cell death.

• IMMUNE NETWORK
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• v.12 no.3
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• pp.104-112
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• 2012

Silica is one of the most abundant compounds found in nature. Immoderate exposure to crystalline silica has been linked to pulmonary disease and crystalline silica has been classified as a Group I carcinogen. Ultrafine (diameter <100 nm) silica particles may have different toxicological properties compared to larger particles. We evaluated the effect of ultrafine silica nanoparticles on mouse bone marrow-derived dendritic cells (BMDC) and murine dendritic cell line, DC2.4. The exposure of dendritic cells (DCs) to ultrafine silica nanoparticles showed a decrease in cell viability and an induction of cell death in size- and concentration-dependent manners. In addition, in order to examine the phenotypic changes of DCs following co-culture with silica nanoparticles, we added each sized-silica nanoparticle along with GM-CSF and IL-4 during and after DC differentiation. Expression of CD11c, a typical DC marker, and multiple surface molecules such as CD54, CD80, CD86, MHC class II, was changed by silica nanoparticles in a size-dependent manner. We also found that silica nanoparticles affect inflammatory response in DCs in vitro and in vivo. Finally, we found that p38 and NF-${\kappa}B$ activation may be critical for the inflammatory response by silica nanoparticles. Our data demonstrate that ultrafine silica nanoparticles have cytotoxic effects on dendritic cells and immune modulation effects in vitro and in vivo.

• BMB Reports
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• v.48 no.3
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• pp.172-177
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• 2015

Upregulation of pro-inflammatory mediators contributes to ${\beta}$-cell destruction and enhanced infiltration of immune cells into pancreatic islets during development of type 1 diabetes mellitus. In this study, we examined the regulatory effects and the mechanisms of action of celastrol against cytotoxicity and pro-inflammatory immune responses in the RINm5F rat pancreatic ${\beta}$-cell line stimulated with a combination of interleukin-1 beta, tumor necrosis factor-alpha, and interferon-${\gamma}$. Celastrol significantly restored cytokine-induced cell death and significantly inhibited cytokine-induced nitric oxide production. In addition, the protective effect of celastrol was correlated with a reduction in pro-inflammatory mediators, such as inducible nitric oxide synthase, cyclooxygenase-2, and CC chemokine ligand 2. Furthermore, celastrol significantly suppressed cytokine-induced signaling cascades leading to nuclear factor kappa B (NF-${\kappa}B$) activation, including $I{\kappa}B$-kinase (IKK) activation, $I{\kappa}B$ degradation, p65 phosphorylation, and p65 DNA binding activity. These results suggest that celastrol may exert its cytoprotective activity by suppressing cytokine-induced expression of pro-inflammatory mediators by inhibiting activation of NF-${\kappa}B$ in RINm5F cells.

• IMMUNE NETWORK
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• v.5 no.1
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• pp.45-49
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• 2005

Background: Inflammation in the brain has known to be associated with the development of a various neurological diseases. The hallmark of neuro-inflammation is the activation of microglia, brain macrophage. Pro-inflammatory compounds including nitric oxide (NO) are the main cause of neuro-degenerative disease such as Alzheimer's disease (AD) which is resulted in cell death. Among those pro-inflammatory compounds, NO contributes to the cell death by directly or indirectly. Methods: In the study, we examined whether ursodeoxycholic acid (UDCA), a non-toxic hydrophilic bile acid, inhibits the NO production by a direct method using Griess reagent and by RT-PCR in the gene expression of inducible nitric oxide synthase (iNOS). In signal transduction, we also examined the NF-${\kappa}B$ (p65/p50), IKK, and I ${\kappa}B$, which are associated with the expression of iNOS gene using western blots. Results: In the present study, we found that UDCA effectively inhibited NO production in BV-2 microglial cell, and NF-${\kappa}B$ activation was reduced by suppressing IKK gene expression and by increasing the I${\kappa}B$ in cytosol comparing those to the positive control LPS. Conclusion: Taken together, these data suggested that UDCA may playa crucial role in inhibiting the NO production and the results imply that UDCA suppresses a cue signal of the microglial activation via stimulators, such as ${\beta}$-amyloid peptides which are known to stimulate microglia in AD pathogenesis.