• Journal of Dental Rehabilitation and Applied Science
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• v.25 no.3
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• pp.293-306
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• 2009

In this study, the biological response of fetal rat calvarial cells on alkali- and heat-treated titanium was assessed. The results were as follows; Cell proliferation on alkali- and heat-treated surfaces showed significantly higher level than on the titanium-6aluminum-4vanadium (weight percentage: 6 % aluminum, 4 % vanadium, Ti-6Al-4V) surface (p<0.01). In ELISA analysis, concentration of $IL-1{\beta}$ and IL-6 were raised when the cells were grown to day 7. Pre-treatment with herbimycin, a known tyrosine kinase inhibitor, suppressed the production of IL-6 (p<0.01). In comparison to commercially pure titanium (grade II, cp-Ti) and Ti-6Al-4V alloy, alkali- and heat-treated titanium enhanced alkaline phosphatase activity (p<0.001). In RT-PCR analysis, alkaline phosphatase, bone sialoprotein, receptor activated nuclear factor ligand mRNA expression was increased alkali- and heat-treated titanium. Herbimycin and SB203580, p38 MAPK inhibitor, were repressed of $IL-1{\beta}-induced$ IL-6 mRNA expression. These results suggest that alkali- and heat-treated titanium stimulate osteoblasts differentiation and facilitate bone remodeling.

• Journal of Embryo Transfer
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• v.32 no.3
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• pp.131-138
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• 2017

In most mammals, metaphase II (MII) oocytes having high maturation promoting factor (MPF) activity have been considered as good oocytes and then used for assisted reproductive technologies including somatic cell nuclear transfer (SCNT). Caffeine increases MPF activity in mammalian oocytes by inhibiting p34cdc2 phosphorylation. The objective of this study was to investigate the effects of caffeine treatment during in vitro maturation (IVM) on oocyte maturation and embryonic development after SCNT in pigs. To this end, morphologically good (MGCOCs) and poor oocytes (MPCOCs) based on the thickness of cumulus cell layer were untreated or treated with 2.5 mM caffeine during 22-42, 34-42, or 38-42 h of IVM according to the experimental design. Caffeine treatment for 20 h during 22-42 h of IVM significantly inhibited nuclear maturation compared to no treatment. Blastocyst formation of SCNT embryos was not influenced by the caffeine treatment during 38-42 h of IVM in MGCOCs (41.1-42.1%) but was significantly improved in MPCOCs compared to no treatment (43.4 vs. 30.1%, P<0.05). No significant effects of caffeine treatment was observed in embryo cleavage (78.7-88.0%) and mean cell number in blastocyst (38.7-43.5 cells). The MPF activity of MII oocytes in terms of p34cdc2 kinase activity was not influenced by the caffeine treatment in MGCOCs (160.4 vs. 194.3 pg/ml) but significantly increased in MPCOCs (133.9 vs. 204.8 pg/ml). Our results demonstrate that caffeine treatment during 38-42 h of IVM improves developmental competence of SCNT embryos derived from MPCOCs by influencing cytoplasmic maturation including increased MPF activity in IVM oocytes in pigs.

• Journal of Life Science
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• v.26 no.4
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• pp.475-483
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• 2016

The current study was conducted to evaluate beneficial effects of a new formula (CWC-9) using four traditional Oriental medicinal herbs, Cynanchum wilfordii, Rehmannia glutinosa, Polygala tenuifolia, and Acorus gramineus, on hippocampal cells and memory function. To examine the neuroprotective effects of a new four-herb extract, cell viability, cytotoxicity, and reactive oxygen species (ROS) assays were performed in HT22 cells and behavioral tests (Morris water maze and passive avoidance retention), Western blot, and immunohistochemistry were performed in a mouse model of focal cerebral ischemia. In HT22 hippocampal cells, pretreatment with CWC-9 resulted in significantly reduced glutamate-induced cell death with suppression of ROS accumulation caused by glutamate. In a mouse model of focal cerebral ischemia, we observed significant improvement of spatial and short-term memory function by treatment with CWC-9. Phosphorylated p38 mitogen-activated protein kinases (MAPK) in hippocampus of ischemic mice were decreased by treatment with CWC-9, but phosphorylated phosphatidylinositol-3 kinase (PI3K) and cAMP response element binding protein (CREB) were significantly enhanced. By immunohistochemical analysis, we confirmed higher expression of phosphorylation of CREB in the hippocampal neurons of CWC-9 treated mice. These results suggest that new multi-herb formula CWC-9 mainly exerted beneficial effects on cognitive function through regulation of neuro-protective signaling pathways associated with CREB.

• Nutrition Research and Practice
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• v.8 no.5
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• pp.501-508
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• 2014

BACKGROUND/OBJECTIVES: Rubus Coreanus Miquel (RCM), used as a traditional Korean medicine, reduces chronic inflammatory diseases such as cancer and rheumatoid arthritis. However, its mechanism has not been elucidated. In this study, we examine the anti-inflammatory effects of RCM and their possible mechanisms using RAW 264.7 cells. MATERIALS/METHODS: Unripe RCM ethanol extract (UE), unripe RCM water extract (UH), ripe RCM ethanol extract (RE), and ripe RCM water extract (RH) were prepared. Inflammatory response was induced with LPS treatment, and expression of pro-inflammatory mediators (iNOS, COX-2, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6) and NO and $PGE_2$ productions were assessed. To determine the anti-inflammatory mechanism of RCM, we measured NF-${\kappa}B$ and MAPK activities. RESULTS: UE and UH treatment significantly reduced NF-${\kappa}B$ activation and JNK and p38 phosphorylation and reduced transcriptional activities decreased iNOS, COX-2, and pro-inflammatory cytokines expressions, and NO and $PGE_2$ productions. RE and RH treatments reduced IL-$1{\beta}$ and IL-6 expressions through suppressions of JNK and p38 phosphorylation. CONCLUSIONS: In this study, we showed that RCM had anti-inflammatory effects by suppression of pro-inflammatory mediator expressions. Especially, unripe RCM showed strong anti-inflammatory effects through suppression of NF-${\kappa}B$ and MAPK activation. These findings suggest that unripe RCM might be used as a potential functional material to reduce chronic inflammatory responses.

• Journal of Life Science
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• v.23 no.5
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• pp.650-656
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• 2013

Endothelial protein C receptor (EPCR) plays a pivotal role in augmenting Protein C activation through the thrombin-thrombomodulin complex. EPCR activity is markedly changed by ectodomain cleavage and released as the soluble protein (sEPCR). EPCR shedding is mediated by tumor necrosis factor-${\alpha}$ converting enzyme (TACE). Lycopene found in tomatoes and tomato products has anti-oxidant, anti- cancer and anti-inflammatory effects. However, little is known about the effects of lycopene on EPCR shedding. We investigated this issue by monitoring the effects of lycopene on the phorbol-12-myristate 13-acetate (PMA), tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$ and on the cecal ligation and puncture (CLP)-mediated EPCR shedding. Data showed that lycopene potently inhibited the PMA, TNF-${\alpha}$, IL-$1{\beta}$ and CLP-induced EPCR shedding by suppressing TACE expression. Furthermore, lycopene reduced PMA-stimulated phosphorylation of p38, extracellular regulated kinases (ERK) 1/2 and c-Jun N-terminal kinase (JNK). Given these results, lycopene should be viewed as a candidate therapeutic agent for the treatment of various severe vascular inflammatory diseases via inhibition of the EPCR shedding.

• Journal of Applied Biological Chemistry
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• v.61 no.4
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• pp.417-421
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• 2018

Ultraviolet rays are electromagnetic waves with a shorter wavelength than visible light, and ultraviolet rays that pass through the ozone layer are the main cause of skin aging. Chronic exposure of skin tissue to ultraviolet light activates the Mitogen-activated Protein Kinases (MAPKs) signaling pathways in human keratinocytes, resulting in increased production of matrix metalloproteinases (MMPs). In this study, we investigated the herbal extracts from Jeju Island on the anti-aging effect in human keratinocytes (HaCaTs) by ultraviolet stimulation. We examined that herb extract from Jeju Island were decreased in anti-aging activity on measuring the level of MMP-1 gene and protein expression in ultraviolet-induced keratinocytes. As a result, it was confirmed that Thymus quinquecostatus extract (TQE) significantly reduced the expression of MMP-1 in a dose-dependent manner by UV irradiated HaCaTs. According to our data, TQE significantly attenuated UV-induced phosphorylation of the MAPKs signaling elements ERK1/2, JNK1/2 and p38 proteins. These results suggest that the MAPKs pathway may contribute to the inhibitory effect of TQE on UV-induced MMP-1 production in human keratinocytes. Our results suggest that TQE may be a protective agent against skin aging by preventing UV-induced MMP-1 production.

• ALGAE
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• v.29 no.4
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• pp.343-353
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• 2014

Despite the extensive literature on marine algae over the past few decades, a paucity of published research and studies exists on red algae. The purpose of this study was to evaluate the potential therapeutic properties of the ethanol extract of the red alga Callophyllis japonica against lipopolysaccharide (LPS)-stimulated macrophage inflammation. The C. japonica extract (CJE) significantly inhibited the nitric oxide (NO) production and the induced dose-dependent reduction of the protein and mRNA levels of inducible nitric oxide synthase and cyclooxygenase-2. Additionally, the CJE reduced the mRNA levels of inflammatory cytokines, including tumor necrosis factor-${\alpha}$, interleukin (IL)-$1{\beta}$, and IL-6. We investigated the mechanism by which the CJE inhibits NO by examining the level of mitogen-activated protein kinases (MAPKs) activation, which is an inflammation-induced signaling pathway in macrophages. The CJE significantly suppressed the LPS-induced phosphorylation of c-Jun N-terminal kinase, extracellular signal-regulated kinase and p38 MAPK. Taken together, the results of this study demonstrate that the CJE inhibits LPS-induced inflammation by blocking the MAPK pathway in macrophages.

• BMB Reports
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• v.45 no.6
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• pp.354-359
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• 2012

We examined that the protective effects of ANX1 on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in animal models using a Tat-ANX1 protein. Topical application of the Tat-ANX1 protein markedly inhibited TPA-induced ear edema and expression levels of cyclooxygenase-2 (COX-2) as well as pro-inflammatory cytokines such as interleukin-1 beta (IL-$1{\beta}$), IL-6, and tumor necrosis factor-alpha (TNF-${\alpha}$). Also, application of Tat-ANX1 protein significantly inhibited nuclear translocation of nuclear factor-kappa B (NF-${\kappa}B$) and phosphorylation of p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) in TPA-treated mice ears. The results indicate that Tat-ANX1 protein inhibits the inflammatory response by blocking NF-${\kappa}B$ and MAPK activation in TPA-induced mice ears. Therefore, the Tat-ANX1 protein may be useful as a therapeutic agent against inflammatory skin diseases.

• Microbiology and Biotechnology Letters
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• v.44 no.4
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• pp.442-451
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• 2016

The aim of this study was to investigate the anti-inflammatory effect of Sargassum miyabei Yendo ethanol extract (SMYEE) using RAW 264.7 cells and croton oil-induced Balb/c mice. SMYEE inhibited the production of pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor $(TNF)-{\alpha}$, and $IL-1{\beta}$] and nitric oxide in lipopolysaccharide (LPS)-induced inflammatory response. In addition, SMYEE suppressed the expression of inducible nitric oxide, cyclooxygenase-2, and nuclear factor-kappa B. Further, SMYEE inhibited the expression of mitogen-activated protein kinases (MAPKs), such as extra cellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase. In ear edema test, edema formation in the SMYEE treatment was lower than that in the positive control and was similar to that in the prednisolone treatment group. Photomicrographs of mice ear tissue showed a reduction in dermal thickness and number of infiltrated mast cells. Therefore, our results indicate that SMYEE exerts an anti-inflammatory effect via inhibition of nuclear factor ${NF}-{\kappa}B$ and MAPK activation and can be used as a natural source of anti-inflammatory compounds.

• Natural Product Sciences
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• v.18 no.1
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• pp.60-66
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• 2012

Human skin is the first line of defense for the protection of the internal organs of the body from different stimuli. Ultraviolet B (UVB) irradiation induces skin damage and inflammation through the secretion of various cytokines, which are immune regulators produced by cells. To prevent the initiation of skin inflammation, keratinocytes that have been irreversibly damaged by radiation must be removed through the apoptotic mechanism. Ixeris dentata (family: Asteraceae) is a perennial medicinal herb indigenous to Korea. It has been used in Korea, China, and Japan to treat in digestion, pneumonia, diabetes, hepatitis, and tumors. To gain insight into the anti-inflammatory effects of I. dentata, we examined its influence on UVB-induced pro-inflammatory cytokine production in human keratinocytes (HaCaT cells), by observing cells that were stimulated with UVB in the presence or absence of I. dentata. In the present study, pro-inflammatory cytokine production was determined by performing enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and western blot analysis to measure the activation of mitogen-activated protein kinase (MAPKs). I. dentata inhibited UVBinduced production of the pro-inflammatory cytokine interleukin (IL)-6 in a dose-dependent manner. Further, I. dentata inhibited the UVB-induced expression of cyclooxygenase (COX)-2. Furthermore, I. dentata inhibited the phosphorylation of c-Jun NH2-terminal kinase and p38 MAPKs, suggesting that it inhibits the secretion of the pro-inflammatory cytokines IL-6 and IL-8, and COX-2 expression, by blocking MAPK phosphorylation. These results suggest that I. dentate can potentially protect against UVB-induced skin inflammation.