• Proceedings of the Korean Environmental Sciences Society Conference
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• 2020.10a
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• pp.218-218
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• 2020

Astaxanthin, a natural antioxidant carotenoid, has been thought to provide health benefits by decreasing the risk of oxidative stress?related diseases. In the present study, we investigated the effect of an astaxanthin during the autophagic cell death induced by bisphenol A (BPA) which is known major environmental pollutants. We found that astaxanthin significantly blocked the autophagic cell death via inhibition of intracellular Reactive Oxygen Species (ROS) in normal human dermal fibroblasts. Astaxanthin significantly inhibited the phosphorylation mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) responsible for the expression of LC3-II and Beclin-1 in BPA-treated normal human dermal fibroblasts. We suggest that astaxanthin blocks autophagic cell death induced by BPA via the inhibition of ROS-mediated signaling events in human dermal fibroblasts.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.476-484
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• 2018

Background: Korean Red Ginseng (steamed and dried white ginseng, Panax ginseng Meyer) is well known for enhancing vital energy and immune capacity and for inhibiting cancer cell growth. Some clinical studies also demonstrated a therapeutic potential of ginseng extract for treating lung inflammatory disorders. This study was conducted to establish the therapeutic potential of ginseng saponins on the lung inflammatory response. Methods: From Korean Red Ginseng, 11 ginsenosides (Rb1, Rb2, Rb3, Rc, Rd, Re, Rf, Rg1, Rg2, Rg3, and Rh2) were isolated. Their inhibitory potential and action mechanism were evaluated using a mouse model of lung inflammation, acute lung injury induced by intranasal lipopolysaccharide administration. Their anti-inflammatory activities were also examined in lung epithelial cell line (A549) and alveolar macrophage (MH-S). Results: All ginsenosides orally administered at 20 mg/kg showed 11.5-51.6% reduction of total cell numbers in bronchoalveolar lavage fluid (BALF). Among the ginsenosides, Rc, Re, Rg1, and Rh2 exhibited significant inhibitory action by reducing total cell numbers in the BALF by 34.1-51.6% (n = 5). Particularly, Re showed strong and comparable inhibitory potency with that of dexamethasone, as judged by the number of infiltrated cells and histological observations. Re treatment clearly inhibited the activation of mitogen-activated protein kinases, nuclear factor-${\kappa}B$, and the c-Fos component in the lung tissue (n = 3). Conclusion: Certain ginsenosides inhibit lung inflammatory responses by interrupting these signaling molecules and they are potential therapeutics for inflammatory lung diseases.

• KSBB Journal
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• v.28 no.6
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• pp.415-422
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• 2013

Gamma irradiation (${\gamma}IR$) is widely used for radiotherapy as a treatment of cancer cells although it has a risk to damage normal cells. Inflammation is regarded as one of side effects of ${\gamma}IR$ while the effect of low dose of ${\gamma}IR$ on inflammation has not been researched well. Here, we investigated the inflammatory responses of low dose of ${\gamma}IR$ on murine spleen cells. It was evaluated if ${\gamma}IR$ affected the mitogen-induced lymphocyte proliferation, the regulation of various inflammatory cytokines (IFN-${\gamma}$, IL-2, IL-17, IL-4, IL-10), and the involvement of Ikaros and MAPK/NF-${\kappa}B$ medicated mechanism. Exposure of $^{137}Cs-{\gamma}IR$ below 2 Gy decreased the lymphocytes proliferative response to mitogens (LPS, ConA) except at the lowest dose, 0.05 Gy. IL-17, IL-2 and IL-4 mRNA increased at 0.5 and 2 Gy, but not altered at 0.05 Gy. IL-10, anti-inflammatory cytokine, increased only at 0.05 Gy. In regard to intracellular signaling, p-JNK, p-p38 and p-$I{\kappa}B{\alpha}$ were not changed, whereas the activation of ERK and Ikaros increased at the lowest dose. These results suggest that exposure of ${\gamma}IR$ less than 0.5 Gy (or below 0.05 Gy) has beneficial effects as a radiation hormesis on immune function.

• International Journal of Oral Biology
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• v.38 no.2
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• pp.67-72
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• 2013

This study examined the anti-osteoclastogenic effects of baicalin on receptor activator of NF-${\kappa}$B ligand (RANKL)-induced RAW264.7 cells. Baicalin is a flavonoid that is produced by Scutellaria baicalensis and is known to have multiple biological properties, including antibacterial, anti-inflammatory and analgesic effects. The effects of baicalin on osteoclasts were examined by measuring 1) cell viability; 2) the formation of tartrate-resistant acid phosphatase (TRAP) (+) multinucleated cells; 3) RANK/RANKL signaling pathways and 4) mRNA levels of osteoclast-associated genes. Baicalin inhibited the formation of RANKL-stimulated TRAP (+) multinucleated cells and also suppressed the RANKL-stimulated activation of p-38, ERK, cSrc and AKT signaling. Baicalin also inhibited the RANKL-stimulated degradation of $I{\kappa}B$ in RAW264.7 cells. In addition, the RANKL-stimulated induction of NFATc1 transcription factors was found to be abrogated by this flavonoid. Baicalin was further found to decrease the mRNA expression of osteoclast-associated genes, including carbonic anhydrase II, TRAP and cathepsin K in the RAW264.7 cells. Our data thus demonstrate that baicalin inhibits osteoclastogenesis by inhibiting the RANKL-induced activation of signaling molecules and transcription factors in osteoclast precursors.

• Journal of Microbiology and Biotechnology
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• v.30 no.12
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• pp.1927-1936
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• 2020

Tunicates are known to contain biologically active materials and one species in particular, the sea peach (Halocynthia aurantium), has not been thoroughly studied. In this study we aimed to analyze the fatty acids profile of the H. aurantium body wall and its immunomodulatory effects on RAW264.7 macrophage-like cells. The fatty acids were classified into three categories: saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs). Omega-3 fatty acid content, including EPA and DHA, was higher than omega-6 fatty acids. H. aurantium body wall fatty acids exhibited enhanced immune response and anti-inflammatory effects on RAW264.7 macrophage-like cells. Under normal conditions, fatty acids significantly increase nitric oxide (NO) and PGE2 production in a dose-dependent manner, thereby improving the immune response. On the other hand, in LPS-treated RAW264.7 cells, fatty acids significantly decreased nitric oxide (NO) and PGE2 production in a dose-dependent manner, thereby enhancing anti-inflammatory effects. Fatty acids transcriptionally control the expression of the immune-associated genes, iNOS, IL-1β, IL-6, COX-2, and TNF-α, via the MAPK and NF-κB signaling cascades in RAW264.7 cells. However, in LPS-stimulated RAW264.7 cells, H. aurantium body wall fatty acids significantly inhibited expression of inflammatory cytokine; similarly, production of COX-2 and PGE2 was inhibited. The results of our present study provide insight into the immune-improving and anti-inflammatory effects of H. aurantium body wall fatty acids on macrophages. In addition, our study demonstrates that H. aurantium body wall is a potential source of immune regulatory components.

• Microbiology and Biotechnology Letters
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• v.50 no.1
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• pp.22-30
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• 2022

Haliotis discus hannai called abalone, is the valuable marine mollusks and the by-products of abalone processing are viscera. Brownish abalone male viscera (AMV), which have not been reported as having anti-inflammatory effects, was extracted with acetone and fractionated by different six acetone/hexane ratios (0, 10, 20, 30, 40, and 100%) using a silica column via in vitro ABTS and DPPH radical and nitric oxide (NO) production assay-guided fractionation. Among the fractions, the acetone/hexane ratio 40%, A40 exhibited the most potent radical scavenging activities and inhibition of lipopolysaccharide (LPS)-induced NO production without cytotoxicity. A40 inhibited LPS-induced intracellular reactive oxygen species (ROS) production in a dose-dependent manner. Western blot analysis revealed that A40 down-regulated the activation of NF-κB, MAPK (ERK 1/2, p-38, and JNK), and inflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2. Moreover, this fraction inhibited the generation of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. These results suggested that AMV containing A40 with anti-inflammatory and anti-oxidantive effects, is the effective therapeutic and functional material for treating inflammatory disorders.

• Molecules and Cells
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• v.45 no.10
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• pp.749-760
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• 2022

Osteoclast generation from monocyte/macrophage lineage precursor cells needs to be tightly regulated to maintain bone homeostasis and is frequently over-activated in inflammatory conditions. PARK2, a protein associated with Parkinson's disease, plays an important role in mitophagy via its ubiquitin ligase function. In this study, we investigated whether PARK2 is involved in osteoclastogenesis. PARK2 expression was found to be increased during the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. PARK2 gene silencing with siRNA significantly reduced osteoclastogenesis induced by RANKL, LPS (lipopolysaccharide), TNFα (tumor necrosis factor α), and IL-1β (interleukin-1β). On the other hand, overexpression of PARK2 promoted osteoclastogenesis. This regulation of osteoclastogenesis by PARK2 was mediated by IKK (inhibitory κB kinase) and NF-κB activation while MAPK (mitogen-activated protein kinases) activation was not involved. Additionally, administration of PARK2 siRNA significantly reduced osteoclastogenesis and bone loss in an in vivo model of inflammatory bone erosion. Taken together, this study establishes a novel role for PARK2 as a positive regulator in osteoclast differentiation and inflammatory bone destruction.

• Molecules and Cells
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• v.26 no.6
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• pp.583-589
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• 2008

In the present study, we investigated whether rosmarinic acid, which has been suggested to exhibit anti-inflammatory properties, can suppress the expressions of monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-$1{\alpha}$ ($MIP-1{\alpha}$) via the MAPK pathway in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) in the presence of GM-CSF and IL-4 in media. The effects of rosmarinic acid were investigated in BMDCs with respect to the following; cytotoxicity, surface molecule expression, dextran-FITC uptake, cell migration, chemokine gene expression, and the MAPK signaling pathway. Rosmarinic acid was found to significantly inhibit the expressions of CD80, CD86, MHC class I, and MHC class II in LPS-stimulated mature BMDCs, and rosmarinic acid-treated BMDCs were found to be highly efficient with regards to antigen capture via mannose receptor-mediated endocytosis. In addition, rosmarinic acid reduced cell migration by inducing the expression of a specific chemokine receptor on LPS-induced mature BMDCs. Rosmarinic acid also significantly reduced the expressions of MCP-1 and $MIP-1{\alpha}$ induced by LPS in BMDCs and inhibited LPS-induced activation of MAPK and the nuclear translocation of $NF-{\kappa}B$. These findings broaden current perspectives concerning our understanding of the immunopharmacological functions of rosmarinic acid, and have ramifications that concern the development of therapeutic drugs for the treatment of DC-related acute and chronic diseases.

• Journal of Life Science
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• v.31 no.10
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• pp.898-904
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• 2021

Locusta migratoria is a widespread locust species in many parts of the world and is considered an alternative source for the production of protein for value-added ingredients. We previously identified putative antimicrobial peptides derived from L. migratoria through an in silico analysis of its transcriptome. However, its anti-inflammatory effect has not been studied. In this study, we investigated the anti-inflammatory activities of the antimicrobial peptide locustacin (KTHILSFFPSFLPLFLKK-NH₂) derived from L. migratoria on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Locustacin (50, 100, and 200 ㎍/ml) significantly reduced the production of nitric oxide (NO) in LPS-stimulated macrophages without any cytotoxicity. Locustacin also inhibited the mRNA and protein expression of pro-inflammatory mediators, such as inducible NO synthase and cyclooxygenase-2, in contrast to the presence of LPS alone. Locustacin decreased the release of LPS-induced pro-inflammatory cytokines, including interleukin (IL)-6 and IL-1β, and their gene expression in a dose-dependent manner. Furthermore, locustacin (100 and/or 200 ㎍/ml) inhibited phosphorylation levels of extracellular signal regulated kinase, p38, and c-Jun N-terminal kinase. Locustacin also suppressed the degradation of inhibitory kappa B alpha, which was considered to be an inhibitor of nuclear factor kappa B (NF-κB). Collectively, these results demonstrate that locustacin can exert anti-inflammatory effects through the inhibition of mitogen-activated protein kinase (MAPK) phosphorylation, activation of NF-κB, and downstream inflammatory mediators in LPS-stimulated macrophage cells.

• Journal of The Korean Society of Integrative Medicine
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• v.8 no.4
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• pp.163-169
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• 2020

Purpose : This study aimed to investigate the anti-allergic effect of Persicaria perfoliata water extract (PPWE) on IgE stimulated rat basophilic leukemia (RBL-2H3) cell line. Methods : P. perfoliata (L.) H. Gross has been used in traditional medicine as an anti-allergic agent, antipyretic, and diuretic and for respiratory disorders. To analyze the anti-allergic activity of PPWE, release of β-hexosaminidase in RBL-2H3 cells was estimated by enzyme linked immunosorbant assay (ELISA). Also, the cytotoxic effect of PPWE was identified by WST assay, and nuclear factor (NF)-κB and its upstream signaling molecules were assessed by western blot analysis. Results : PPWE treatment significantly attenuated β-hexosaminidase release in a dose dependent manner without any cytotoxicity. PPWE inhibited β-hexosaminidase activity by 38.4±1.2, 36.6±0.6, 32.5±2.2 and 26.5±1.2 at 500, 250, 100, and 50 ㎍/㎖ of PPWE, respectively, compared with the control group. In addition, an analysis of the expression level of NF-κB, an inflammation transcription factor, in RBL-2H3 cells upon IgE stimulation provided reults consistent with the results of β-hexosaminidase release. The phosphorylated status of upstream signaling molecules for transcription factor, mitogen activated protein kinases (MAPKs), was also analyzed. The results showed that PPWE treatment dose-dependently inhibited phosphorylation of extracellular regulatory kinase (ERK) and c-Jun N-terminal kinase (JNK). These results show that PPWE had a strong IgE-mediated degranulation inhibitory effect on RBL-2H3 cells. Conclusion : P. perfoliata ameliorated IgE-mediated allergic reaction via the modulation of MAPK and NF-κB signaling pathway in RBL-2H3 cells. These results indicate that P. perfoliata could be a potential candidate for a treatment strategy against various allergic disorders.