• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.5
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• pp.494-498
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• 2014

It is well known that Desomodii Herba (DH) has an effect to eliminate dampness, relieve jaundice and to clear away toxic material, relieve swelling in Korean Medicine. However, the effect of DH on breast cancer invasion is unknown. In this study, we investigated the inhibitory effect of DH extracts (DHE) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-9 (MMP-9) expression and cell invasion, as well as the molecular mechanisms involved in MCF-7, human breast cancer cells. DHE inhibits TPA-induced MMP-9 protein and mRNA expressions in a dose-dependent fashion. DHE also inhibited the TPA-induced transcriptional activation of nuclear factor-kappa B (NF-${\kappa}B$). These results indicate that DHE-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-${\kappa}B$ pathway in MCF-7 cells.

• Bulletin of the Korean Chemical Society
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• v.32 no.11
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• pp.3893-3898
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• 2011

Cellular uptake of double-stranded DNA (dsDNA) triggers strong innate immune responses via activation of NF-${\kappa}B$ transcription factor. However, the detailed mechanism of dsDNA-mediated innate immune response remains yet to be elucidated. Here, we show that the expression of tazarotene-induced gene 3 (TIG3) is dramatically induced by dsDNA stimulation, and the siRNA-mediated down-regulation of TIG3 mRNA results in significant suppression of dsDNA-triggered cytokine expression. Because TIG3 has been previously shown to physically interact with transglutaminase (TG) 1 to activate TG activity, and TG2 has been shown to induce NF-${\kappa}B$ activity by inducing $I{\kappa}B{\alpha}$ polymerization, we tested whether TG also plays a role in dsDNA-mediated innate immune response. Pre-treatment of TG inhibitors dramatically reduces dsDNA-triggered cytokine induction. We also show that, in HeLa cells, TG2 is the major TG, and TIG3 physically interacts with TG2. Combined together, our results suggest a novel mechanism of dsDNA-triggered innate immune response which is critically dependent on TIG3 and TG2.

• Korean Journal of Pharmacognosy
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• v.44 no.2
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• pp.104-109
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• 2013

Hesperidin (HES), a flavonone glycoside isolated from the citrus fruits such as lemons and oranges, has been reported to have many biological properties including antiinflammatory, antioxidant, and antiallergy activities. In this study, we focused on the action of HES modulating Th2-associated cytokines such as IL-4 and IL-13 expression in PMA/ionomycin (PI)-stimulated rat basophilic leukemia (RBL-2H3) cells. The production of IL-4 and IL-13 was quantified by ELISA and the mRNA expression was detected by using RT-PCR assay. In addition, western blot analysis was performed to determine the transcription factors involved in the cytokine expression. We found that HES significantly decreased PI-induced IL-4 and IL-13 productions and also decreased the level of mRNA in a dose-dependent manner. Furthermore, western blot analysis of the transcription factors implied that HES down-regulated the protein level of c-Jun and c-Fos, which are the activating protein 1 (AP-1) family and nuclear factor-kappaB (NF-${\kappa}B$) characterized as a transcription factors related to the Th2-associated cytokine expression. Taken together, our data showed that the action of HES responsible for antiallergy activities is based on suppression of Th2-associated cytokines through inhibition of AP-1 and NF-${\kappa}B$ transcription factors.

• Journal of Microbiology and Biotechnology
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• v.27 no.10
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• pp.1820-1826
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• 2017

Lipoteichoic acid (LTA), a cell wall component of gram-positive bacteria, is recognized by Toll-like receptor 2, expressed on certain mammalian cell surfaces, initiating signaling cascades that include nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$) and mitogen-activated protein kinase. There are many structural and functional varieties of LTA, which vary according to the different species of gram-positive bacteria that produce them. In this study, we examined whether LTA isolated from Staphylococcus aureus (aLTA) affects the expression of junction proteins in keratinocytes. In HaCaT cells, tight junction-related gene expression was not affected by aLTA, whereas adherens junction-related gene expression was modified. High doses of aLTA induced the phosphorylation of extracellular signal-regulated protein kinases 1 and 2, which in turn induced the epithelial-mesenchymal transition (EMT) of HaCaT cells. When cells were given a low dose of aLTA, however, NF-${\kappa}B$ was activated and the total cell population increased. Taken together, our study suggests that LTA from S. aureus infections in the skin may contribute both to the outbreak of EMT-mediated carcinogenesis and to the genesis of wound healing in a dose-dependent manner.

• International Journal of Oral Biology
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• v.36 no.1
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• pp.23-29
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• 2011

Porphyromonas gingivalis, one of the major periodontal pathogens, is implicated in the initiation and progression of periodontal disease. The initial stages of periodontal inflammation are accompanied by vascular hyperpermeability. In our present study, we report that the P. gingivalis lipopolysaccharide (LPS) increases the mRNA expression of interleukin-8 (IL-8), a major inducer of vascular permeability, in vascular endothelial cells. P. gingivalis LPS also stimulated the induction of IL-8 secretion in endothelial cells. The P. gingivalis LPS-induced expression of IL-8 was primarily modulated by nuclear factor-${\kappa}$B(NF-${\kappa}$B). P. gingivalis LPS significantly enhanced the vascular permeability both in vitro and in vivo, and a blockade of the IL-8 receptor decreased the P. gingivalis LPS-induced vascular permeability. Taken together, these results suggest that P. gingivalis LPS increases vascular permeability through the NF-${\kappa}$B-dependent production of IL-8 in vascular endothelial cells.

• Herbal Formula Science
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• v.25 no.4
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• pp.471-481
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• 2017

Objectives : Noemyeong-san (NMS) is a novel herbal prescription composed of five oriental medicinal herbs including Prunellae Spica, Betulae Cortex, Foeniculi Fructus, Asiasari Radix, and Clematidis Radix for treating Alzheimer's disease. In the present study, we investigated the effects and molecular mechanisms of NMS on BV2 microglia to evaluate the potential action of this formula for preventing or treating neurodegenerative disease such as Alzheimer's disease. Methods : To determine the cytotoxicity of NMS on BV2 microglia, the MTT assay was performed. The effects of NMS on lipopolysaccharide (LPS)-stimulated BV2 microglia were determined with a nitric oxide (NO) assay and western blots for inflammatory mediator-related proteins, mitogen activated protein kinases (MAPKs), nuclear factor kappa B (NF-${\kappa}B$) pathway-related proteins, and heme oxygenase-1 (HO-1). Result : NMS inhibited induction of iNOS and COX-2 as well as NO production without affecting the cell viability in LPS-stimulated BV2 microglia. NMS also suppressed activation of ERK and p38 MAPK among main kinases of MAPKs as well as NF-${\kappa}B$ by LPS stimulation. Furthermore, NMS dose-dependently induced the expression of HO-1 and the inhibitory effect of NMS on the production of NO were blocked by pretreatment with an HO-1 inhibitor, Snpp. Conclusions : These results demonstrate that NMS has potent anti-neuroinflammatory effect on the LPS-stimulated microglia. These findings provide evidences for NMS to be considered as a new prescription for preventing or treating neurodegenerative disease such as Alzheimer's disease.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.8
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• pp.1194-1201
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• 2015

This study investigated the effect of oxidized soybean oil in the diet of young chickens on growth performance and intestinal oxidative stress, and indices of intestinal immune function. Corn-soybean-based diets containing 2% mixtures of fresh and oxidized soybean oil provided 6 levels (0.15, 1.01, 3.14, 4.95, 7.05, and $8.97meqO_2/kg$) of peroxide value (POV) in the diets. Each dietary treatment, fed for 22 d, had 6 replicates, each containing 30 birds (n = 1,080). Increasing POV levels reduced average daily feed intake (ADFI) of the broilers during d 1 to 10, body weight and average daily gain at d 22 but did not affect overall ADFI. Concentrations of malondialdehyde (MDA) increased in plasma and jejunum as POV increased but total antioxidative capacity (T-AOC) declined in plasma and jejunum. Catalase (CAT) activity declined in plasma and jejunum as did plasma glutathione S-transferase (GST). Effects were apparent at POV exceeding $3.14meqO_2/kg$ for early ADFI and MDA in jejunum, and POV exceeding $1.01meqO_2/kg$ for CAT in plasma and jejunum, GST in plasma and T-AOC in jejunum. Relative jejunal abundance of nuclear factor kappa B ($NF-{\kappa}B$) P50 and $NF-{\kappa}B$ P65 increased as dietary POV increased. Increasing POV levels reduced the jejunal concentrations of secretory immunoglobulin A and cluster of differentiation (CD) 4 and CD8 molecules with differences from controls apparent at dietary POV of 3.14 to $4.95meqO_2/kg$. These findings indicated that growth performance, feed intake, and the local immune system of the small intestine were compromised by oxidative stress when young broilers were fed moderately oxidized soybean oil.

• Journal of Microbiology and Biotechnology
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• v.28 no.2
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• pp.190-198
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• 2018

Periodontitis is an inflammatory disease caused by microbial lipopolysaccharide (LPS), destroying gingival tissues and alveolar bone in the periodontium. In the present study, we evaluated the anti-inflammatory and anti-osteoclastic effects of panduratin A, a chalcone compound isolated from Boesenbergia pandurata, in human gingival fibroblast-1 (HGF-1) and RAW 264.7 cells. Treatment of panduratin A to LPS-stimulated HGF-1 significantly reduced the expression of interleukin-$1{\beta}$ and nuclear factor-kappa B (NF-${\kappa}B$), subsequently leading to the inhibition of matrix metalloproteinase-2 (MMP-2) and MMP-8 compared with that in the LPS control ($^{**}p$ < 0.01). These anti-inflammatory responses were mediated by suppressing the mitogen-activated protein kinase (MAPK) signaling and activator protein-1 complex formation pathways. Moreover, receptor activator of NF-${\kappa}B$ ligand (RANKL)-stimulated RAW 264.7 cells treated with panduratin A showed significant inhibition of osteoclastic transcription factors such as nuclear factor of activated T-cells c1 and c-Fos as well as osteoclastic enzymes such as tartrate-resistant acid phosphatase and cathepsin K compared with those in the RANKL control ($^{**}p$ < 0.01). Similar to HGF-1, panduratin A suppressed osteoclastogenesis by controlling MAPK signaling pathways. Taken together, these results suggest that panduratin A could be a potential candidate for development as a natural anti-periodontitis agent.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.47 no.5
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• pp.527-536
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• 2014

An ethanolic extract from Myagropsis yendoi was fractionated using several solvents. Among these, an ethyl acetate fraction (Myagropsis yendoi ethyl acetate fraction: MYE) showed the highest anti-inflammatory activity based on inhibition of lipopolysaccharides (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells. We thus investigated the molecular mechanisms underlying MYE's inhibitory effects. Pretreatment of cells with up to $30{\mu}g/mL$ of MYE significantly inhibited NO production and inducible nitric oxide synthase expression in a dose-dependent manner (P<0.05). Similarly, MYE markedly reduced the production of pro-inflammatory cytokines, such as interleukin (IL)-$1{\beta}$, IL-6, and tumor necrosis factor (TNF)-${\alpha}$, as well as their mRNA levels. While the nuclear translocation of nuclear factor-kappa B (NF-${\kappa}B$) was strongly suppressed by MYE, the activation of a nuclear factor erythroid 2-related factor (Nrf2) was increased. Moreover, MYE significantly reduced the phosphorylation of JNK, p38 MAPK, and phosphatidylinositol 3-kinase/Akt in LPS-stimulated cells. These results indicate that MYE contains anti-inflammatory compounds, and that it might be used as a dietary supplement for the prevention of inflammatory diseases.

• The Korea Journal of Herbology
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• v.27 no.4
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• pp.99-107
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• 2012

Objectives : The aim of this study was to authenticate whether fractionated extract of Rumex japonicus HOUTT. (RJ) has anti-inflammatory effects in mouse macrophage, RAW264.7 cells. Methods : Roots of RJ were extracted by methanol for 48hours. The methanol that gained was filtered and freeze dried. The methanol extract was dissolved in water and dichloromethane (DCM). After that, two layers were separated. Ethyl acetate (EA) added to the water layer and separated again. All the layers were filtered and freeze dried and the extracts were tested. Cytotoxic activity of extracts on RAW 264.7 cells was measured using MTS assay. The nitric oxide (NO) production was measured and proinflammatory cytokines and $PGE_2$ were measured by ELISA kit. The levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), I ${\kappa}$-B-${\alpha}$ and nuclear NF-${\kappa}B$ p65 expression were detected by western blot. Results : Our results indicated that DCM and EA extracts of RJ inhibited the LPS-induced NO, $PGE_2$ production and iNOS, COX-2 expression accompanied by an attenuation of TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 production in RAW 264.7 cells most effectively. DCM and EA extracts also had suppression effects of LPS-induced NF-${\kappa}B$ and MAPKs activation. Conclusions : This results demonstrate that fractionated extract of RJ has anti-inflammatory effects and among the fractioned extract, dichloromethane and ethyl acetate extract have best anti-inflammatory effects.