• The Journal of Internal Korean Medicine
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• v.25 no.2
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• pp.245-257
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• 2004

This study was done to evaluate the antiallergic effects of Naenghyohwan(NHH). Cytotoxic activity for lung fibroblast cells, cytokines transcript expression of IL-1, IL-4, IL-5, TNF-${\alpha}$, IL-6, IL-10, TGF-${\beta}$1, IFN-${\gamma}$, production of IL-4, IL-10. IFN-${\gamma}$, IgE in anti-CD40mAb plus rIL-4 stimulated murine splenic B cells and the production of histamin released in mast cells, and the expression of histamine release factor(HRF) in splenic B cells were measurd. The following results were obtained. NHH did not showed cytotoxicity in fibroblast cells. NHH increased the gene synthesis of TNF-${\alpha}$, IFN-${\gamma}$(m-RNA). NHH decreased the gene synthesis of IL-1${\beta}$, IL-4, IL-5, IL-6, TGF-${\beta}1$(m-RNA). NHH decreased the appearance of IL-4, IgE significantly. NHH increased the appearance of IL-10. IFN-${\gamma}$ significantly. NHH decreased the proliferation of B cells significantly. NHH decreased the appearance of histamin expression of HRF in mast cells significantly. The results suggest NHH is effective against the allergies. Continued studies of the antiallergic effects of NHH are urged.

• The Korean Journal of Physiology and Pharmacology
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• v.12 no.4
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• pp.165-170
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• 2008

In the present study, we aimed to identify the synergistic effects of concurrent treatment of low concentrations of cilostazol and probucol to inhibit the oxidative stress with suppression of inflammatory markers in the cultured human coronary artery endothelial cells (HCAECs). Combination of cilostazol (0.3${\sim}3{\mu}$M) with probucol (0.03${\sim}0.3{\mu}$M) significantly suppressed TNF-${\alpha}$-stimulated NAD(P)H-dependent superoxide, lipopolysaccharide (LPS)-induced intracellular reactive oxygen species (ROS) production and TNF-${\alpha}$ release in comparison with probucol or cilostazol alone. The combination of cilostazol (0.3${\sim}3{\mu}$M) with probucol (0.1${\sim}0.3{\mu}$M) inhibited the expression of vascular cell adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein-1 (MCP-1) more significantly than did the monotherapy with either probucol or cilostazol. In line with these results, combination therapy significantly suppressed monocyte adhesion to endothelial cells. Taken together, it is suggested that the synergistic effectiveness of the combination therapy with cilostazol and probucol may provide a beneficial therapeutic window in preventing atherosclerosis and protecting from cerebral ischemic injury.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.6
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• pp.397-403
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• 2011

The proliferation, migration, cytokine release, and contraction of airway smooth muscle cells are key events in the airway remodeling process that occur in lung disease such as asthma, chronic obstruction pulmonary disease, and cancer. These events can be modulated by a number of factors, including cigarette smoke extract (CSE). CSE-induced alterations in the viability, migration, and contractile abilities of normal human airway cells remain unclear. This study investigated the effect of CSE on cell viability, migration, tumor necrosis factor (TNF)-${\alpha}$ secretion, and contraction in normal human bronchial smooth muscle cells (HBSMCs). Treatment of HBSMCs with 10% CSE induced cell death, and the death was accompanied by the generation of reactive oxygen species (ROS). CSE-induced cell death was reduced by N-acetyl-l-cysteine (NAC), an ROS scavenger. In addition, CSE reduced the migration ability of HBSMCs by 75%. The combination of NAC with CSE blocked the CSE-induced reduction of cell migration. However, CSE had no effect on TNF-${\alpha}$ secretion and NF-${\kappa}B$ activation. CSE induced an increase in intracellular $Ca^{2+}$ concentration in 64% of HBSMCs. CSE reduced the contractile ability of HBSMCs, and the ability was enhanced by NAC treatment. These results demonstrate that CSE treatment induces cell death and reduces migration and contraction by increasing ROS generation in normal HBSMCs. These results suggest that CSE may induce airway change through cell death and reduction in migration and contraction of normal HBSMCs.

• Animal cells and systems
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• v.9 no.2
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• pp.101-105
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• 2005

[ ${\beta}ig-h3$ ] is a secretory protein that is induced by $TGF-{\beta}$ and implicated in various disease conditions including fibrosis. We have previously reported that ${\beta}ig-h3$ expression is implicated in astrocyte response to brain injury. In this study, we further investigated potential roles of ${\beta}ig-h3$ protein in the injured central nervous system (CNS). We specifically assessed whether the treatment of microglial cells with ${\beta}ig-h3$ can regulate microglial activity. Microglial cells are the prime effector cells in CNS immune and inflammatory responses. When activated, they produce a number of inflammatory mediators, which can promote neuronal injury. We prepared conditioned medium from the stable CHO cell line transfected with human ${\beta}ig-h3$ cDNA. We then examined the effects of the conditioned medium on the LPS- or $IFN-{\gamma}-mediated$ induction of proinflammatory molecules in microglial cells. Preincubation with the conditioned medium significantly attenuated LPS-mediated upregulation of $TNF-{\alpha},\;IL-1{\beta}$, iNOS and COX-2 mRNA expression in BV2 murine microglial cells. It also reduced $IFN-{\gamma}-mediated$ upregulation of $TNF-{\alpha}$ and COX-2 mRNA expression but not iNOS mRNA expression. Assays of nitric oxide release correlated with the mRNA data, which showed selective inhibition of LPS-mediated nitric oxide production. Although the regulatory mechanisms need to be further investigated, these results suggest that astrocyte-derived ${\beta}ig-h3$ may contribute to protection of the CNS from immune-mediated damage via controlling microglial inflammatory responses.

• Biomolecules & Therapeutics
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• v.21 no.6
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• pp.435-441
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• 2013

Emodin, a naturally occurring anthraquinone derivative isolated from Polygoni cuspidati radix, has several beneficial pharmacologic effects, which include anti-cancer, anti-diabetic, and anti-inflammatory activities. In this study, the authors examined the effect of emodin on the production of proinflammatory cytokines, such as, tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-6, in mouse bone marrow-derived mast cells (BMMCs) stimulated with phorbol 12-myristate 13-acetate (PMA) plus the calcium ionophore A23187. To investigate the mechanism responsible for the regulation of pro-inflammatory cytokine production by emodin, the authors assessed its effects on the activations of transcriptional factor nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and mitogen-activated protein kinases (MAPKs). Emodin attenuated the nuclear translocation of (NF)-${\kappa}B$ p65 and its DNA-binding activity by reducing the phosphorylation and degradation of $I{\kappa}B{\alpha}$ and the phosphorylation of $I{\kappa}B$ kinase B (IKK). Furthermore, emodin dose-dependently attenuated the phosphorylations of MAPKs, such as, extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAP kinase, and the stress-activated protein kinases (SAPK)/c-Jun-N-terminal kinase (JNK). Taken together, the findings of this study suggest that the anti-inflammatory effects of emodin on PMA plus A23187-stimulated BMMCs are mediated via the inhibition of NF-${\kappa}B$ activation and of the MAPK pathway.

• Nutrition Research and Practice
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• v.10 no.6
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• pp.623-628
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• 2016

BACKGROUND/OBJECTIVES: Obesity-induced steatohepatitis accompanied by activated hepatic macrophages/Kupffer cells facilitates the progression of hepatic fibrinogenesis and exacerbates metabolic derangements such as insulin resistance. Heme oxyganase-1 (HO-1) modulates tissue macrophage phenotypes and thus is implicated in protection against inflammatory diseases. Here, we show that the flavonoid quercetin reduces obesity-induced hepatic inflammation by inducing HO-1, which promotes hepatic macrophage polarization in favor of the M2 phenotype. MATERIALS/METHODS: Male C57BL/6 mice were fed a regular diet (RD), high-fat diet (HFD), or HFD supplemented with quercetin (HF+Que, 0.5g/kg diet) for nine weeks. Inflammatory cytokines and macrophage markers were measured by ELISA and RT-PCR, respectively. HO-1 protein was measured by Western blotting. RESULTS: Quercetin supplementation decreased levels of inflammatory cytokines ($TNF{\alpha}$, IL-6) and increased that of the anti-inflammatory cytokine (IL-10) in the livers of HFD-fed mice. This was accompanied by upregulation of M2 macrophage marker genes (Arg-1, Mrc1) and downregulation of M1 macrophage marker genes ($TNF{\alpha}$, NOS2). In co-cultures of lipid-laden hepatocytes and macrophages, treatment with quercetin induced HO-1 in the macrophages, markedly suppressed expression of M1 macrophage marker genes, and reduced release of MCP-1. Moreover, these effects of quercetin were blunted by an HO-1 inhibitor and deficiency of nuclear factor E2-related factor 2 (Nrf2) in macrophages. CONCLUSIONS: Quercetin reduces obesity-induced hepatic inflammation by promoting macrophage phenotype switching. The beneficial effect of quercetin is associated with Nrf2-mediated HO-1 induction. Quercetin may be a useful dietary factor for protecting against obesity-induced steatohepatitis.

• Archives of Plastic Surgery
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• v.37 no.1
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• pp.12-21
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• 2010

Purpose: This work aimed to elucidate the anti-inflammatory effect of pegmatite in vitro and in vivo. Methods: Author evaluated the suppressive effects of pegmatite on lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production, TNF-${\alpha}$ and IL-6 release in the RAW 264.7 murinemacrophages. Results: Treatment of RAW 264.7 cells with pegmatite significantly reduced LPS-stimulated NO production and inflammatory cytokine such as TNF-${\alpha}$ and IL-6 secretion in a concentration-dependent manner. Also pegmatite showed topical anti-inflammatory activity in the arachidonic acid (AA)-induced ear edema and acetic acid-induced increase in capillary permeability assessment in mice. It was also found that pegmatite (10 mg per ear in DW) inhibited arachidonic acid induced edema at 24 h more profoundly than 1 h by topical application. Furthermore, the vascular permeability increase induced by acetic acid was significantly reduced in mice that received pegmatite in 50 mg per mouse. Conclusion: Therefore the results of the present study suggest that pegmatite is a potent inhibitor of the LPS-induced NO and inflammatory cytokine in RAW 264.7 macrophages and showed anti-inflammatory activities in vivo animal model.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.3
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• pp.600-606
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• 2008

The purpose of this study was to investigate Anti-allergic Inflammatory Effects of Hwangyounhaedog-tang on PMA plus A23187-stimulated RBL-2H3 cells. We examined MTT assay, ${\beta}$-hexosaminidase activity, IL-4 and TNF-${\alpha}$ from RBL-2H3 after pre-treatment with HHT. In addition, we investigated expression of COX-1 and COX-2 mRNA using RT-PCR study. The results are as follows: All the concentrations of HHT from 1 to 4 mg/ml didn't have an effect on cell viability. In RBL-2H3 cells, ${\beta}$-hexosaminidase release, IL-4 and TNF-${\alpha}$ were significantly reduced by treated all concentrations of HHT. COX-2 on mRNA expression was reduced at treatment 2mg of HHT prior to stimulating by A23187. These results indicate that HHT has inhibition effects on allergy in this study.

• Journal of Microbiology and Biotechnology
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• v.27 no.2
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• pp.350-356
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• 2017

We previously reported that the CopA3 peptide (LLCIALRKK, ${\small{D}}-form$) originally isolated from the Korean dung beetle has antimicrobial and immunosuppressive effects. However, the high cost of producing the synthetic peptide, especially the ${\small{D}}-form$, has limited the development of CopA3 for therapeutic purposes. Here, we investigated whether the CopA3 deletion derivative, CopA5, which is composed of only five amino acids (LLCIA) and has the ${\small{L}}-form$ structure, could inhibit the lipopolysaccharide (LPS)-induced activation of macrophages. Peritoneal exudate macrophages (PEM) were isolated from mice and exposed to LPS in the presence or absence of CopA5, and biomarkers of macrophage activation were measured. Our results revealed that LPS-induced nitric oxide (NO) production, tumor necrosis factor $(TNF)-{\alpha}$ secretion, and phagocytic activity of PEM were significantly inhibited by CopA5 treatment. Similar to CopA3, the structurally modified CopA5 peptide had no cell toxicity (as assessed by measurement of cell viability loss and apoptosis) in PEM. Moreover, the LPS-induced upregulation of the activating phosphorylation of signal transducer and activator of transcription 1 (STAT1) was markedly inhibited by CopA5 treatment. These results suggest that, similar to CopA3, CopA5 inhibits macrophage activation by inhibiting STAT1 phosphorylation and blocking the release of NO and $TNF-{\alpha}$. CopA5 may therefore prove therapeutically useful in the realm of immune suppression.

• The Journal of Pediatrics of Korean Medicine
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• v.22 no.1
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• pp.103-111
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• 2008

Objectives Seunggal-tang is one of the prescriptions of oriental herbal medicine, which has been applied to several allergic diseases such as atopic dermatitis. This study was planned to compare differences of anti-allergic effects based on different form of Seunggal-tang by manufacturing differently. Methods Two types herb medicine products were used; aqueous extract (SG-T, Seunggal-Tang) and powder (SG-S, Seunggal-San) which were made from the same mixed formula of Seunggal-tang. To investigate in vitro anti-allergic activities, rat basophilic leukemia (RBL-2H3) cells were treated with SG-T and SG-S for 1 hour, and then stimulated with the phorbol 12-myristate 13-acetate (PMA) plus calcium ionophore A23187. We examined the release of beta-hexosaminidase, as a marker of degranulation, and the releases of tumor necrosis factor (TNF)-alpha and interleukin (IL)-4, as proinflammatory cytokines. Results SG-T and SG-S didn't have effects on cell viabilities in concentrations under 2㎎/㎖. In additionto that, SG-T more inhibited releasing ${\beta}$-hexosaminidase, TNF-${\alpha}$ and IL-4 than SG-S. Conclusions These results indicate that SG-T is more effective against mast cell-mediated allergic reactions than SG-S.