• BMB Reports
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• v.53 no.4
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• pp.223-228
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• 2020

Dysregulation of histone deacetylase 6 (HDAC6) can lead to the pathologic states and result in the development of various diseases including cancers and inflammatory diseases. The objective of this study was to elucidate the regulatory role of microRNA-22 (miR-22) in HDAC6-mediated expression of pro-inflammatory cytokines in lipopolysaccharide (LPS)-stimulated macrophages. LPS stimulation induced HDAC6 expression, but suppressed miR-22 expression in macrophages, suggesting possible correlation between HDAC6 and miR-22. Luciferase reporter assays revealed that 3'UTR of HDAC6 was a bona fide target site of miR-22. Transfection of miR-22 mimic significantly inhibited LPS-induced HDAC6 expression, while miR-22 inhibitor further increased LPS-induced HDAC6 expression. LPS-induced activation of NF-κB and AP-1 was inhibited by miR-22 mimic, but further increased by miR-22 inhibitor. LPS-induced expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 was inhibited by miR-22 mimic, but further increased by miR-22 inhibitor. Taken together, these data provide evidence that miR-22 can downregulate LPS-induced expression of pro-inflammatory cytokines via suppression of NF-κB and AP-1 axis by targeting HDAC6 in macrophages.

• The Korea Journal of Herbology
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• v.30 no.5
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• pp.23-28
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• 2015

Objectives : The aim of this study is to investigate cell viability, anti-inflammatory, antioxidant, immunoenhancing activity using various extracts of Yeonsan Ogye.Methods : In order to evaluate cytotoxicity, MTT assay was performed. We investigated production levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-αand interleukin (IL)-6, and nitric oxide(NO) in LPS-induced RAW 264.7 cells. NO production in RAW 264.7 cells was measured by using Griess reagent. Cytokines including IL-6 and TNF-αwere measured by Luminex and ROS was measured by Flow cytometry.Results : No cytotoxicity of various extracts of Yeonsan Ogye was observed in RAW 264.7 cells. Productions of ROS in RAW 264.7 cells were increased from extraction of bones and decreased from extraction of skin. Also, productions of NO in RAW 264.7 cells were increased to bone extract and decreased at skin extract. In addition, productions of pro-inflammatory cytokines (IL-6 and TNF-α) in LPS-induced RAW 264.7 cells were decreased at skin, meat extracts, respectively. Finally, the levels of immune-related cytokines (IL-6 and TNF-α) were increased compared to those of the normal group.Conclusions : It is concluded that Yeonsan Ogye extracts seem to have significant biological activities likes anti-inflammatory, antioxidant, immuno-enhancing etc. These results may be developed as a raw material for new health food and new therapeutics to ease the symptoms related with inflammatory and oxidative stress. In terms of oriental traditional medicine, we expect that it contribute to building of EBM (Evidence-Based Medicine) from the this result.

• The Journal of Pediatrics of Korean Medicine
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• v.32 no.3
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• pp.16-25
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• 2018

Objectives The purpose of this study is to investigate the anti-inflammatory effect of Lonicera Japonica-Glycyrrhiza Uralensis decoction extracts (LGE) on ulcerative colitis in children and adolescents. Methods Colitis was induced by DSS (Dextran Sulfate Sodium) in C57BL/6 mice. The sample mice were divided into group of four. The mice in the control group were not inflammation-induced. The control group was composed of untreated ulcerative colitis elicited mice. The mice in the experimental group were administered with Pentasa and another experimental group mice were treated with LGE after colitis elicitation. The effects on ulcerative colitis were evaluated by the morphological changes of colonic mucosa, decrease in the effect of pro-inflammatory cytokines ($TNF-{\alpha}$ and $NF-{\kappa}B$) and inflammatory cytokines (iNOS and COX-2) in the mucosa. Results LGE showed protective effects in DSS induced ulcerative colitis. LGE inhibited shortening of colon length and relieved the hemorrhagic erosion in colonic mucosa. LGE decreased pro-inflammatory cytokines ($TNF-{\alpha}$ and $NF-{\kappa}B$) and inflammatory cytokines (iNOS and COX-2). According to the GC/MS analysis, N-methyl pyrrolidone (NMP) was identified. Conclusions The result shows the clinical efficacy of LGE and demonstrates possible treatment options for ulcerative colitis. Further investigations for biological activity and chemical analysis of LGE will be needed.

• YAKHAK HOEJI
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• v.48 no.2
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• pp.159-164
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• 2004

Primary pro-inflammatory cytokines are a trio: tumor necrosis- $\alpha$ (TNF-$\alpha$), interleukine-$\beta$ (IL-$\beta$), and interleukine-6 (IL-6). These cytokines initiate and regulate the acute-phase inflammatory response during infection, trauma, or stress and appear to play an important role in the immune process. Nitric oxide (NO) is a multi-functional mediator, which plays an important role in regulating various biological functions in vivo. NO production by inducible nitric oxide synthase (iNOS) in macrophages is essential for the defense mechanisms against microorganisms and tumor cells. However, over-expression of iNOS by various stimuli, resulting in over-production of NO, contributes to the pathogenesis of septic shock and some inflammatory and auto-immune disease. Solvent fractions of sage ( Salvia officinalis L.), which is cultivated in Jeju-Do, was assayed for their effects on TNF-$\alpha$ and IL-6 production in LPS-stimulated RAW 264.7 macrophages. Hexane and ethylacetate (EtOAc) fraction of sage inhibited the protein and mRNA expression of TNF-$\alpha$ and IL-6 in LPS stimulated RAW 264.7 cells at the concentration of 100 $\mu\textrm{g}$/$m\ell$. Also, incubation of RAW 264.7 cells with the fraction of hexane or EtOAc (50 $\mu\textrm{g}$/$m\ell$) inhibited the LPS induced nitrite accumulation and the LPS/IFN-${\gamma}$ induced iNOS protein. And this inhibition of iNOS protein is concordant with the inhibition of iNOS mRNA expression. Above results suggest that extract of sage may have anti-inflammatory activity through the inhibition of pro-inflammatory cytokines (TNF-$\alpha$, IL-1$\beta$, IL-6), iNOS and NO.

• The Korea Journal of Herbology
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• v.31 no.5
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• pp.79-84
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• 2016

Objective : Nypa fruticans Wurmb. Fruit (NF) has been used as a conventional medicine to treat inflammatory peridontal diseases in Myanmar and Eastern Asia. However, the anti-inflammatory effect of NF aqueous extract on lipopolysaccharide (LPS)-induced inflammatory responses was not well-investigated. Therefore, this study was aimed to investigate the anti-inflammatory effect of NF on LPS-induced inflammatory responses on RAW 264.7 cells.Methods : To induce inflammation on the macrophage cell line, RAW 264.7 cells were treated with 500 ng/mL of LPS. Water extracts of NF was treated 1 h prior to treatment of LPS. Cell viability was measured by MTT assay. Production of nitrite was measured with Griess assay and pro-inflammatory cytokines such as interleukine (IL)-1β and IL-6, and tumor necrosis factor (TNF)-α was measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). In addition, we examined the inhibitory mechanisms of NF by western blot and immunocytochemistry.Result : Water Extract from NF itself did not have any cytotoxic effect at the concentration of 200 ㎍/ml in RAW 264.7 cells. Treatment of NF inhibited the production of nitrite, and pro-inflammatory cytokines inlcuding IL-1β, IL-6 and TNF-α in a dose dependant. In addition, NF treatment inhibited the LPS-induced activation and translocation of nuclear factor (NF)-κB.Conclusion : In summary, our result suggest that treatment of NF could reduce the LPS-induced inflammatory responses via deactivation of NF-κB. This study could suggest that NF could be a beneficial drug or agent to prevent inflammation.

• Food Science of Animal Resources
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• v.34 no.6
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• pp.829-835
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• 2014

Inflammatory bowel disease (IBD) is caused by dysregulation of colon mucosal immunity and mucosal epithelial barrier function. Recent studies have reported that lipoteichoic acid (LTA) from Lactobacillus plantarum K8 reduces excessive production of pro-inflammatory cytokine. In this study, we investigated the preventive effects of lysate of Lb. plantarum K8 in dextran sulfate sodium (DSS)-induced colitis. Male Sprague-Dawley rats were orally pretreated with lysate of Lb. plantarum K8 (low dose or high dose) or live Lb. plantarum K8 prior to the induction of colitis using 4% DSS. Disease progression was monitored by assessment of disease activity index (DAI). Histological changes of colonic tissues were evaluated by hematoxylin and eosin (HE) staining. Tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin-6 (IL-6) levels were measured using enzyme-linked immunosorbent assay (ELISA). The colon mRNA expressions of TNF-${\alpha}$, IL-6, and toll like receptor-2 (TLR-2) were examined by quantitative real-time-transcription polymerase chain reaction (qPCR). Lysate of Lb. plantarum K8 suppressed colon shortening, edema, mucosal damage, and the loss of DSS-induced crypts. The groups that received lysate of Lb. plantarum K8 exhibited significantly decreased levels of the pro-inflammatory cytokines TNF-${\alpha}$ and IL-6 in the colon. Interestingly, colonic expression of toll like receptor-2 mRNA in the high-dose lysate of Lb. plantarum K8 group increased significantly. Our study demonstrates the protective effects of oral lysate of Lb. plantarum K8 administration on DSS-induced colitis via the modulation of pro-inflammatory mediators of the mucosal immune system.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.3
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• pp.728-735
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• 2007

This study was carried out to know the effect of Gwanjulbang-5(hereinafter refer to GJB-5) to on Rheumatoid Arthritis by using human fibroblast-like synoviocytes(hFLS). We performed several experimetal items : that is cytotoxicity of GJB-5, mRNA expression of pro-imflammatory cytokines in hFLS and production of NO, ROS. The results were obtained as follows : GJB-5 reduced the production of pro-inflammatory cytokines TNF-${\alpha}$, IL-1${\beta}$, IL-6, IL-8 in hFLS, increased the production of TIMP-1. As well as GJB-5 reduced the production of ICAM-1, MMP-3, NOS-II, the production of NO and ROS, and the proliferation of hFLS in proportion to the concentration of GJB-5. In conclusion, these results shows that GJB-5 had immunomodulatory effects in treating rheumatoid arthritis.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.92-92
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• 2018

Solanum nigrum L. (SNL), generally known as black nightshade, is traditionally used as medicine to reduce inflammation caused by several diseases like asthma, chronic bronchitis and liver cirrhosis. In this study, anti-inflammatory effects of SNL extract were examined and possible molecular mechanisms of the anti-inflammatory effects were investigated. The inhibitory effects of SNL extract on nitric oxide (NO), pro-inflammatory cytokines ($TNF-{\alpha}$, IL-6) and Matrix metallopeptidase 9 (MMP-9) productions were dissected using lipopolysaccharide (LPS) stimulated murine macrophage-like cell line Raw264.7 cells and human microglial cell line BV2 cells. We further investigated whether SNL extract could suppress the phosphorylation of ERK1/2, JNK, and p38 and the nuclear expression of nuclear factor $NF-{\kappa}B$ p65 in LPS-stimulated Raw264.7 cells and BV2 cells. As a result, we showed that the SNL extract significantly decreased the production of pro-inflammatory cytokines, NO, and MMP-9. In addition, the SNL strongly inhibited the phosphorylation of ERK1/2, JNK, p38 and nuclear translocation of $NF-{\kappa}B$ p65 in activated cells. We confirmed that the extracts of SNL effectively inhibits the anti-inflammatory and may be used as a therapeutic to various inflammatory diseases.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2019.04a
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• pp.115-115
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• 2019

Arctium minus (AM), commonly known as lesser burdock, is a dried fruit (seed) of Aructium lappa L. that belong to Asteraceae. It has been used traditionally as herbal medicine because of its anti-inflammatory effects, and it has been applied to treat various diseases like allergies, skin aging, hyperlipidemia and urinary stone. In this study, we investigated the inhibitory effects of AM on the production of pro-inflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Pre-treatment of the RAW 264.7 cells with AM considerably inhibited and reduced production of Nitric Oxide (NO) and pro-inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and also shows suppression of nuclear factor-kappa B (NF-${\kappa}B$) translocation. In addition, AM treatment considerably reduced phosphorylation of mitogen-activated protein kinase (MAPK) in LPS-stimulated RAW 264.7 cells. Our results indicate that the AM has potential to inhibit inflammation through suppressing production of inflammatory mediators via both the NF-${\kappa}B$ and MAPK signaling pathway. We therefore suggest that AM might be effective therapeutics for the treatment of various inflammatory diseases.

• 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.