• The Korea Journal of Herbology
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• v.36 no.1
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• pp.67-76
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• 2021

Objective : Yukgunja-tang is one of the herbal prescriptions widely used for functional indigestion. In this study, we evaluated the pharmacological effect through the Yukgunja-tang formulation development. Methods : The RAW 264.7 cells were pretreated with Yukgunja-tang tablet (YGJT-T : 50, 100 and 200 ㎍/㎖) and then stimulated with lipopolysaccharide (LPS : 500 ng/㎖). Cell viability, inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2) and inflammatory cytokines (IL-1β, IL-6, and TNF-α) were measured. Also, ICR mice induced acute gastritis by oral administration of 150 mM HCl in 60% ethanol. The YGJT-T (30 mg/kg) was pretreated for 3 days, and 150 mM HCl in 60% ethanol was orally administered 1 hour after the last drug treatment. Mice were sacrificed 1 hour after oral administration of 150 mM HCl in 60% ethanol. The gastric mucosa was observed, and inflammatory cytokines in the gastric tissue were measured. Results : The marker components of YGJT-T were determined by simultaneous analysis using HPLC. In RAW 264.7 cells, pretreatment of YGJT-T was non-toxic and inhibited the production of inflammatory mediators such as NO and PGE2 and suppressed inflammatory cytokines. In addition, pretreatment of YGJT-T improved bleeding and edema due to gastric lesions caused by acute gastritis and suppressed inflammatory cytokines. Conclusion : In summary, our results confirmed that treatment with YGJT-T has anti-inflammatory and anti-gastritis effects in vitro and in vivo. Therefore, in this study, YGJT-T could support a potential strategy for the prevention and treatment of gastritis.

• The Journal of Korean Obstetrics and Gynecology
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• v.34 no.4
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• pp.12-29
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• 2021

Objective: This study was performed to investigate the inhibitory effect of Cheongpochukeo-tang (CCT) on lipopolysaccharide (LPS)-induced inflammation model. Methods: RAW 264.7 cells were pre-treated with CCT and incubated with LPS (500 ng/ml) after 1 hour. Cell viability was measured by MTT assay to figure out cytotoxicity of CCT. The production of nitric oxide and mRNA expression of pro-inflammatory cytokine were measured. And the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) were examined to figure out molecular mechanisms of CCT's anti-inflammatory effects. In addition, mice survival rate and cytokine levels of serum were observed after treated with CCT. And mice liver tissues were observed and their cytokines levels in liver tissue were measured. Results: CCT did not have cytotoxic effect in RAW 264.7 cells. It inhibited LPS-induced nitric oxide (NO) production, but showed an increase in NO by itself at 2 mg/ml concentration. CCT inhibited mRNA expression of IL-1β, IL-6, TNF-α in a dose dependant and the activaton of MAPKs and NF-κB. In addition, CCT reduced mortality in the LPS-induced mouse model and inhibited production of cytokines in mouse serum and liver tissue. Conclusion: The results suggest that CCT could reduce LPS-induced inflammation by inhibiting MAPKs and NF-κB activaton, NO production, and pro-inflammatory cytokines secretion. Thereby, CCT could be effective medicine for the inflammatory disease.

• The Journal of Internal Korean Medicine
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• v.30 no.3
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• pp.612-623
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• 2009

Objectives : The water extract of Sopung-tang (SPT) has been traditionally used in the treatment of acute stroke in Oriental Medicine. Pro-inflammatory cytokines play a critical role in the onset of post-ischemic inflammatory cascades. The present study was designed to investigate the effects of SPT on pro-inflammatory cytokine production in a photothrombotic ischemia mouse model. Methods : After SPT oral administration to the mice for five days, with using Rose Bengal and cold light, photothrombotic ischemia lesion was induced in stereotactically held male BALB/c mice. Also, results including, gross finding lesion size, histopathological finding changes, and inflammatory cytokine expression changes from the photothrombotic ischemia mouse model were observed. Results : The photothrombotic ischemia lesion was decreased by the oral injection of SPT. Also, SPT inhibited the expression of TNF-$\alpha$, IL-$1{\beta}$, IL-6, the active form of caspase-3 protease, and transglutaminase-2 in the photothrombotic ischemia lesion. Conclusions : These results suggest that SPT protects the ischemic death of brain cells through suppression of the production of anti-inflammatory cytokines and catalytic activation of caspase-3 protease in the photothrombotic ischemia mouse model.

• The Korea Journal of Herbology
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• v.25 no.4
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• pp.103-112
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• 2010

Objective : The aim of this study was to determine whether methanol extract of Do-Ki-Tang (DKT) inhibit free radical generation and production of nitrite an index of NO, $PGE_2$, iNOS, COX-2 and pro-inflammatory cytokines such as TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Methods : Cytotoxic activity of extract on RAW 264.7 cells was measured using 5-(3-caroboxymeth-oxyphenyl)-2H-tetra-zolium inner salt (MTS) assay. The expression level of inflammatory response-related proteins was confirmed by western blot. The production of proinflammatory cytokines was measured by ELISA. Results : Our results indicated that DKT scavenged DPPH radical and nitric oxide in vitro. Moreover, DKT significantly inhibited the LPS-induced NO, $PGE_2$ production and iNOS, COX-2 expression accompanied by an attenuation of TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 formation in macrophages. Furthermore, DKT treatment also blocked LPS-induced intracellular ROS production and the activation of NF-${\kappa}B$ and MAPKs. Conclusion : Our data suggest that the anti-inflammatory effect of DKT is mediated through down-modulation of pro-inflammatory mediators and cytokines by blocking the signaling pathways of NF-${\kappa}B$ and MAPKs. These inhibitory effects by DKT represent a potential therapeutic approach to the treatment of inflammatory diseases.

• Journal of Microbiology and Biotechnology
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• v.25 no.2
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• pp.296-301
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• 2015

Chronic kidney diseases are based on uncontrolled immunological and inflammatory responses to pathophysiological renal circumstances such as glomerulonephritis, which is caused by immunological mechanisms of glomerular inflammation with increased production of renal pro-inflammatory cytokines. Pentoxifylline (PTX) exhibits anti-inflammatory properties by inhibiting cytokine and chemokine production through aggregation of erythrocytes and thrombocytes. We synthesized a series of 1,7-substituted methylxanthine derivatives by the Traube purine reaction, and the formation of purine ring was completed through nitrosation, a reduction of the nitroso to the amine by catalytic hydrogenation as derivatives of PTX. Then we studied biological activities such as renal anti-inflammatory effects of the synthesized compounds in the production of cytokines such as nitric oxide (NO), interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) and of chemokines such as monocyte chemoattractant protein-1 and IL-8 in Raw 264.7 and HK-2 cells. Renal antiinflammatory activities of this novel series of N-1 and N-7-substituted methylxanthine showed that the N-7 methyl-group-substituted analogs (S7b) showed selective 61% and 77% inhibition of the production of NO and IL-8. The other replacement of the N-1-(CH₂)₄COCH₃ roup, as in the case of compound S6c, also showed an effective 50% and 77% inhibition of TNF-α and IL-8 production in LPS-stimulated Raw 264.7 and HK-2 cells.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.1
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• pp.26-34
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• 2012

This study is to investigate the effects of Chinemys reevesii (CR) on allergic inflammation mechanism related chronic dermatitis. To investigate the effects of CR, we study inhibitory effect of CR on the levels of pro-inflammatory cytokines released from RAW 264.7 cell stimulated with lipopolysaccaride (LPS), and EoL-1, THP-1, Jutkat cell stimulated with Dermatophagoides pteronyssinus (DP), and LPS induced acute inflammatory BALB/c mouse model. CR reduced the levels of IL-$1{\beta}$ released from RAW 264.7 cell stimulated with LPS at 20 ug/ml, 10 ug/ml concentration. CR significantly reduced the levels of MCP-1 released from EoL-1 cell, IL-6 from THP-1 cell, and IL-4, IL-5, TNF-${\alpha}$ from Jutkat cell stimulated with DP at all the concentration. CR significantly reduced the levels of TNF-${\alpha}$, IL-6, IL-$1{\beta}$, in LPS induced inflammatory BALB/c mouse model, in a dose-dependent manner. These results suggested that CR has suppressive effects on pro-inflammatory cytokines in various inflammation related cell lines through the regulation of immune system. CR could be a therapeutic agent for treatment of chronic inflammatory dermatitis in the future.

• Nutrition Research and Practice
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• v.10 no.1
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• pp.42-48
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• 2016

BACKGROUND/OBJECTIVES: Seaweeds have been reported to have various health beneficial effects. In this study, we investigated the potential anti-obesity and anti-inflammatory effects of four types of domestic brown seaweeds in a high-fat diet-induced obese mouse model and bone marrow-derived macrophages (BMDM). MATERIALS/METHODS: Male C57BL/6N mice were fed low-fat diet (LFD), high-fat diet (HFD) or HFD containing Undaria Pinnatifida, HFD containing Laminaria Japonica (LJ), HFD containing Sargassum Fulvellum, or HFD containing Hizikia Fusiforme (HF) for 16 weeks. RESULTS: Brown seaweed supplementation did not affect long-term HFD-associated changes in body weight or adiposity, although mice fed HFD + LJ or HFD + HF gained slightly less body weight compared with those fed HFD at the beginning of feeding. Despite being obese, mice fed HFD + LJ appeared to show improved insulin sensitivity compared to mice fed HFD. Consistently, we observed significantly reduced blood glucose concentrations in mice fed HFD + LJ compared with those of mice fed HFD. Although no significant differences in adipocyte size were detected among the HFD-fed groups, consumption of seaweeds decreased formation of HFD-induced crown-like structures in gonadal adipose tissue as well as plasma inflammatory cytokines. BMDM from mice fed HFDs with seaweeds showed differential regulation of pro-inflammatory cytokines such as IL-$1{\beta}$ and IL-6 compared with BMDM from mice fed HFD by LPS stimulation. CONCLUSION: Although seaweed consumption did not prevent long-term HFD-induced obesity in C57BL/6N mice, it reduced insulin resistance (IR) and circulation of pro-inflammatory cytokines. Therefore, seaweeds may ameliorate systemic inflammation and IR in obesity partially due to inhibition of inflammatory signaling in adipose tissue cells as well as bone marrow-derived immune cells.

• The Journal of Korean Medicine
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• v.39 no.4
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• pp.40-50
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• 2018

Objectives: The aim of this study is to investigate anti-inflammatory effects of Kyungheechunggan-tang (KHCGT) on LPS- induced RAW 264.7 cells and LX-2 cells and anti-fibrotic effects of KHCGT on LX-2 cells. Materials and Methods: Three types of KHCGTs (KHCGT-A, -B, and -C) by narrowing down the number of constituent herbs from 9 (KHCGT-A) to 5 (KHCGT-B) and to 3 (KHCGT-C) were developed. To understand pharmacological effects of KHCGT, three types of KHCGTs were treated on RAW 264.7 cells and LX-2 cells. Anti-inflammatory activities of KHCGT were evaluated by ELISA assay for pro-inflammatory cytokines, IL-6, $TNF-{\alpha}$ and IL-10, in LPS-stimulated RAW 264.7 cells and for IL-6 production in LPS-induced LX-2 cells. In addition, anti-fibrotic effects of KHCGT were determined by quantitative real-time PCR assay for fibrosis-related genes, ${\alpha}-SMA$, collagen1A1, TIMP1, MMP-2, in LX-2 cells. Results: KHCGT-A and KHCGT-C showed inhibitory effects on secretion of IL-6 in LPS-stimulated RAW 264.7 cells and LX-2 cells. KHCGT-B and KHCGT-C exhibited inhibitory effects on the expression of pro-inflammatory cytokines such as IL-6, $TNF-{\alpha}$, and IL-10 in LPS-stimulated RAW 264.7 cells. The mRNA expression levels of collagen1A1 and MMP-2 were significantly reduced by KHCGT-C whereas TIMP-1 was suppressed by KHCGT-A and KHCGT-B in LX-2 cells. Among three different formulas, KHCGT-C demonstrated the most remarkable effects on inflammation and fibrosis. Conclusions: In this study, KHCGT showed both anti-inflammatory and anti-fibrotic effects which make it to be a prospective agent for chronic liver diseases with inflammation and fibrosis.

• Preventive Nutrition and Food Science
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• v.17 no.2
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• pp.109-115
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• 2012

This study was designed to investigate the inhibitory effects of Perilla frutescens (L.) Britton var. frutescens extract on the production of inflammation-related mediators (NO, ROS, NF-${\kappa}B$, iNOS and COX-2) and pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages. Perilla frutescents (L.) Britton var. frutescens was air-dried and extracted with ethanol. The extract dose-dependently decreased the generation of intracellular reactive oxygen species and dose-dependently increased antioxidant enzyme activities, such as superoxide dismutase, catalase and glutathione peroxidase in lipopolysaccharide stimulated RAW 264.7 macrophages. Also, Perilla frutescens (L.) Britton var. frutescens extract suppressed NO production in lipopolysaccharide-stimulated RAW 264.7 cells. The expressions of pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$ and IL-6), NF-${\kappa}B$, iNOS and COX-2 were inhibited by the treatment with the extract. Thus, this study shows the Perilla frutescens (L.) Britton var. frutescens extract could be useful for inhibition of the inflammatory process.

• Journal of Microbiology and Biotechnology
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• v.30 no.12
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• pp.1810-1818
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• 2020

Inhibitor K562 (IK) protein was first isolated from the culture medium of K562 cells, a leukemia cell line, and is an inhibitory regulator of interferon-γ-induced major histocompatibility complex class II expression. Recently, exogenous truncated IK (tIK) protein showed potential as a therapeutic agent for inflammation-related diseases. In this study, we designed a novel putative anti-inflammatory peptide derived from tIK protein based on homology modeling of the human interleukin-10 (hIL-10) structure, and investigated whether the peptide exerted inhibitory effects against pro-inflammatory cytokines such as IL-17 and tumor necrosis factor-α (TNF-α). The peptide contains key residues involved in binding hIL-10 to the IL-10 receptor, and exerted strong inhibitory effects on IL-17 (43.8%) and TNF-α (50.7%). In addition, we used circular dichroism spectroscopy to confirm that the peptide is usually present in a random coil configuration in aqueous solution. In terms of toxicity, the peptide was found to be biologically safe. The mechanisms by which the short peptide derived from human tIK protein exerts inhibitory effects against IL-17 and TNF-α should be explored further. We also evaluated the feasibility of using this novel peptide in skincare products.