• Title/Summary/Keyword: I$\kappa$B$\alpha$

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Nelumbinis Folium Methanol Extract Regulates Inducible Nitric Oxide Synthase Signaling Pathways in Mouse Peritoneal Macrophages (하엽(荷葉) 메탄올 추출물의 마우스 대식세포 inducible nitric oxide synthase 합성과 신호전달에 대한 조절)

  • Lee, Si-Eun;Lee, Mi-Hwa;Choi, Ho-Young;Sohn, Nak-Won;Kang, Hee
    • The Korea Journal of Herbology
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    • v.27 no.1
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    • pp.65-71
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    • 2012
  • Objective : Nelumbinis Folium (NF) is used for diarrhea, headache and dizziness in traditional medicine. In this paper, we examined the anti-inflammatory effects of the methanol extract of NF in mouse macrophages. Methods : Peritoneal macrophages from thioglycollate medium-injected mice were cultured and stimulated with lipopolysaccharide(LPS) or LPS/interferon(IFN)-${\gamma}$ for viability assay, cytokine measurement and Western blotting. Results : NF methanol extract suppressed the levels of nitric oxide (NO) through reduction of inducible NO synthase in a concentration-dependent manner. The extract reduced LPS/IFN-${\gamma}$-stimulated STAT1 phosphorylation and LPS-induced $I{\kappa}B{\alpha}$ degradation through inhibition of $I{\kappa}B{\alpha}$ kinase activation. The extract also inhibited p38, JNK/SAPK and ERK1/2 activation. Conclusions : Our findings suggested that NF has anti-inflammatory activity, and have a potential for therapeutic application. Further research is required to investigate its anti-inflammatory active compounds.

The Anti-Inflammatory Effect of Lonicera Japonica-Glycyrrhiza Uralensis Decoction on Ulcerative Colitis Induced by DSS in Mice (항염증조절을 통한 금은화-감초 복합 추출물의 DSS 유도 궤양성 대장염 완화 효과)

  • Lee, Yeon Woo;Ahn, Sang Hyun;Kim, Ho Hyun;Kim, Kibong
    • 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.

Anti-oxidative and anti-inflammatory effect of Do-Ki-Tang methanol extract in mouse macrophage cells (마우스 대식세포에서 도기탕 (導氣湯) 메탄올 추출물의 항산화 및 항염증 효과)

  • Kim, Dong-Wan;Yun, Hyun-Jeong;Heo, Jun-Young;Kim, Tae-Hoon;Cho, Hyun-Jin;Park, Sun-Dong
    • 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.

The anti-oxidant and anti-inflammatory Activites of Changchulgeumryeontang Extract (창출금련탕(蒼朮芩連湯) 추출물의 항산화 및 항염증 활성에 미치는 영향)

  • Won, Hea-Ryeon;Park, Hye-Su;Kim, Ee-Hwa;Kim, Yong-Min
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.31 no.4
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    • pp.1-12
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    • 2018
  • Objectives : This study investigated the anti-oxidant and anti-inflammatory activities of Changchulgeumryeontang (CCGRT) extract. Methods : The macrophage cell line RAW 264.7 cells were used and MTT assay was performed to measure the cell viabilities at the various concentrations of CCGRT ($25-200{\mu}g/m{\ell}$). Nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) were measured in LPS-induced RAW 264.7 cells. Expressions of iNOS, $NF-{\kappa}B$, $IL-1{\alpha}$, $IL-1{\beta}$ and IL-6 were also performed by real-time PCR. The anti-oxidant activities of CCGRT was measured by DPPH radical scavenging activity. Results : 1. there was no cytotoxicity in RAW264.7 cells treated with CCGRT compared to the control. 2. CCGRT treated group significantly inhibited NO and $PGE_2$ production compared to the LPS treated group. 3. CCGRT treated group significantly decreased mRNA expressions of iNOS, $NF-{\kappa}B$, $IL-1{\alpha}$, $IL-1{\beta}$ and IL-6 compared to the LPS treated group. 4. CCGTR was found to have high DPPH free radical scavenging ability. Conclusions : According to the above results, CCGRT may be a potentional choice for the treatment of inflammatory skin disease. Conclusions : According to the above results, CCGRT may be a potentional choice for the treatment of inflammatory skin disease.

Ginsenoside Rc from Panax ginseng exerts anti-inflammatory activity by targeting TANK-binding kinase 1/interferon regulatory factor-3 and p38/ATF-2

  • Yu, Tao;Yang, Yanyan;Kwak, Yi-Seong;Song, Gwan Gyu;Kim, Mi-Yeon;Rhee, Man Hee;Cho, Jae Youl
    • Journal of Ginseng Research
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    • v.41 no.2
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    • pp.127-133
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    • 2017
  • Background: Ginsenoside Rc (G-Rc) is one of the major protopanaxadiol-type saponins isolated from Panax ginseng, a well-known medicinal herb with many beneficial properties including anticancer, anti-inflammatory, antiobesity, and antidiabetic effects. In this study, we investigated the effects of G-Rc on inflammatory responses in vitro and examined the mechanisms of these effects. Methods: The in vitro inflammation system used lipopolysaccharide-treated macrophages, tumor necrosis $factor-{\alpha}/interferon-{\gamma}-treated$ synovial cells, and HEK293 cells transfected with various inducers of inflammation. Results: G-Rc significantly inhibited the expression of macrophage-derived cytokines, such as tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$. G-Rc also markedly suppressed the activation of TANK-binding kinase $1/I{\kappa}B$ kinase ${\varepsilon}/interferon$ regulatory factor-3 and p38/ATF-2 signaling in activated RAW264.7 macrophages, human synovial cells, and HEK293 cells. Conclusion: G-Rc exerts its anti-inflammatory actions by suppressing TANK-binding kinase $1/I{\kappa}B$ kinase ${\varepsilon}/interferon$ regulatory factor-3 and p38/ATF-2 signaling.

Protective Effect of Polygonum Multiflorum on Cell Damage in UVB-irradiated HaCaT Keratinocytes (적하수오(赤何首烏)의 UVB로 자극한 피부 각질세포 보호 작용)

  • Lee, Seung-Ah;Yoo, Dong-Youl
    • The Journal of Korean Obstetrics and Gynecology
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    • v.24 no.4
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    • pp.31-49
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    • 2011
  • Objectives: This study was performed to assess the protective effect of Polygonum multiflorum(PM) on UVB-irradiated HaCaT Keratinocytes damage. Methods: The protective effects of Polygonum multiflorum(PM) were determined by UVB-irradiated HaCaT assay. We assessed protective effects of Polygonum multiflorum(PM) on LDH release and nitrite production from HaCaT. COX-2, Bcl-2, Bax, $TNF{\alpha}$, c-jun, c-fos, NF-${\kappa}B$, iNOS, Bcl-xL gene expression were determined in HaCaT using real-time PCR method. Results: 1. PM inhibited LDH Release in UVB-irradiated HaCaT Keratinocytes. 2. PM inhibited Nitrite Production in UVB-irradiated HaCaT Keratinocytes. 3. PM suppressed the Gene Expression of COX-2 in UVB-irradiated HaCaT Keratinocytes. 4. PM increased the Gene Expression of Bcl-2 in UVB-irradiated HaCaT Keratinocytes. 5. PM didn't increase the Gene Expression of Bax in UVB-irradiated HaCaT Keratinocytes. 6. PM suppressed the Gene Expression of $TNF{\alpha}$ in UVB-irradiated HaCaT Keratinocytes. 7. PM suppressed the Gene Expression of c-jun in UVB-irradiated HaCaT Keratinocytes. 8. PM suppressed the Gene Expression of c-fos in UVB-irradiated HaCaT Keratinocytes. 9. PM suppressed the Gene Expression of NF-${\kappa}B$ in UVB-irradiated HaCaT Keratinocytes. 10. PM suppressed the Gene Expression of i-NOS in UVB-irradiated HaCaT Keratinocytes. 11. PM didn't increase the Gene Expression of Bcl-xL in UVB-irradiated HaCaT Keratinocytes Conclusions: In conclusion, these results suggest that PM inhibited the cell damage in UVB-irradiated HaCaT.

Immunomodulatory Effects of Dioscoreae Rhizome Against Inflammation through Suppressed Production of Cytokines Via Inhibition of the NF-${\kappa}B$ Pathway

  • Kim, Seulah;Shin, Seulmee;Hyun, Bobae;Kong, Hyunseok;Han, Shinha;Lee, Aeri;Lee, Seungjeong;Kim, Kyungjae
    • IMMUNE NETWORK
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    • v.12 no.5
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    • pp.181-188
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    • 2012
  • Dioscoreae Rhizome (DR) has been used in traditional medicine to treat numerous diseases and is reported to have anti-diabetes and anti-tumor activities. To identify a bioactive traditional medicine with anti-inflammatory activity of a water extract of DR (EDR), we determined the mRNA and protein levels of proinflammatory cytokines in macrophages through RT-PCR and western blot analysis and performed a FACS analysis for measuring surface molecules. EDR dose-dependently decreased the production of NO and pro-inflammatory cytokines such as IL-$1{\beta}$, IL-6, TNF-${\alpha}$, and $PGE_2$, as well as mRNA levels of iNOS, COX-2, and pro-inflammatory cytokines, as determined by western blot and RT-PCR analysis, respectively. The expression of co-stimulatory molecules such as B7-1 and B7-2 was also reduced by EDR. Furthermore, activation of the nuclear transcription factor, NF-${\kappa}B$, but not that of IL-4 and IL-10, in macrophages was inhibited by EDR. These results show that EDR decreased pro-inflammatory cytokines via inhibition of NF-${\kappa}B$-dependent inflammatory protein level, suggesting that EDR could be a useful immunomodulatory agent for treating immunological diseases.

Immunostimulatory Effects of Cordyceps militaris on Macrophages through the Enhanced Production of Cytokines via the Activation of NF-${\kappa}B$

  • Shin, Seul-Mee;Kwon, Jeong-Hak;Lee, Sung-Won;Kong, Hyun-Seok;Lee, Seung-Jeong;Lee, Chong-Kil;Cho, Kyung-Hae;Ha, Nam-Joo;Kim, Kyung-Jae
    • IMMUNE NETWORK
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    • v.10 no.2
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    • pp.55-63
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    • 2010
  • Background: Cordyceps militaris has been used in traditional medicine to treat numerous diseases and has been reported to possess both antitumor and immunomodulatory activities in vitro and in vivo. However, the pharmacological and biochemical mechanisms of Cordyceps militaris extract (CME) on macrophages have not been clearly elucidated. In the present study, we examined how CME induces the production of proinflammatory cytokines, transcription factor, and the expression of co-stimulatory molecules. Methods: We confirmed the mRNA and protein levels of proinflammatory cytokines through RT-PCR and western blot analysis, followed by a FACS analysis for surface molecules. Results: CME dose dependently increased the production of NO and proinflammatory cytokines such as IL-$1{\beta}$, IL-6, TNF-${\alpha}$, and $PGE_2$, and it induced the protein levels of iNOS, COX-2, and proinflammatory cytokines in a concentrationdependent manner, as determined by western blot and RT-PCR analysis, respectively. The expression of co-stimulatory molecules such as ICAM-1, B7-1, and B7-2 was also enhanced by CME. Furthermore, the activation of the nuclear transcription factor, NF-${\kappa}B$ in macrophages was stimulated by CME. Conclusion: Based on these observations, CME increased proinflammatory cytokines through the activation of NF-${\kappa}B$, further suggesting that CME may prove useful as an immune-enhancing agent in the treatment of immunological disease.

Effects of GuBoEum Inhibiting NO, TNF-$\alpha$, IL-6 and IL-12 Production by Blocking MAP Kinase Activation in LPS-induced Murine Macrophages (LPS로 유도한 대식세포에서 MAP kinase의 억제에 의한 구보음(九寶飮)의 NO, TNF-$\alpha$, IL-6, IL-12 생성 억제 효과)

  • Lee, Byung-Soon;Shin, Jo-Young;Lee, Si-Hyeong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.1
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    • pp.104-112
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    • 2009
  • The purpose of this study was to investigate the anti-inflammatory effects of extract from GuBoEum(GBE) on the peritoneal macrophage. To evaluate anti-inflammatory effects of GBE. I measured cytokines (interleukin-6; IL-6, interleukin-12; IL-12, tumor necrosis factor-$\alpha$; TNF-$\alpha$) and nitric oxide (NO) production in lipopolysacchride (LPS)-induced macrophages. Furthermore, I examined molecular mechanism using western blot and also LPS-induced endotoxin shock. Extract from GBE does not have any cytotoxic effect in the peritoneal macrophages. Extract from GBE reduced LPS-induced IL-6, TNF-$\alpha$, IL-12 and NO production in peritoneal macrophages. GBE inhibited the activation of extracelluar signal-regulated kinase (ERK), C-Jun $NH_2$-terminal kinase (JNK) but not of p38, degradation of $I{\kappa}B-{\alpha}$ in the LPS-stimulated peritoneal macrophages. GBE inhibited the production of TNF-$\alpha$, IL-6 and IL-12 in serum after LPS injection. These results suggest that GBE may inhibit the production of TNF-$\alpha$, IL-6, and IL-12 through inhibition of ERK and JNK activation, and that GBE may be beneficial oriental medicine for inflammatory diseases.

Anti-Inflammatory Effect of Licochalcone E, a Constituent of Licorice, on Lipopolysaccharide-Induced Inflammatory Responses in Murine Macrophages (Licochalcone E의 항염증 효과와 그 기전에 대한 연구)

  • Park, Geun-Mook;Jun, Jong-Gab;Kim, Jin-Kyung
    • Journal of Life Science
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    • v.21 no.5
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    • pp.656-663
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    • 2011
  • Licochalcone, a major phenolic constituent of the licorice species Glycyrrhiza inflata, a constituent of licorice, exhibits various biological properties, including chemopreventive-, antibacterial-, and anti-spasmodic activities. Recently, Licochalcone E (LicE) was isolated from the roots of Glycyrrhiza inflate, however its biological functions have not been fully examined. In the present study, we investigated the ability of LicE to regulate inflammation reactions in macrophages. Our in vitro experiments using murine macrophages, RAW264.7 cells, showed that LicE suppressed not only nitric oxide (NO) and prostaglandin $E_2$ generation, but also the expression of inducible NO synthase and cyclooxygenase-2 induced by lipopolysaccharide (LPS). Similarly, LicE inhibited the release of proinflammatory cytokines induced by LPS in RAW264.7 cells, including tumor necrosis factor-${\alpha}$ and interleukin-6. The underlying mechanism of LicE on anti-inflammatory action correlated with down-regulation of the nuclear factor-${\kappa}$B. Our data collectively indicate that LicE inhibited the production of several inflammatory mediators and might be used in the treatment of various inflammatory diseases.