• Journal of Sasang Constitutional Medicine
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• v.21 no.1
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• pp.139-149
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• 2009

1. Objectives The roots of Sophora flavescens Aiton (SFA) are widely used as a herbal remedy for allergic inflammation. In this study, we invested the effect of SFA on passive cutaneous anaphylaxis reaction and histamin releas and we demonstrated that SFA suppressed the production of pro-inflammatory cytokines, such as tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin- 6 (IL-6), and interleukin -8 (IL-8), through inhibition of the $NF{\kappa}B$, JNK and p38 pathway in the human mast cell line, HMC-1. 2. Methods To accomplish this, we invested passive cutaneous anaphylaxis reaction and histamin release at an animal experiment. In addition, we investigated the effect of SFA on the production of inflammation-related cytokines in HMC-1 cells that were co-treated with PMA and A23187, which can induce production of pro-inflammatory cytokines. 3. Results and Conclusions SFA induced passive cutaneous anaphylaxis reaction and histamin releas and supressed the expression of TNF-${\alpha}$, IL-6, and IL-8. In addition, the protein levels of TNF-${\alpha}$ were also decreased by SFA treatment. Furthermore, SFA inhibited the nuclear translocation of nuclear factor $NF{\kappa}B$ through inhibition of the phosphorylation and degradation of $I{\kappa}B-{\alpha}$, which is an inhibitor of $NF{\kappa}B$. Moreover, SFA also inhibited induction of MAPKs (JNK, p38) and $NF{\kappa}B$ promoter-mediated luciferase activity. Taken together, these results suggest that SFA could be used as a treatment for mast cell-derived allergic inflammatory diseases.

• Journal of Acupuncture Research
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• v.22 no.5
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• pp.37-48
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• 2005

Objectives : The purpose of this study was to investigate the anti-caner effect of cobrotoxin on the prostatic cancer cell line(PC-3). Methods : After the treatment of PC-3 cells with cobrotoxin, we performed fluorescence microscope, MTT assay, Western blotting, Flow cytometry, PAGE electrophoresis and Surface plasmon resonance analysis to identify $NF-{\kappa}B$ the change of calcium and NO. Results : 1. The expression of $NF-{\kappa}B$ was decreased at 1nM and It·as decreased significantly at 2, 4, 8nM. 2. $I{\kappa}B,\;NF-{\kappa}B$ inhibitor, was decreased significantly at 8nM and $p-l{\kappa}Ba$, phosphrylation of $I{\kappa}B$, was decreased significantly at all concentrations of cobrotoxin. 3. The expressions of p50 and p65 were decreased significantly and dose-dependently at 1, 2, 4, 8nM. 4. The expression of p53 was increased significantly at 1, 2, 4, 8nM. 5. The calcium concentration in cell wasn't changed at 1, 2, 4, 8nM, but was increased dose-dependently at 30, 70, 130, 250nM comparing with lower dose of cobrotoxin. 6. The NO concentration in cell was increased significantly at 1, 2, 4, 8nM. 7. In immunochemical staining, we found that cobrotoxin-immunochemical complex move into intracellular space dose-dependently. Conclusion : These results indicate that cobrotoxin has anti-cancer effects by inducing apoptosis.

• Tuberculosis and Respiratory Diseases
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• v.58 no.2
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• pp.152-159
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• 2005

Background : Exacerbations of chronic obstructive pulmonary disease (COPD) are thought to be associated with increased airway inflammation, and the $NF-{\kappa}B$ is known to be an indicator of cellular activation and of inflammatory mediator production. This study was undertaken to investigate the change of cytokine characteristics and $NF-{\kappa}B$ activity in induced sputum of COPD patients during exacerbation and recovery of the disease. Methods : Sputum induction was performed in 37 patients with COPD during exacerbation and during recovery and in 15 healthy subjects. Cell counts, levels of IL-6, IL-8 and $TNF-{\alpha}$ in induced sputum and NF-kB activity in macrophage of induced sputum were measured. Results : Patients with COPD showed significantly increased levels of IL-6, IL-8 and $TNF-{\alpha}$(p<0.01) and increased $NF-{\kappa}B$ activity in induced sputum(p<0.05) as compared with control subjects. Level of IL-8 during exacerbation of COPD decreased significantly during recovery(p<0.05). $NF-{\kappa}B$ activity and levels of IL-6 and $TNF-{\alpha}$ tended to be decreased during recovery, but not siginificantly. Conclusion : Activation of $NF-{\kappa}B$ and increased levels of IL-6, IL-8 and $TNF-{\alpha}$ were thought to be associated with pathogenesis and exacerbations of COPD.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.475-482
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• 2009

Rifampicin is a macrocyclic antibiotic which is used extensively for treatment against Mycobacterium tuberculosis and other mycobacterial infections. Recently, a number of studies have focused on the immune-regulatory effects of rifampicin. Therefore, we hypothesized that rifampicin may influence the TLR2 expression in LPS-activated RAW 264.7 cells. In this study, we determined that rifampicin suppresses LPS-induced TLR2 mRNA expression. The down-regulation of TLR2 expression coincided with decreased production of TNF-$\alpha$ Since NF-${\kappa}B$ is a major transcription factor that regulates genes for TLR2 and TNF-$\alpha$, we examined the effect of rifampicin on the LPS-induced NF-${\kappa}B$ activation. Rifampicin inhibited NF-${\kappa}B$ DNA-binding activity in LPS-activated RAW 264.7 cells, while it did not affect IKK$\alpha/\beta$ activity. However, rifampicin slightly inhibited the nuclear translocation of NF-${\kappa}B$ p65. In addition, rifampicin increased physical interaction between pregnane X receptor, a receptor for rifampicin, and NF-${\kappa}B$ p65, suggesting pregnane X receptor interferes with NF-${\kappa}B$ binding to DNA. Taken together, our results demonstrate that rifampicin inhibits LPS-induced TLR2 expression, at least in part, via the suppression of NF-${\kappa}B$ DNA-binding activity in RAW 264.7 cells. Thus, the present results suggest that the rifampicin-mediated inhibition of TLR2 via the suppression of NF-${\kappa}B$ DNA-binding activity may be a novel mechanism of the immune-suppressive effects of rifampicin.

• Korean Journal of Pharmacognosy
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• v.35 no.1 s.136
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• pp.92-97
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• 2004

Effect of AGI $({\alpha}-Glucosidase\;Inhibitor)-1120$, pine (Pinus densiflora) bark extract and Chaga mushroom (Inonotus obliquus) - and Chaga mushroom mycelium extracts on cellular $NF-{\kappa}B$ activation in malignant human keratinocytes (SCC-13) were evaluated to elucidate the possible correlation of $NF-{\kappa}B$ with antioxidant activity. The antioxidant activities of these natural products were examined in three different evaluation methods, i.e., lipid peroxidation value (POV) evaluation test, and 1,1diphenyl-2-picrylhydrazyl radical (DPPH) and nitric oxide (NO) scavenging test. In a cell-based $NF-{\kappa}B$ monitoring assay systern, all samples revealed the downregulatory profiles on the cellular $NF-{\kappa}B$ activity. AGI -1120 (1, 2 mg) and Chaga mushroom extract (0.05, 0.1 mg) downregulated the $NF-{\kappa}B$ activity in a dose-dependent manner. Chaga mushroom mycelium extract (5 mg) significantly inhibited the $NF-{\kappa}B$ activity (p<0.05). Although AGI-1120 and Chaga mushroom mycelium extract exhibited no antioxidant activities evaluated in pay, Chaga mushroom extract showed antioxidant in a dose-dependent manner at concentrations of $0.05{\sim}1$ mg. While AGI-1120 and Chaga mushroom extract possessed a relatively potential DPPH radical scavenging activity, the NO scavenging activity of Chaga mushroom extract $(SC_{50}:47\;{mu}g)$ was higher than the known antioxidant, vitamin C $(SC_{50}:77\;{mu}g)$. These results suggest that AGI-1120 and Chaga mushroom- and Chaga mushroom mycelium extracts may serve as an useful radical scavenging antioxidant agents with $NF-{\kappa}B$ inhibitory effect in human skin.

• Journal of Life Science
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• v.20 no.12
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• pp.1772-1776
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• 2010

Transcription factors Nrf2 and NF-${\kappa}B$ are important regulators of the innate immune response, and their cross-talks in inflammation have been reported. Previously, we demonstrated that gold(I)-compound auranofin, an inhibitor of NF-${\kappa}B$ signal, induced Nrf2 activation in human synovial cells and monocytic cells. To investigate whether the Nrf2 activation is involved in the mechanism of the auranofin-attenuated NF-${\kappa}B$ signaling, we examined the effects of Nrf2 knockdown on NF-${\kappa}B$ activation using rheumatic synovial cells. When the cells were transfected with a specific siRNA for Nrf2, the gene expression was perfectly blocked. However, the Nrf2 knockdown did not cancel the suppressive effect of auranofin on TNF-$\alpha$-induced $I{\kappa}B-{\alpha}$ degradation. Treatment with a specific siRNA for HO-1, which is a target of Nrf2 and plays a role in anti-inflammation, also did not affect the blocking activity of auranofin on $I{\kappa}B-{\alpha}$ degradation. In addition, auranofin-inhibited ICAM-1 expression was not restored by Nrf2 knockdown. These findings indicate that the activated Nrf2 and HO-1 are not associated with the suppressive action of auranofin on the pro-inflammatory cytokines-stimulated NF-${\kappa}B$ activation. This suggests that Nrf2/HO-1 and NF-${\kappa}B$ signals, which are regulated by auranofin, participate in the anti-inflammatory action of auranofin via independent pathways in rheumatic synovial cells.

• BMB Reports
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• v.35 no.3
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• pp.337-342
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• 2002

Many components that are derived from medicinal or dietary plants possess potential chemopreventive properties. Curcumin, a yellow coloring agent from turmeric (Curcuma longa Linn, Zingiberaceae), possesses strong antimutagenic and anticarcinogenic activities. In this study, we have found that curcumin inhibits the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced nuclear factor ${\kappa}B$ (NF-${\kappa}B$) activation by preventing the degradation of the inhibitory protein $I{\kappa}B{\alpha}$ and the subsequent translocation of the p65 subunit in cultured human promyelocytic leukemia (HL-60) cells. Alternatively, curcumin repressed the TPA-induced activation of NF-${\kappa}B$ through direct interruption of the binding of NF-${\kappa}B$ to its consensus DNA sequences. Likewise, the TPA-induced DNA binding of the activator protein-1 (AP-1) was inhibited by curcumin pretreatment.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.6
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• pp.922-928
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• 2012

Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)-butane] is one of the most abundant isothiocyanates in some cruciferous vegetables, especially broccoli. Sulforaphaene has been shown to exhibit many pharmacological activities, including anti-oxidant, anti-inflammatory and anti-microbial activities. However, the anti-skin photoaging effects of sulforaphane have not yet been reported. In the present study, we investigated the inhibitory effects of sulforaphane on MMP-1 and -3 expressions of the human dermal fibroblasts via various in vitro experiments and elucidated the pathways of inhibition. Western blot analysis and real-time PCR revealed sulfiraphane inhibited UVB-induced MMP-1 and -3 expressions in a dose-dependent manner. UVB strongly activated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity, which was determined by NF-${\kappa}B$ DNA binding activity. UVB-induced NF-${\kappa}B$ activation and MMP expression were completely blocked by sulforphane. These findings suggest that sulforaphane could prevent UVB-induced MMPs expressions through inhibition of NF-${\kappa}B$ activation.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.353-358
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• 2010

This study demonstrates the ability of magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, to inhibit LPS-induced expression of iNOS gene and activation of NF-${\kappa}B$/Rel in RAW 264.7 cells. Immunohisto-chemical staining of iNOS and Western blot analysis showed magnolol to inhibit iNOS gene expression. Reporter gene assay and electrophoretic mobility shift assay showed that magnolol inhibited NF-${\kappa}B$/Rel transcriptional activation and DNA binding, respectively. Since p38 is important in the regulation of iNOS gene expression, we investigated the possibility that magnolol to target p38 for its anti-inflammatory effects. A molecular modeling study proposed a binding position for magnolol that targets the ATP binding site of p38 kinase (3GC7). Direct interaction of magnolol and p38 was further confirmed by pull down assay using magnolol conjugated to Sepharose 4B beads. The specific p38 inhibitor SB203580 abrogated the LPS-induced NF-${\kappa}B$/Rel activation, whereas the selective MEK-1 inhibitor PD98059 did not affect the NF-${\kappa}B$/Rel. Collectively, the results of the series of experiments indicate that magnolol inhibits iNOS gene expression by blocking NF-${\kappa}B$/Rel and p38 kinase signaling.

• Biomolecules & Therapeutics
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• v.22 no.4
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• pp.288-294
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• 2014

Mangostenone F (MF) is a natural xanthone isolated from Garcinia mangostana. However, little is known about the biological activities of MF. This study was designed to investigate the anti-inflammatory effect and underlying molecular mechanisms of MF in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. MF dose-dependently inhibited the production of NO, iNOS, and pro-inflammatory cytokines (TNF-${\alpha}$, IL-6, and IL-$1{\beta}$) in LPS-stimulated RAW264.7 macrophages. Moreover, MF decreased the NF-${\kappa}B$ luciferase activity and NF-${\kappa}B$ DNA binding capacity in LPS-stimulated RAW264.7 macrophages. Furthermore, MF suppressed the NF-${\kappa}B$ activation by inhibiting the degradation of $I{\kappa}B{\alpha}$ and nuclear translocation of p65 subunit of NF-${\kappa}B$. In addition, MF attenuated the AP-1 luciferase activity and phosphorylation of ERK, JNK, and p38 MAP kinases. Taken together, these results suggest that the anti-inflammatory effect of MF is associated with the suppression of NO production and iNOS expression through the down-regulation of NF-${\kappa}B$ activation and MAPK signaling pathway in LPS-stimulated RAW264.7 macrophages.