• Molecules and Cells
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• 제20권3호
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• pp.364-370
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• 2005

We show that sulforaphane inhibits osteoclastogenesis in the presence of macrophage colony-stimulating factor (M-CSF) and receptor for activation of nuclear factor-${\kappa}B$ ligand (RANKL) in osteoclast (OC) precursors. Sulforaphane, an aliphatic isothiocyanate, is a known cancer chemo-preventative agent with anti-oxidative properties. Nuclear factor-${\kappa}B$ (NF-${\kappa}B$) is a critical transcription factor in RANKL-induced osteoclastogenesis, and electrophoretic mobility shift assays (EMSAs) and assay of NF-${\kappa}B$-mediated secreted alkaline phosphatase (SEAP) revealed that sulforaphane selectively inhibited NF-${\kappa}B$ activation induced by RANKL. Inhibition may involve interaction of sulforaphane with thiol groups, since it was prevented by reducing agents.

• The Korean Journal of Physiology and Pharmacology
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• 제21권4호
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• pp.449-456
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• 2017

Beauvericin (BEA), a cyclic hexadepsipeptide produced by the fungus Beauveria bassiana, is known to have anti-cancer, anti-inflammatory, and anti-microbial actions. However, how BEA suppresses macrophage-induced inflammatory responses has not been fully elucidated. In this study, we explored the anti-inflammatory properties of BEA and the underlying molecular mechanisms using lipopolysaccharide (LPS)-treated macrophage-like RAW264.7 cells. Levels of nitric oxide (NO), mRNA levels of transcription factors and the inflammatory genes inducible NO synthase (iNOS) and interleukin (IL)-1, and protein levels of activated intracellular signaling molecules were determined by Griess assay, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), luciferase reporter gene assay, and immunoblotting analysis. BEA dose-dependently blocked the production of NO in LPS-treated RAW264.7 cells without inducing cell cytotoxicity. BEA also prevented LPS-triggered morphological changes. This compound significantly inhibited nuclear translocation of the $NF-{\kappa}B$ subunits p65 and p50. Luciferase reporter gene assays demonstrated that BEA suppresses MyD88-dependent NF-${\kappa}B$ activation. By analyzing upstream signaling events for $NF-{\kappa}B$ activation and overexpressing Src and Syk, these two enzymes were revealed to be targets of BEA. Together, these results suggest that BEA suppresses $NF-{\kappa}B$-dependent inflammatory responses by suppressing both Src and Syk.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book I
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• pp.780-803
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• 2003

Exposure of skin cells, particularly keratinocytes to various nuclear factor-kappaB ($\textrm{NF}_{-{\kappa}}\textrm{B}$) activators [e.g. tumor necrosis factor-$\alpha$, interleukin-1, lipopolysaccharides, and ultraviolet light] leads to phosphorylation and degradation of the inhibitory protein, $\textrm{I}_{{\kappa}}\textrm{B}$. Liberated $\textrm{NF}_{-{\kappa}}\textrm{B}$ is translocated into the nucleus where it can change or alter expression of target genes, resulting in the secretion of extracellular signaling molecules including melanotrophic factors affecting melanocyte. In order to demonstrate the possible role of $\textrm{NF}_{-{\kappa}}\textrm{B}$ activation on the synthesis of melanotrophic factors from the keratinocytes, the activities of $\textrm{NF}_{-{\kappa}}\textrm{B}$ induced by melanogenic inhibitors (MIs) were determined in human HaCaT keratinocytes transfected with $\textrm{pNF}_{-{\kappa}}\textrm{B}$-SEAP-NPT plasmid. Transfectant cells released the secretory alkaline phosphatase (SEAP) as a transcription reporter in response to the $\textrm{NF}_{-{\kappa}}\textrm{B}$ activity and contain the neomycin phosphotransferase (NPT) gene for the dominant selection marker for geneticin resistance. MIs such as niacinamide, kojic acid, hydroquinone, resorcinol, arbutin, and glycolic acid were preincubated with transfectant HaCaT cells for 3 h and then ultraviolet B (UVB) was irradiated. $\textrm{NF}_{-{\kappa}}\textrm{B}$ activation was measured with the SEAP reporter gene assay using a fluorescence detection method. Of the Mis tested, kojic acid ($IC_{50}$/ = 60 $\mu$M) was found to be the most potent inhibitor of UVB-upregulating $\textrm{NF}_{-{\kappa}}\textrm{B}$ activation in transfectant HaCaT cells, which is followed by niacinamide ($IC_{50}$/= 540 $\mu$M). Pretreatment of the transfectant HaCaT cells with the Mis, especially kojic acid and niacinamide, effectively lowered $\textrm{NF}_{-{\kappa}}\textrm{B}$ binding measured by electrophoretic mobility shift assay. Furthermore, these two inhibitors remarkably reduced the secretion level of IL-6, one of melanotrophic factors, triggered by UV-radiation of the HaCaT cells. These observations suggest that Mis working at the in vivo level might act partially through the modulation of the synthesis of melanotrophic factors in keratinocyte.

• Biomolecules & Therapeutics
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• 제23권5호
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• pp.428-433
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• 2015

Acetylshikonin, a natural naphthoquinone derivative compound, has been used for treatment of inflammation and cancer. In the present study, we have investigated whether acetylshikonin could regulate the NF-${\kappa}B$ signaling pathway, thereby leading to suppression of tumorigenesis. We observed that acetylshikonin significantly reduced proliferation of several cancer cell lines, including human pancreatic PANC-1 cancer cells. In addition, acetylshikonin inhibited phorbol 12-myristate 13-acetate (PMA) or tumor necrosis-${\alpha}$ (TNF-${\alpha}$)-induced NF-${\kappa}B$ reporter activity. Proteome cytokine array and real-time RT-PCR results illustrated that acetylshikonin inhibition of PMA-induced production of cytokines was mediated at the transcriptional level and it was associated with suppression of NF-${\kappa}B$ activity and matrix metalloprotenases. Finally, we observed that an exposure of acetylshikonin significantly inhibited the anchorage-independent growth of PANC-1 cells. Together, our results indicate that acetylshikonin could serve as a promising therapeutic agent for future treatment of pancreatic cancer.

• Journal of Magnetics
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• 제6권2호
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• pp.66-69
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• 2001

The actual magnetic induction waveform of cores in electrical machines is not sinusoidal i.e. higher harmonics are always included. Thus the core loss in actual electrical machines is different from the core loss which is measured by the standard method, because the waveform of magnetic induction should be sinusoidal in the standard testing method. Core loss analysis under higher harmonic induction is always important in electric machine design. In this works we measured the core loss when a hysteresis loop has only one period of an ac minor loop of higher harmonic frequency, depending on the position of the ac minor loop of relative to the fundamental harmonic frequency. From this experiment, the core loss P(B/sub 0/f/sub 0/, B/sub h/, nf/sub 0/)) under a higher harmonic magnetic induction B/sub h/ could be expressed by the linear combination the core loss at fundamental harmonic frequency P/sub c/(B/sub 0/, f/sub 0/), the core loss of ac minor loop at zero induction region of the major hysteresis loop P/sub cL/ (B/sub h/, nf/sub 0/), and the core loss of an ac minor loop in the high induction region of the major hysteresis loop P/sub cH/ (B/sub h/, nf/sub 0/) i.e., P/sub c/, (B/sub 0/, f/sub 0/, B/sub h/, nf/sub 0/)=P/sub c/ (B/sub 0/, f/sub 0/,)+(n-1)[k₁(B/sub 0/) P/sub cL/ (B/sub h/, nf/sub 0/)+(1-k₁(B/sub 0/)) P/sub cH/ (B/sub h/, nf/sub 0/)]. This will be useful formula for electrical machine designers and one of effective methods to predict core loss including higher harmonic induction.

• 생약학회지
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• 제35권1호통권136호
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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.

• 한국식품영양과학회지
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• 제33권10호
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• pp.1594-1600
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• 2004

다양한 생리활성을 지닌 천연물 겨우살이와 칡뿌리 추출물의 인체피부조직세포에서 NF-$textsc{k}$B촬성에 대한조절효과와 이들 추출물의 지질 과산화물 생성 억제 및 라디칼 소거활성, reducing power와 관련된 항산화적 활성을 조사하였다. 본 실험 에 사용한 모든 시료들은 세포독성을 보이지 않는 수준에서 NF-$textsc{k}$B 활성 을 억 제 했다. 칡뿌리 추출물은 0.5 mg 농도에서 35%로 vitamin C 10 mM(8.8 mg,53%)과 함께 유의적인 NF-$textsc{k}$B활성 억제효과를 보였다(p<0.05).또한 칡뿌리 추출물은 겨우살이 추출물보다 상대적으로 더 높은 NF-$textsc{k}$B활성 억제 효과를 보였다. 겨우살이 추출물의 NF-$textsc{k}$B활성 억제 효과는 10%로 낮았지 만,지질 과산화물에 대한 항산화 효과는 5 mg 이상의 농도에서 63% 이상으로 칡뿌리 추출물보다 높았다. 겨우살이와 칡뿌리 추출물은 동일 농도 10 mg에서 vitamin C의 항산화 효과, 48%보다 각각 유의적으로 높은 56%와 75%의 항산화 활성을 보였다. 라디칼 소거활성에 대하여 칡뿌리 추출물이 겨우살이 추출물보다 동일농도에서 더 강한 소거활성을 나타냈다. 잘 알려진 항산화제 vitamin C와 비교해 볼 때, DPPH test에서 이 두 추출물은 vitamin C만큼 강한 라디칼 소거활성을 보이지는 않았다. 그러나 NO test에서 칡 뿌리 추출물의 SCn은 88 Ug으로 vitamin C($SC_{50}$/, 77 $\mu$g)만큼 강한 항산화 활성을 보였다(p<0.05). 칡뿌리 추출물의 항산화 활성은 reducing power측정 에서도 겨우살이 추출물보다 높게 나타났으나, vitamin C의 환원력보다는 매우 낮은 활성을 보였다. 본 연구의 전체 결과를 통해서, 강한 라디칼 소거활성을 지닌 칡뿌리 추출물과 상대적으로 높은 지질 과산화 억제 효과를 보인 겨우살이 추출물은 천연 항산화제로 제안될 수 있는 것으로 판단되었다. 또한 vitamin C와 칡뿌리 추출물의 결과처럼 천연 추출물의 인체피부조직세포에서 NF-$textsc{k}$B활성 조절 효과의 일부는 이들 천연 추출물이 지닌 라디칼 소거활성 또는reducing power의 항산화 활성의 역할에 의한 것으로 제안되었다.

• Journal of Microbiology and Biotechnology
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• 제30권4호
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• pp.490-496
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• 2020

Consumption of anti-inflammatory nutraceuticals may help treat or prevent inflammation-related illnesses such as diabetes, cardiovascular disease, and cancer. This study evaluated the effect of Croton hirtus L'Hér extract (CHE) on lipopolysaccharide (LPS)-induced nitric oxide (NO) production and nuclear factor kappa-B (NF-κB) signaling cascades. CHE significantly suppressed LPS-induced NO production and inducible nitric oxide synthase (iNOS) expression in RAW264.7 macrophages, although cyclooxygenase (COX)-2 expression was not affected. CHE also suppressed LPS-induced IκB kinase (IKK), IκB, and p65 phosphorylation in RAW264.7 cells. Western blot and immunofluorescence assays of cytosol and nuclear p65 and the catalytic subunit of NF-κB showed that CHE suppressed LPS-induced p65 translocation from the cytosol to the nucleus. CHE also suppressed LPS-induced Interleukin (IL)-6 and tumor necrosis factor (TNF)-α production in RAW264.7 cells. These results suggest that CHE prevents NO-mediated inflammation by suppressing NF-κB and inflammatory cytokines.

• BMB Reports
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• 제40권3호
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• pp.341-348
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• 2007

Herpesvirus saimiri (HVS), a member of the $\delta$-herpesvirus family, encodes an oncoprotein called Saimiri Transforming Protein (STP) which is required for lymphoma induction in non-human primates. Previous study has shown that STP-C, an oncoprotein of HVS, activates NF-$\kappa$B signaling pathway. However, the detailed mechanism of STP-Cmediated NF-$\kappa$B activation has not been reported yet. We first report that STP-C interacts with TRAF6 protein in vivo and in vitro and further investigation shows that $Glu_{12}$ residue of STP-C is critical for binding to TRAF6. Introduction of ubiquitin together with STP-C augments NF-$\kappa$B activity compared to that of STP-C expression alone. STP-C expression further induces ubiquitination of endogenous TRAF6. In addition, either a deubiquitination enzyme, CYLD or a dominant negative E2-conjugation enzyme reduced NF-$\kappa$B activity in spite of the presence of STP-C, supporting that the interaction between STP-C and TRAF6 induces ubiquitination of TRAF6. NF-$\kappa$B activation by STP-C through the ubiquitinated TRAF6 causes the increased production of IL-8, an inflammatory chemokine and the enhanced expression of costimulatory molecule ICAM, which might ultimately contribute cellular transformation by the exposure of HVS-infected cells with inflammatory microenvironment and chronic activation.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 춘계학술대회 논문집
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• pp.25-26
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• 2003

There is increasing interest in the involvement of transcription factors, such as of the transcription factor NF-kB (nuclear factor-kB), in the pathogenesis of various diseases. The involvement ofNF-kB is especially of interest as it is activated by oxidative stress and its activation can be modulated by antioxidant compounds. (omitted)