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KMID : 0603820080140030147
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Journal of Experimental & Biomedical Science
2008 Volume.14 No. 3 p.147 ~ p.155
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Taxifolin Inhibited the Nitric Oxide Production and Expression of Pro-inflammatory Cytokine mRNA in Lipopolysaccharide-stimulated RAW264.7 Cells
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Rhee Man-Hee
Mehari Endale
Kamruzzaman S.M.
Park Hwa-Jin
You Myung-Jo
Cho Jae-Youl
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Abstract
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In previous works, we found that solvent extract of Opuntia humifusa Raf., a member of the lactaceae family, displayed potent anti-oxidative and anti-inflammatory activities. Thus, all solvent fractions, except for the water layer, showed potent scavenging effects. According to activity-guided fractionation, one of active radical scavenging principles in the ethyl acetate fraction was found to be taxifolin. In this study, we investigated whether taxifolin showed anti-oxidative activity. In addition, taxifolin modulated nitric oxide (NO) release and the expression of pro-inflammatory cytokine mRNA such as interleukin-1β (IL-1β), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and TNF-α. Taxifolin showed potent anti-oxidant activity with the IC?? of 8.5±1.4 and 9.3±1.0 μM using xanthine/xanthine oxidase (XO) assay and 2,2-Diphenyl-lpicrylhydrazyl radical (DPPH) assay, respectively. We next determined the role of taxifolin on the immunomodulating activity using murine macrophage cell line RAW264.7 cells. Taxifolin dosedependently inhibited NO production in lipopolysaccharide (LPS)-activated RAW264.7. It also significantly blocked the expression of inducible NO synthase (iNOS) mRNA in the LPS-stimulated RAW264.7 cells. In addition, taxifolin potently suppressed the expression of IL-1β, IL-6 and GM-CSF mRNA in LPS-activated RAW264.7 cells, but not that of TNF-α. Moreover, taxifolin significantly inhibited the transcriptional activity of nuclear factor-κB (NF-κB) and activator protein -1 (AP-1). These results suggest that taxifolin may downregulate inflammatory iNOS, IL-1β, IL-6 and GM-CSF gene expressions through inhibition of NF-K and AP-1 activation in LPS-stimulated RAW264.7 cells.
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KEYWORD
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Taxifolin, Opuntia humifusa Raf, Anti-oxidative activity, Anti-inflammatory activity, Nitric oxide, Pro-inflammatory cytokines
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