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The Pharmaceutical Society of Korea (대한약학회)
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Flavonoids Differentially Modulate Nitric Oxide Production Pathways in Lipopolysaccharide-Activated RAW264.7 Cells

  • Kim Ae Ra (College of Pharmacy, Pusan National University) ;
  • Cho Jae Youl (School of Biotechnology and Bioengineering, Kangwon National University) ;
  • Zou Yani (College of Pharmacy, Pusan National University) ;
  • Choi Jae Sue (Faculty of Food Science and Biotechnology, Pukyong National University) ;
  • Chung Hae Young (College of Pharmacy, Pusan National University)
  • Published : 2005.03.01
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Abstract

Naturally occurring flavonoids are known to modulate various inflammatory and immune processes. Based on structural property, in this study, molecular mechanism of flavonoids in modulating nitric oxide (NO) production and its signaling pathway were investigated using lipopolysaccharide (LPS)-activated RAW264.7 cells. Although flavonol-typed flavonoids (kaempferol and quercetin) more potently scavenged reactivity of nitric oxide ($\cdot$NO) as well as peroxynitrite (ONOO$\kappa$) than isoflavones (genistein and genistin), kaempferol, quercetin and genistein showed a little difference in inhibition of both inducible NO synthase expression and NO production, with IC$_{50}$ values of 13.9, 20.1 and 26.8 $\mu$M. However, there was a striking pattern related to structural feature in modulation of LPS-mediated signaling pathways. Thus, flavonols only inhibited transcription factor AP-1 activation, whereas isoflavones suppressed the DNA binding activation of NF-$\kappa$B and C/EBP$\beta$. Therefore, these data suggest that structural feature may be linked to decide drugs target molecule in LPS-mediated signaling pathways, rather than its potency.

Keywords

References

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