Inhibitory Action of Tsunokaori Tangor Peel on the Lipopolysaccharide-Induced Inflammatory Response in RAW 264.7 Macrophage Cells

  • Choi, Soo-Youn (Department of Life Science and Technology Innovation Center for Life Science, Cheju National University) ;
  • Hwang, Joon-Ho (Department of Life Science and Technology Innovation Center for Life Science, Cheju National University) ;
  • Ko, Hee-Chul (Department of Life Science and Technology Innovation Center for Life Science, Cheju National University) ;
  • Park, Soo-Young (Department of Life Science and Technology Innovation Center for Life Science, Cheju National University) ;
  • Kim, Gi-Ok (Hi-Tech Industry Development Institute) ;
  • Kim, Duck-Hee (R&D Center, Amore-Pacific Corporation) ;
  • Chang, Ih-Seop (R&D Center, Amore-Pacific Corporation) ;
  • Kwon, H.-Moo (Department of Medicine and Physiology, University of Maryland) ;
  • Kim, Se-Jae (Department of Life Science and Technology Innovation Center for Life Science, Cheju National University)
  • Published : 2006.04.30

Abstract

We evaluated the effects of extracts of Tsunokaori tangor peel on lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin $E_2\;(PGE_2)$ in RAW 264.7 cells. The ethyl acetate fraction of Tsunokaori tangor peel (EA-TTP) markedly inhibited the production of NO and $PGE_2$ in LPS-stimulated RAW 264.7 cells. Consistent with these findings, the expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins were down-regulated in a dose-dependent manner. Additionally, EA-TTP decreased the expression iNOS mRNA but not COX-2 mRNA. To determine the upstream signaling mechanism for the down-regulation of LPS-induced iNOS expression, we investigated the effect of EA-TTP on the degradation and re-synthesis of $I{\kappa}B{\alpha}$. EA-TTP dose-dependently delayed $I{\kappa}B{\alpha}$ degradation and increased $I{\kappa}B{\alpha}$ re-appearance following degradation, suggesting this as the mechanism by which EA-TTP suppressed iNOS gene expression. The EA-TTP also dose-dependently reduced the expression of the cellular stress-response protein heme oxygenase-1, and inhibited the LPS-induced sustained activation of extracellar signal-regulated kinase (ERK).

Keywords

References

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