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Anti-inflammatory Effects of Amentoflavone on Modulation of Signal Pathways in LPS-stimulated RAW264.7 Cells

  • Lee, Eun-Jung (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Shin, So-Young (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Kim, Jin-Kyoung (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University) ;
  • Woo, Eun-Rhan (College of Pharmacy, Chosun University) ;
  • Kim, Yang-Mee (Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University)
  • Received : 2012.05.12
  • Accepted : 2012.05.26
  • Published : 2012.09.20

Abstract

Amentoflavone is naturally occurring bioflavonoid that is found in a number of plants. In this paper, the anti-inflammatory activity of amentoflavone in LPS-stimulated macrophages and its mode of action were examined. Using LPS-stimulated RAW264.7 macrophage cells, we found that amentoflavone exerted anti-inflammatory activities through inhibition of nitric oxide (NO) production and tumor necrosis factor (TNF)-${\alpha}$ and macrophage inflammatory protein (MIP)-2 secretion. Amentoflavone (1.0-20 ${\mu}M$) gradually inhibited nitrite production without cytotoxicity. Amentoflavone (1.0 and 10 ${\mu}M$) effectively suppressed both TNF-${\alpha}$ and MIP-2 cytokine release from LPS-stimulated RAW264.7 cells. The expression of mIL-$1{\beta}$ and mMIP-2 cytokine mRNAs was completely inhibited while expression of mMIP-1 was effectively suppressed and mTNF-${\alpha}$ expression was slightly inhibited by 10 ${\mu}M$ amentoflavone. We also demonstrated that the innate immune response to amentoflavone involves the toll-like receptor (TLR) and mitogen-activated protein kinase (MAPK) pathways. LPS-induced upregulation of p38 MAPK phosphorylation was significantly reduced by 10 ${\mu}M$ amentoflavone. These results suggest that amentoflavone exhibits effective anti-inflammatory activities through regulation of TLR4 and phosphorylation of p38 MAPKs.

Keywords

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