Inhibitory Effect of Amentoflavone of Selaginella Tamariscina on MMP-9 Expression through NF-${\kappa}$B and AP-1 in Macrophage Raw 264.7 cells

  • Ahn, Byung-Tae (Cardiovascular Medical Research Center and Department of Diagnostics, Dongguk University) ;
  • Shin, Sung-Ahn (Cardiovascular Medical Research Center and Department of Diagnostics, Dongguk University) ;
  • Kim, Jun-Gi (Department of Pathology, College of Korean Medicine, Dongguk University) ;
  • Park, Won-Hwan (Cardiovascular Medical Research Center and Department of Diagnostics, Dongguk University)
  • Published : 2007.02.25

Abstract

The French paradox has been attributed to the antioxidant properties of flavonoids present in the red wine. Amentoflavone(AF) is a bi-flavonoid compound with anti-fungal and anti-inflammatory activities. We isolated AF from Selaginella tamariscina, and studied its effects on nuclear factor-B(NF-B)-mediated MMP-9 gene expression in RAW264.7 cells. AF blocked the lipopolysaccharide(LPS)-induced expression of MMP-9. Zymographic and immunoblot analyses showed that AF suppressed LPS-induced MMP-9 expression in a dose-dependent manner. To clarify the mechanistic basis for its inhibition of MMP-9 induction, we examined the effect of AF on the transactivation of MMP-9 gene by luciferase reporter activity using -1.59 kb flanking region. AF potently suppressed the reporter gene activity. This inhibition was characterized by down-regulation of MMP-9, which was transcriptionally regulated at NF-B site and activation protein-1 (AP-1) site in the MMP-9 promoter, two important nuclear transcription factors that are involved in MMP-9 expression. These findings indicate the efficacy of AF in inhibiting MMP-9 expression through the transcription factors NF-B and AP-1 on LPS-induced RAW264.7 cells.

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