A novel glucosamine derivative exerts anti-inflammatory actions via inhibition of nuclear factor-kappaB

Abstract

Glucosamine suppresses lipopolysaccharide (LPS)-induced upregulation of pro-inflammatory mediators both in vivo and in culture systems of mouse microglia or macrophage. In the present study, we show that the novel glucosamine derivative, 2-deoxy-2-[(o-methylbenzylidene)]-beta-glucopyranoside (NK-4), significantly reduced LPS-induced production of nitric oxide (NO) in BV2 microglia, RAW264.7 macrophage, and primary cultured peritoneal macrophages cells. NK-4 inhibited LPS-induced upregulation of inducible NO synthase (iNOS), cyclooxygenase-2, interleukin-6, tumor necrosis factor-alpha, and interleukin-1 beta in RAW264.7 cells in a time- and concentration-dependent manner. Furthermore, administering NK-4 significantly inhibited the induction of inflammatory cytokine mRNAs in the brains of LPS-injected mice. Although NK-4 inhibited LPS-induced nuclear factor-kappaB (NF-kappa B) activation, I kappa B-alpha degradation was not changed. Instead, NK-4 inhibited LPS-induced DNA-binding activity of NF-kappa B by suppressing p50 and c-Rel binding to NF-kappa B binding site of the iNOS promoter. (c) 2013 Elsevier Ireland Ltd. All rights reserved.