Koumine Attenuates Lipopolysaccaride-Stimulated Inflammation in RAW264.7 Macrophages, Coincidentally Associated with Inhibition of NF-κB, ERK and p38 Pathways

Int J Mol Sci. 2016 Mar 22;17(3):430. doi: 10.3390/ijms17030430.

Abstract

Medicinal herbal plants have been commonly used for intervention of different diseases and health enhancement worldwide. Koumine, an alkaloid monomer found abundantly in Gelsemium plants, can be effectively used as an anti-inflammatory medication. In this study, the mechanisms associated with the preventative effect of koumine on lipopolysaccharide (LPS)-mediated inflammation in RAW264.7 macrophages were investigated. Koumine induced a decrease in the level of inducible nitric oxide synthase (iNOS) protein, concomitant reduction in the production of nitric oxide (NO) and reduction of the levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and IL-1β. Furthermore, koumine decreased the phosphorylation of p65 and inhibited nuclear factor κ Bα (IκBα) proteins, resulting in lower production of nuclear factor (NF)-κB transactivation. Koumine also induced a decrease in the phosphorylation of extracellular-signal-regulated kinases (ERK) and p38 in RAW264 cells. In conclusion, these findings reveal that koumine decreases the productions of pro-inflammatory mediators though the suppression of p38 and ERK MAPK phosphorylation and the inhibition of NF-κB activation in RAW264.7 cells.

Keywords: LPS; NF-κB; NO; RAW264.7 macrophages; iNOS; inflammation; koumine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Cell Line
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Indole Alkaloids / pharmacology*
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / toxicity
  • MAP Kinase Signaling System*
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • NF-kappa B / metabolism*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Indole Alkaloids
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • koumine
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Extracellular Signal-Regulated MAP Kinases
  • p38 Mitogen-Activated Protein Kinases