Imperatorin attenuates LPS-induced inflammation by suppressing NF-κB and MAPKs activation in RAW 264.7 macrophages

Inflammation. 2012 Dec;35(6):1764-72. doi: 10.1007/s10753-012-9495-9.

Abstract

Imperatorin is a type of coumarin compound with antibacterial and antiviral activities. In the present study, we examined the anti-inflammatory effects of imperatorin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages by investigating its impact on the production and expression of cytokines and the major signal-transduction pathways. We found that imperatorin downregulated LPS-induced levels of TNF-α, IL-1β, and IL-6 in RAW 264.7 macrophages in a concentration-dependent manner, and it significantly inhibited expression of TNF-α and IL-6 (P < 0.05 or P < 0.01). The phosphorylation of mitogen-activated protein kinases and nuclear factor-kappaB (NF-κB) p65 protein were analyzed by western blotting. In RAW 264.7 macrophages treated with 1 mg/L of LPS, imperatorin significantly inhibited p38 and Jun N-terminal kinase phosphorylation protein expression. However, there was no significant change in p-ERK. Furthermore, imperatorin also inhibited NF-κB translocation into the nucleus through blockage of IκBα phosphorylation and degradation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Cell Line
  • Cell Survival
  • Enzyme Activation / drug effects
  • Furocoumarins / pharmacology*
  • I-kappa B Kinase / metabolism
  • Inflammation / drug therapy*
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Interleukin-1beta / biosynthesis
  • Interleukin-1beta / drug effects
  • Interleukin-1beta / metabolism
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lipopolysaccharides
  • Macrophages / immunology*
  • Mice
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / drug effects
  • NF-kappa B / metabolism*
  • Phosphorylation / drug effects
  • Protein Transport
  • Transcription Factor RelA / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Inflammatory Agents
  • Furocoumarins
  • Inflammation Mediators
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Rela protein, mouse
  • Transcription Factor RelA
  • Tumor Necrosis Factor-alpha
  • I-kappa B Kinase
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • imperatorin