Inhibitory Effects of JEUD-38, a New Sesquiterpene Lactone from Inula japonica Thunb, on LPS-Induced iNOS Expression in RAW264.7 Cells

Inflammation. 2015;38(3):941-8. doi: 10.1007/s10753-014-0056-2.

Abstract

We isolated JEUD-38, a new sesquiterpene lactone from Inula japonica Thunb. JEUD-38 dramatically attenuated lipopolysaccharide (LPS)-induced nitric oxide (NO) production. Consistent with this finding, the protein expression of inducible nitric oxide synthase (iNOS) was blocked by JEUD-38 in a concentration-dependent manner. To elucidate the mechanism, we examined the effect of JEUD-38 on LPS-stimulated nuclear factor-κB (NF-κB) nuclear translocation, inhibitory factor-κB (IκB) phosphorylation, and degradation. JEUD-38 reduced the translocation of p65, via abrogating IκB-α phosphorylation and degradation. In addition, JEUD-38 inhibited LPS-stimulated phosphorylation of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Since iNOS as well as the upstream NF-κB and MAPKs are known to be closely involved in inflammation, these results suggest that JEUD-38 is a promising candidate for prevention and therapy of inflammatory diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Cell Line
  • Humans
  • I-kappa B Proteins / metabolism
  • Inflammation / immunology
  • Inflammation / prevention & control
  • Inula / metabolism
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lactones / pharmacology*
  • Lipopolysaccharides
  • Macrophages / enzymology
  • Macrophages / metabolism*
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase Type II / biosynthesis*
  • Phosphorylation / drug effects
  • Plant Extracts / pharmacology
  • Proteolysis / drug effects
  • Sesquiterpenes / pharmacology
  • Sesquiterpenes, Eudesmane / pharmacology*
  • Transcription Factor RelA / metabolism
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • 1-oxo-4aH-eudesma-5(6),11(13)-dien-12,8-olide
  • Anti-Inflammatory Agents
  • I-kappa B Proteins
  • Lactones
  • Lipopolysaccharides
  • Plant Extracts
  • RELA protein, human
  • Sesquiterpenes
  • Sesquiterpenes, Eudesmane
  • Transcription Factor RelA
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases