Arctigenin inhibits lipopolysaccharide-induced iNOS expression in RAW264.7 cells through suppressing JAK-STAT signal pathway

Int Immunopharmacol. 2011 Aug;11(8):1095-102. doi: 10.1016/j.intimp.2011.03.005. Epub 2011 Mar 21.

Abstract

Arctigenin has been demonstrated to have an anti-inflammatory function, but the precise mechanisms of its action remain to be fully defined. In the present study, we determined the effects of arctigenin on lipopolysaccharide (LPS)-induced production of proinflammatory mediators and the underlying mechanisms involved in RAW264.7 cells. Our results indicated that arctigenin exerted its anti-inflammatory effect by inhibiting ROS-dependent STAT signaling through its antioxidant activity. Arctigenin also significantly reduced the phosphorylation of STAT1 and STAT 3 as well as JAK2 in LPS-stimulated RAW264.7 cells. The inhibitions of STAT1 and STAT 3 by arctigenin prevented their translocation to the nucleus and consequently inhibited expression of iNOS, thereby suppressing the expression of inflammation-associated genes, such as IL-1β, IL-6 and MCP-1, whose promoters contain STAT-binding elements. However, COX-2 expression was slightly inhibited at higher drug concentrations (50 μM). Our data demonstrate that arctigenin inhibits iNOS expression via suppressing JAK-STAT signaling pathway in macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Cell Line
  • Cell Survival / drug effects
  • Chemokine CCL2 / antagonists & inhibitors
  • Chemokine CCL2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Drug Interactions
  • Furans / pharmacology*
  • Interleukin-1beta / antagonists & inhibitors
  • Interleukin-1beta / genetics
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / genetics
  • Janus Kinase 2 / antagonists & inhibitors*
  • Janus Kinase 2 / metabolism
  • Lignans / pharmacology*
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / metabolism
  • Mice
  • Mitochondrial Proteins / antagonists & inhibitors
  • Mitochondrial Proteins / metabolism
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Phosphorylation / drug effects
  • Promoter Regions, Genetic / drug effects
  • STAT1 Transcription Factor / antagonists & inhibitors*
  • STAT1 Transcription Factor / metabolism
  • STAT3 Transcription Factor / antagonists & inhibitors*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects

Substances

  • Anti-Inflammatory Agents
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Furans
  • Interleukin-1beta
  • Interleukin-6
  • Lignans
  • Lipopolysaccharides
  • Membrane Proteins
  • Mitochondrial Proteins
  • Romo1 protein, mouse
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • Stat1 protein, mouse
  • Stat3 protein, mouse
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Jak2 protein, mouse
  • Janus Kinase 2
  • arctigenin