Anti-inflammation effect of methyl salicylate 2-O-β-D-lactoside on adjuvant induced-arthritis rats and lipopolysaccharide (LPS)-treated murine macrophages RAW264.7 cells

Int Immunopharmacol. 2015 Mar;25(1):88-95. doi: 10.1016/j.intimp.2015.01.024. Epub 2015 Jan 28.

Abstract

Methyl salicylate 2-O-β-D-lactoside (MSL) is a derivative of natural salicylate isolated from Gaultheria yunnanensis (Franch.) Rehder, which is widely used for treating rheumatoid arthritis (RA), swelling and pain. The aim of the present study was to investigate the effect of MSL on the progression of adjuvant-induced arthritis (AIA) in rat in vivo and explore the anti-inflammatory effects and mechanism of MSL in lipopolysaccharide (LPS)-treated murine macrophages RAW264.7 cells in vitro. Our results showed that MSL significantly inhibited the arthritis progression in AIA rats, decreasing the right hind paw swelling and ankle diameter, attenuating histopathological changes and suppressing the plasma levels of TNF-α and IL-1β in AIA rats. Besides, MSL had potent anti-inflammatory effects on the LPS-activated RAW264.7. MSL dose-dependently inhibited the activity of COX-1, and COX-2. Moreover, MSL prominently inhibited LPS-induced activation of MAPK in RAW264.7 cells by blocking phosphorylation of p38 and ERK. Our study suggests that MSL may be effective in the treatment of inflammatory diseases by inhibiting the pro-inflammatory cytokine production and regulating the MAPK signal pathway.

Keywords: Adjuvant-induced arthritis; Cyclooxygenase; MAPK signaling pathway; Methyl salicylate 2-O-β-D-lactoside; Prostaglandin E(2).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / immunology
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology
  • Cell Line
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Disease Progression
  • Gaultheria / immunology*
  • Humans
  • Interleukin-1beta / metabolism
  • Lactose / administration & dosage
  • Lactose / analogs & derivatives*
  • Lipopolysaccharides / immunology
  • MAP Kinase Signaling System / drug effects
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Male
  • Mice
  • Phosphorylation / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Salicylates / administration & dosage*
  • Tumor Necrosis Factor-alpha / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Inflammatory Agents
  • Interleukin-1beta
  • Lipopolysaccharides
  • Salicylates
  • Tumor Necrosis Factor-alpha
  • methyl salicylate 2-O-lactoside
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • p38 Mitogen-Activated Protein Kinases
  • Lactose