Sesquiterpene lactone fraction from Artemisia khorassanica inhibits inducible nitric oxide synthase and cyclooxygenase-2 expression through the inactivation of NF-κB

Immunopharmacol Immunotoxicol. 2010 Dec;32(4):688-95. doi: 10.3109/08923971003677808. Epub 2010 Mar 17.

Abstract

Objective: Members of the Artemisia genus (Astraceae) are important medicinal plants throughout the world. Here, we prepared a sesquiterpene lactone fraction from Artemisia khorassanica (SLAK) and evaluated its effect on inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) expression, and nuclear factor-κB (NF-κB) activity.

Methods: The effects of SLAK on lipopolysaccharide (LPS)-induced NO, prostaglandin E(2) (PGE(2)), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) production was evaluated in mouse macrophage J774A.1 cells. Moreover, we evaluated SLAK modulation of iNOS and COX-2 enzyme expression by western blot analysis.

Results: Our data revealed that SLAK (10-100 μg/mL), in a dose-dependent manner, inhibits NO, PGE(2), TNF-α, and IL-1β production induced by LPS in the J774A.1 cells. These data were consistent with the modulation of iNOS and COX-2 expressions. It was also showed that SLAK suppresses the iNOS and COX-2 enzyme expression through the inhibition of NF-κB activity.

Conclusion: In this study, we demonstrated that SLAK inhibits the production of NO, PGE2, TNF-α, and IL-1β in LPS-stimulated macrophages. This anti-inflammatory effect possibly occurs by inhibiting iNOS and COX-2 expression via the inactivation of NF-κB pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Artemisia / chemistry*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cyclooxygenase 2 / metabolism*
  • Dinoprostone / metabolism
  • Dose-Response Relationship, Drug
  • Gene Expression / drug effects
  • Interleukin-1beta / metabolism
  • Lactones / chemistry
  • Lactones / isolation & purification
  • Lactones / pharmacology*
  • Lipopolysaccharides / pharmacology
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Magnetic Resonance Spectroscopy
  • Mice
  • NF-kappa B / metabolism*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism*
  • Plant Components, Aerial / chemistry
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology*
  • Spectrophotometry, Infrared
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-1beta
  • Lactones
  • Lipopolysaccharides
  • NF-kappa B
  • Sesquiterpenes
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Dinoprostone