Agrimonolide from Agrimonia pilosa suppresses inflammatory responses through down-regulation of COX-2/iNOS and inactivation of NF-κB in lipopolysaccharide-stimulated macrophages

Phytomedicine. 2016 Jul 15;23(8):846-55. doi: 10.1016/j.phymed.2016.03.016. Epub 2016 Apr 22.

Abstract

Background: Agrimonolide from Agrimonia pilosa showed a strong anti-inflammatory activity, and the present study aims to reveal potential mechanisms on molecular level explaining its anti-inflammatory effect.

Hypothesis/purpose: To investigate the mechanism of anti-inflammatory activity of agrimonolide.

Study design: Anti-inflammatory activity of agrimonolide in cells was applied.

Methods: Anti-inflammatory activity of agrimonolide isolated from Agrimonia pilosa was evaluated using lipopolysaccharide (LPS) stimulated RAW 264.7 cell models. The productions of IL-1β, IL-6, TNF-α and NO were determined by ELISA and nitrite analysis, respectively. The expressions of iNOS and COX-2 were measured by western blotting and RT-PCR analysis.

Results: The pre-treatment with agrimonolide significantly reduced the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), as well as attenuated the expression of iNOS and COX-2 in LPS-stimulated macrophages. Furthermore, agrimonolide inhibited the activation of JNK and p38 MAPKs and decreased the activation of JAK-STAT and NF-κB in LPS-stimulated macrophages.

Conclusion: The present study suggested that agrimonolide exerted anti- inflammatory activity, at least in part, via suppressing LPS-induced activation of JAK-STATs and p38 MAPKs signaling pathway.

Keywords: Agrimonolide; Anti-inflammation; Macrophages; Mechanism.

MeSH terms

  • Agrimonia / chemistry*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Survival / drug effects
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Cytokines / antagonists & inhibitors
  • Down-Regulation / drug effects
  • Enzyme Inhibitors / pharmacology
  • Isocoumarins / pharmacology*
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects*
  • Macrophages / enzymology
  • Mice
  • NF-kappa B / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • RAW 264.7 Cells

Substances

  • Anti-Inflammatory Agents
  • Cyclooxygenase 2 Inhibitors
  • Cytokines
  • Enzyme Inhibitors
  • Isocoumarins
  • Lipopolysaccharides
  • NF-kappa B
  • agrimonolide
  • Nitric Oxide Synthase Type II