Inhibition of nitric oxide synthesis in mouse macrophage cells by feverfew supercritical extract

Phytother Res. 2012 Apr;26(4):541-5. doi: 10.1002/ptr.3594. Epub 2011 Sep 16.


Feverfew is the most commonly used medicinal herb against migraine headache. The antimigraine mechanism of feverfew supercritical extract was investigated in vitro using the mouse macrophage cell line (RAW 264.7). Mouse macrophage cells were treated with lipopolysaccharide in the presence and absence of feverfew extracts. Inhibition of lipopolysaccharide-induced nitric oxide and TNF-α synthesis were quantified by ELISA. The mRNA and protein expression of iNOS and eNOS genes were analysed by RT-PCR and western blot analysis, respectively. The feverfew extract inhibited both nitric oxide (NO) and TNF-α production in a dose-dependent manner with complete inhibition of NO occurring at 5 µg/mL of feverfew extract. Both eNOS and iNOS mRNA levels were unchanged with the feverfew treatment. However, eNOS and iNOS proteins were significantly down-regulated by the feverfew extract. Feverfew inhibition of NO is due to the down-regulation of both eNOS and iNOS enzymes at the translational and/or post-translational level.

MeSH terms

  • Animals
  • Blotting, Western
  • Carbon Dioxide / metabolism
  • Cell Line
  • Cell Survival
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Lipopolysaccharides / adverse effects
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / metabolism
  • Nitric Oxide Synthase Type III / metabolism
  • Plant Extracts / pharmacology*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tanacetum parthenium / chemistry*
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism


  • Lipopolysaccharides
  • Plant Extracts
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Carbon Dioxide
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos2 protein, mouse
  • Nos3 protein, mouse