Fluridone is a
herbicide extensively utilized in agriculture for its documented safety in animals.
Fluridone contains a 4(1H)-pyridone and a trifluoromethyl-
benzene moiety, which are also present in molecules with
analgesic and anti-inflammatory properties. The established absence of adverse effects of
Fluridone on animals prompted us to investigate whether it could represent a new anti-inflammatory compound targeting human cells. In stimulated human monocytes, micromolar
Fluridone inhibited
cyclooxygenase-2 expression and the release of
monocyte chemoattractant protein-1 and prostaglandin-E2, to a similar extent as
Acetylsalicylic acid.
Fluridone also inhibited the proliferation of aortic smooth muscle cells and reduced proliferation and
cytokine release by human activated lymphocytes. The mechanism of
Fluridone seems to rely on the dose-dependent inhibition of the nuclear translocation of nuclear factor-κB, a
transcription factor playing a pivotal role in
inflammation.
Fluridone also inhibited the release from stimulated human monocytes of
abscisic acid, a plant stress
hormone recently discovered also in mammalian cells, where it stimulates pro-inflammatory responses. Interestingly, the mechanism of
Fluridone's toxicity in plants relies on the inhibition of the
enzyme phytoene desaturase, involved in the biosynthetic pathway of ß-
carotene, the precursor of absciscic
acid in plants. Finally, administration of
Fluridone reduced peritoneal
inflammation in
Zymosan-treated mice. These results suggest that
Fluridone could represent a new prototype of anti-inflammatory
drug, also active on
abscisic acid pro-inflammatory pathway.