Modulation of the cyclooxygenase pathway via inhibition of nitric oxide production contributes to the anti-inflammatory activity of kaempferol

Kaempferol has been reported to inhibit nitric oxide synthase and cyclooxygenase enzymes in animal models. The present study was designed to investigate whether kaempferol modulates the cyclooxygenase pathway via inhibition of nitric oxide production, which in turn contributes to its anti-inflammatory activity. Investigations were performed using carrageenan induced rat air pouch model. Inflammation was assessed by measurement of nitrites (nitrite, a breakdown product of nitric oxide), prostaglandin-E-2 levels and cellular infiltration in the pouch fluid exudates. To assess the anti-inflammatory effect of the extract, rat air pouch linings were examined histologically. The levels of nitrite and prostaglandin-E-2 in pouch fluid were measured by using Griess assay and ELISA respectively. Cell counts and differential counts were performed using a Coulter counter and Wright-Giemsa stain respectively. Kaempferol when administered orally at 50 and 100 mg/kg dose showed significant inhibition of carrageenan induced production of nitrite (40.12 and 59.74%, respectively) and prostaglandin-E-2 generation (64.23 and 78.55%, respectively). Infiltration of the cells into the rat granuloma air pouch was also significantly inhibited by kaempferol. Modulation of cyclooxygenase pathway via inhibition of nitric oxide synthesis significantly contributes to kaempferol's anti-inflammatory activity. The present study characterizes the effects and mechanisms of naturally occurring phenolic flavonoid kaempferol, on inducible nitric oxide synthase expression and nitric oxide production. These results partially explain the pharmacological efficacy of flavonoids in general and kaempferol in particular as anti-inflammatory compounds. (C) 2010 Elsevier B.V. All rights reserved.