thiazolidinedione derivative suppresses lps-induced cox-2 expression and no production in raw 264.7 macrophages

The present study was designed to investigate the inhibitory effect of 2,4 bis[(4ethoxyphenyl)azo] 5(3hydroxybenzylidene) thiazolidine 2,4dione (tzdoch_2ch_3) on the cyclooxygenase2 (cox2) and inducible nitric oxide synthase (inos) in raw 264.7 cells. the effects of tzdoch_2ch_3 on cox2 and inos mrna expression in lps-activated raw 264.7 cells were detected by real time pcr. also, to understand structure and substrate specificity, we have utilized molecular docking simulations (auto dock vina) and the active residues in the binding pocket were determined from cox2 and inos. the treatment of raw 264.7 cells with tzdoch_2ch_3 significantly inhibited lps-induced cox2 mrna expression, corresponding to 46.1% and 61.06% at 30 and 60 μg/ml, respectively. the present study revealed that the tzdoch_2ch_3 had a little effect on inos mrna expression. meanwhile, the tzdoch_2ch_3 also could inhibit the production of no compared to single lps-stimulated cell. according to the results obtained, tzdoch_2ch_3 dramatically suppressed lipopolysaccharide (lps) induced nitric oxide (no) production after 24 h, in a concentration-dependent manner with an ic50 of 65 μg/ml. our data suggest that tzdoch_2ch_3, as a functionally novel agent, inhibits the inflammatory pathway via suppression of cox2 mrna expression and also by the inhibition of the inos activity. therefore, this compound could be suggested as a novel therapeutic strategy for inflammation associated disorders.