Abstract

The aim of the present study was to evaluate the anti-inflammatory effect of four dimethoxy flavone derivatives; 7,2'-dimethoxy flavone, 7,3'-dimethoxy flavone, 7,4'-dimethoxy flavone and 7,8,-dimethoxy flavone and to investigate the possible cellular mechanisms involved. The acute anti-inflammatory effect of dimethoxy flavones was investigated by carrageenan induced hind paw oedema in rats. Further, the effect of dimethoxy flavones on certain mediators of pain and inflammation like cyclooxygenases (COX-1 and COX-2), pro-inflammatory cytokines (IL-1β and TNF-α) and free radical scavenging activity (NO and LPO) were investigated by using in vitro tests. The investigated dimethoxy flavones produced a significant, dose and time dependent reduction of carrageenan induced paw oedema in rats with a maximum inhibition of 52.4% observed for 7,4'-dimethoxy flavone. Although, the test compounds inhibited both the isoforms of cyclooxygenase, a higher degree of inhibition on COX-2 was evident. A concentration dependent inhibition of other inflammatory cytokines like tumor necrosis factor-α and interleukin-1β was identified in the present study. 7,4'-dimethoxy flavone was found to be maximally effective in inhibiting nitrite ion free radical generation and 7,8-dimethoxy flavone was more active in inhibiting lipid peroxidation than the other compounds. The results of the present study reveal the anti-inflammatory action of the investigated dimethoxy flavones. Inhibition of cyclooxygenases, cytokines and reactive oxygen species, observed in subsequent experiments may be suggested as possible mechanisms involved in the action of these compounds.

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