norathyriol and Pleurisy

A23187-induced pleurisy in the mouse was demonstrated in this study. The protein leakage, leukocyte accumulation, LTB4 and PGE2 production in the pleural cavity of mice were increased by A23187 in a dose-dependent manner. At 7.5 nmole A23187 intrapleural injection, the protein level peaked at 0.5-2 h, PMN leukocytes accumulation peaked at 3-4 h, and LTB4 and PGE2 production peaked at 0.5-1 h. In this in vivo model we investigated the anti-inflammatory effect of norathyriol, isolated from Tripterospermum lanceolatum. A23187-induced protein leakage was reduced by norathyriol (ID50 was about 30.6 mg/kg i.p.), indomethacin and BW755C. A23187-induced PMN leukocytes accumulation was suppressed by norathyriol (ID50 was about 16.8 mg/kg, i.p.) and BW755C, while enhanced by indomethacin. Like BW755C, norathyriol reduced both LTB4 and PGE2 production (ID50 was about 18.6 and 29.1 mg/kg i.p., respectively), while indomethacin reduced PGE2 but not LTB4 generation. We also demonstrated the analgesic effect of norathyriol on the acetic acid-induced writhing response. Acetic acid-induced writhing response was depressed by norathyriol (ID50 was about 27.9 mg/kg i.p.), indomethacin and ibuprofen. These results suggest that norathyriol, like BW755C, might be a dual, yet weak, cyclooxygenase and lipoxygenase pathway blocker. The inhibitory effect of norathyriol on the A23187-induced pleurisy and acetic acid-induced writhing response in mice is proposed to be dependent on the reduction of eicosanoids mediators formation in the inflammatory site.

Topics: 4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; Analgesia; Animals; Calcimycin; Dinoprostone; Female; Indomethacin; Kinetics; Leukocyte Count; Leukotriene B4; Mice; Neutrophils; Pleurisy; Radioimmunoassay; Xanthenes