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.