The
diterpene,
12-acetoxyhawtriwaic acid lactone (AHAL,
tanabalin) isolated from the flower buds of Egletes viscosa Less. (Asteraceae) was evaluated on
capsaicin-induced ear
edema and hindpaw nociception in mice. AHAL (12.5, 25 and 50 mg/kg, P. O.) significantly attenuated the ear
edema response to topically applied
capsaicin (250 microg), in a dose-related manner. At similar doses, AHAL also suppressed the nocifensive paw-licking behavior induced by intraplantar injection of
capsaicin (1.6 microg). These responses to
capsaicin were also greatly inhibited by
ruthenium red (3 mg/kg, S. C.), a non-competitive
capsaicin receptor (TRPV1) antagonist. The anti-
edema effect of AHAL (50 mg/kg) seems unrelated to either blockade of mast cell degranulation or to
histamine and
serotonin receptor antagonism since AHAL did not modify the paw
edema response induced by intraplantar
injections of
compound 48/80,
histamine or
serotonin. However, the hindpaw
edema induced by
substance P and vascular permeability increase induced by intraperitoneal
acetic acid were significantly suppressed by AHAL. The antinociceptive effect of AHAL (50 mg/kg) was unaffected by
naloxone pretreatment but was significantly antagonized by
theophylline and
glibenclamide, the respective blockers of
adenosine and K(
ATP)-channels. AHAL (50 mg/kg, P. O.) did not impair the ambulation or motor coordination of mice in open-field and rota-rod tests. These data suggest that AHAL inhibits acute
neurogenic inflammation possibly involving
capsaicin-sensitive TRPV1-receptors, endogenous
adenosine and
ATP-sensitive potassium channels.