The
diterpene compounds,
centipedic acid (CA) and
12-acetoxyhawtriwaic acid lactone (AHAL,
tanabalin) isolated from the flower buds of Egletes viscosa LESS. (Asteraceae) were evaluated on acute and chronic models of mouse ear
dermatitis. A single topical application of CA (0.125; 0.25 and 0.5 mg/ear) or AHAL (0.125, 0.25, 0.5 mg/ear) immediately before 12-O-tetradecanoylphorbol-13-acetate (TPA, 2.5 mug/ear) caused a dose-related significant inhibition of ear inflammatory
edema and influx of polymorphonuclear cells, as evidenced by a decrease in ear thickness and reduced
myeloperoxidase (MPO) activity and
tumor necrosis factor-alpha (
TNF-alpha) in ear tissue homogenates. The maximal obtained inhibition for both ear
edema and neutrophil influx were almost similar to that of topically applied
dexamethasone (0.05 mg/ear). The extent of inhibitions for the respective treatments of CA (0.5 mg/ear), AHAL (0.5 mg/ear), or
dexamethasone (0.05 mg/ear) were in the order of 63%, 61% and 81% for the ear
edema, and 90%, 95% and 95% for the neutrophil influx. Also, at similar doses, both
diterpenes and
dexamethasone effectively inhibited the delayed-type
hypersensitivity reaction induced by repeated topical application of 1%
oxazolone (OXA, 20 microl/ear), as evidenced by significant decreases in ear thickness and
interferon-gamma (INF-gamma) levels in ear tissue. Histopathological analysis revealed a marked decrease in epidermal
hyperplasia and neutrophil infiltration in animals pretreated with CA or AHAL, in a manner similar to
dexamethasone. These data provide evidence for the anti-
dermatitis effect of Egletes viscosa
diterpenes, by mechanisms that involve a reduced neutrophil influx and decreased production of inflammatory
cytokines,
TNF-alpha and IFN-gamma.