Topically applied diterpenoids from Egletes viscosa (Asteraceae) attenuate the dermal inflammation in mouse ear induced by tetradecanoylphorbol 13-acetate- and oxazolone.
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.
Calou
Iana Bantim Felício
IB
Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceara, Brazil.
Sousa
Daniel Italo Maia
DI
Cunha
Geanne Matos de Andrade
GM
Brito
Gerly Anne de Castro
GA
Silveira
Edilberto Rocha
ER
Rao
Vietla Satyanarayana
VS
Santos
Flávia Almeida
FA
D000208:Acute Disease; D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents; D019659:Asteraceae / Q000737:chemistry*; D002908:Chronic Disease; D003877:Dermatitis, Contact / Q000188:drug therapy* / Q000473:pathology*; D004224:Diterpenes / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D004431:Ear, External / Q000473:pathology; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D035264:Flowers / Q000737:chemistry; D005663:Furans / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D007783:Lactones / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010081:Oxazolone; D009195:Peroxidase / Q000378:metabolism; D012867:Skin / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C513234:12-acetoxyhawtriwaic acid lactone; D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D005231:Fatty Acids, Unsaturated; D005663:Furans; D007783:Lactones; D014409:Tumor Necrosis Factor-alpha; C531023:centipedic acid; D010081:Oxazolone; D007371:Interferon-gamma; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate