title: Topically applied diterpenoids from Egletes viscosa (Asteraceae) attenuate the dermal inflammation in mouse ear induced by tetradecanoylphorbol 13-acetate- and oxazolone.
abstract: 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.
authors.affiliation: Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, Ceara, Brazil.
authors.forename: Iana Bantim Felício
authors.initials: IB
authors.lastname: Calou
authors.forename: Daniel Italo Maia
authors.initials: DI
authors.lastname: Sousa
authors.forename: Geanne Matos de Andrade
authors.initials: GM
authors.lastname: Cunha
authors.forename: Gerly Anne de Castro
authors.initials: GA
authors.lastname: Brito
authors.forename: Edilberto Rocha
authors.initials: ER
authors.lastname: Silveira
authors.forename: Vietla Satyanarayana
authors.initials: VS
authors.lastname: Rao
authors.forename: Flávia Almeida
authors.initials: FA
authors.lastname: Santos
mesh_terms: 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
chemical_list: 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