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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.
AuthorsIana Bantim Felício Calou, Daniel Italo Maia Sousa, Geanne Matos de Andrade Cunha, Gerly Anne de Castro Brito, Edilberto Rocha Silveira, Vietla Satyanarayana Rao, Flávia Almeida Santos
JournalBiological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 31 Issue 8 Pg. 1511-6 (Aug 2008) ISSN: 0918-6158 [Print] Japan
PMID18670081 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 12-acetoxyhawtriwaic acid lactone
  • Anti-Inflammatory Agents
  • Diterpenes
  • Fatty Acids, Unsaturated
  • Furans
  • Lactones
  • Tumor Necrosis Factor-alpha
  • centipedic acid
  • Oxazolone
  • Interferon-gamma
  • Peroxidase
  • Tetradecanoylphorbol Acetate
Topics
  • Acute Disease
  • Administration, Topical
  • Animals
  • Anti-Inflammatory Agents
  • Asteraceae (chemistry)
  • Chronic Disease
  • Dermatitis, Contact (drug therapy, pathology)
  • Diterpenes (administration & dosage, isolation & purification, pharmacology)
  • Ear, External (pathology)
  • Fatty Acids, Unsaturated (administration & dosage, isolation & purification, pharmacology)
  • Flowers (chemistry)
  • Furans (administration & dosage, isolation & purification, pharmacology)
  • Interferon-gamma (metabolism)
  • Lactones (administration & dosage, isolation & purification, pharmacology)
  • Male
  • Mice
  • Oxazolone
  • Peroxidase (metabolism)
  • Skin (pathology)
  • Tetradecanoylphorbol Acetate
  • Tumor Necrosis Factor-alpha (metabolism)

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