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Inhibition by hydroxyachillin, sesquiterpene lactone from Tanacetum microphyllum, of PMA-induced mouse ear oedema.

Abstract
4-beta-phorbol 12-myristate 13-acetate (PMA), when administered topically to mouse ear, induces a pronounced inflammatory response mediated by protein kinase C (PKC). Activation of PKC is implicated in the pathogenesis of inflammation, with phospholipase A2-dependent arachidonic acid release and eicosanoid production. We have investigated the effects of hydroxyachillin, a sesquiterpene lactone from Tanacetum microphyllum DC., on mouse ear oedema induced by PMA. The effects of this compound on swelling and other inflammatory parameters are described. Hydroxyachillin significantly (p < or = 0.01) inhibited ear swelling in a dose-dependent manner, and was as effective as the reference drugs. The PMA-induced vascular permeability was significantly (p < or = 0.05) reduced by hydroxyachillin at the highest dose (3 mg/ear). Histologically, the signs of inflammation were greatly reduced in the hydroxyachillin-treated ear lesions. These data suggest that hydroxyachillin is an effective anti-inflammatory agent in this model, and that the inhibition of PKC may be one of the mechanisms of hydroxyachillin's effect.
AuthorsA M Silván, M J Abad, P Bermejo, A Villar
JournalInflammation research : official journal of the European Histamine Research Society ... [et al.] (Inflamm Res) Vol. 45 Issue 6 Pg. 289-92 (Jun 1996) ISSN: 1023-3830 [Print] Switzerland
PMID8814460 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Carcinogens
  • Eicosanoids
  • Lactones
  • Sesquiterpenes
  • hydroxyachillin
  • Arachidonic Acid
  • Protein Kinase C
  • Phospholipases A
  • Phospholipases A2
  • Tetradecanoylphorbol Acetate
Topics
  • Administration, Topical
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, pharmacology, therapeutic use)
  • Arachidonic Acid (metabolism)
  • Capillary Permeability (drug effects)
  • Carcinogens (administration & dosage, toxicity)
  • Dose-Response Relationship, Drug
  • Ear (pathology)
  • Edema (chemically induced, drug therapy)
  • Eicosanoids (metabolism)
  • Enzyme Activation (drug effects)
  • Female
  • Lactones (administration & dosage, pharmacology, therapeutic use)
  • Lethal Dose 50
  • Mice
  • Phospholipases A (metabolism)
  • Phospholipases A2
  • Protein Kinase C (metabolism)
  • Reference Standards
  • Regression Analysis
  • Sesquiterpenes (administration & dosage, pharmacology, therapeutic use)
  • Tetradecanoylphorbol Acetate (administration & dosage, toxicity)

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