Inhibition by hydroxyachillin, sesquiterpene lactone from Tanacetum microphyllum, of PMA-induced mouse ear oedema.
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.
Silván
A M
AM
Department of Pharmacology, Faculty of Pharmacy, University Complutense, Madrid, Spain.
Abad
M J
MJ
Bermejo
P
P
Villar
A
A
D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016718:Arachidonic Acid / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004423:Ear / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D015777:Eicosanoids / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D007783:Lactones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007928:Lethal Dose 50; D051379:Mice; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011493:Protein Kinase C / Q000378:metabolism*; D012015:Reference Standards; D012044:Regression Analysis; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013755:Tetradecanoylphorbol Acetate / Q000008:administration & dosage / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002273:Carcinogens; D015777:Eicosanoids; D007783:Lactones; D012717:Sesquiterpenes; C089156:hydroxyachillin; D016718:Arachidonic Acid; D011493:Protein Kinase C; D010741:Phospholipases A; D054467:Phospholipases A2; D013755:Tetradecanoylphorbol Acetate