Anti-inflammatory profile of dehydrocostic acid, a novel sesquiterpene acid with a pharmacophoric conjugated diene.
Sesquiterpene acids are natural products that, in contrast with the thoroughly studied sesquiterpene lactones, have received little pharmacological attention. A good source of this class of compounds is Inula viscosa (Asteraceae), a plant with documented anti-inflammatory effects. The present paper gives the results of our investigations on the biochemical mechanisms involved in the anti-inflammatory activity of one such compound, dehydrocostic acid. The most salient findings were that in vitro dehydrocostic acid inhibits leukotriene B(4) production (IC(50)=22 microM), elastase activity (IC(50)=43 microM) and bee venom phospholipase A(2) activity (IC(50)=17 microM). Furthermore, this sesquiterpenoid was effective on some models of acute edema induced by PLA(2) and 12-O-tetradecanoylphorbol 13-acetate (TPA) Comparison of these data with that known for ilicic acid firmly suggests that the presence of a semiplanar ring A is essential for an improved inhibitory activity on inflammatory mediators.
Hernández
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Departament de Farmacologia, Facultat de Farmàcia, Universitat de València, Av. Vicent Andrés Estellés s/n, 46100 Burjassot, Spain.
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Giner
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D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D003872:Dermatitis / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D020128:Inhibitory Concentration 50; D038143:Inula / Q000737:chemistry*; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D010741:Phospholipases A / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D035261:Plant Components, Aerial / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D012717:Sesquiterpenes; C509816:dehydrocostic acid; D007975:Leukotriene B4; D010741:Phospholipases A; D010196:Pancreatic Elastase; D013755:Tetradecanoylphorbol Acetate