Effect of aristolochic acid on arachidonic acid cascade and in vivo models of inflammation.
Recently, it has been reported that aristolochic acid inhibits phospholipase A2 (PLA2) in vitro and also decrease either oedema induced by snake venom and human synovial fluid PLA2. The aim of this research was to study the antiinflammatory activity of aristolochic acid and to investigate the effect of the alkaloid on the enzymes involved in the release of eicosanoids. Our results demonstrate that aristolochic acid is able to inhibit inflammation induced by immunological, immune complexes, and nonimmunological agents such as carrageenan or croton oil. We suggest that one mechanism of the antiinflammatory activity of alkaloid may be by directly blocking PLA2 catalyzed release of arachidonic acid. Moreover, this study demonstrates that aristolochic acid could also inhibit other steps involved in eicosanoids release such as cyclooxygenase and lipooxygenase pathways.
Moreno
J J
JJ
Departamento de Ciencias Fisiológicas, Fac. Farmacia, Univ. Barcelona, Spain.
D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D034341:Aristolochic Acids; D001183:Arthus Reaction; D002351:Carrageenan / Q000633:toxicity; D003436:Croton Oil / Q000633:toxicity; D004195:Disease Models, Animal; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006967:Hypersensitivity / Q000188:drug therapy; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D010616:Phenanthrenes / Q000494:pharmacology* / Q000627:therapeutic use; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013931:Thromboxanes / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D034341:Aristolochic Acids; D010616:Phenanthrenes; D013931:Thromboxanes; D016718:Arachidonic Acid; D003436:Croton Oil; D002351:Carrageenan; C000228:aristolochic acid I; D010741:Phospholipases A; D054467:Phospholipases A2