Cavernolide: a new inhibitor of human sPLA2 sharing unusual chemical features

• Published in: Life sciences (1973) Vol. 67; no. 24; pp. 3007 - 3014
• Main Authors: Posadas, I, Terencio, M C, De Rosa, S, Payá, M
• Format: Journal Article
• Language: English
• Published: Netherlands 03.11.2000
• Subjects: Animals; Blotting, Western; Cell Degranulation - drug effects; Cells, Cultured; Cyclooxygenase 2; Dinoprostone - metabolism; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Humans; Isoenzymes - biosynthesis; Macrophage Activation - drug effects; Macrophages - drug effects; Macrophages - enzymology; Membrane Proteins; Mice; Neutrophils - cytology; Neutrophils - drug effects; Neutrophils - enzymology; Nitric Oxide - metabolism; Nitric Oxide Synthase - biosynthesis; Nitric Oxide Synthase Type II; Peroxidase - metabolism; Phospholipases A - antagonists & inhibitors; Phospholipases A - metabolism; Phospholipases A2; Prostaglandin-Endoperoxide Synthases - biosynthesis; Synovial Membrane - enzymology; Terpenes - pharmacology; Tumor Necrosis Factor-alpha - metabolism; Zymosan - pharmacology
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/S0024-3205(00)00875-4

The inhibitory effect of cavernolide, a novel C2, terpene lactone isolated from the sponge Fasciospongia cavernosa, on PLA2 and other enzyme activities involved in the inflammatory process was studied. Cavernolide inhibited human synovial sPLA2 in a concentration-dependent manner with an IC50 value of 8.8 microM. Besides, this compound decreased in the nanomolar range the myeloperoxidase degranulation process using different stimuli. Cavernolide also inhibited TNFalpha, NO and PGE2 production in intact cell experiments. NO and PGE2 reduction was the consequence of the inhibition on iNOS and COX-2 expression because it did not affect inducible nitric oxide synthase and cyclooxygenase-2 activities in intact cells.