PHARMACOLOGICAL CHARACTERIZATION OF THE PSEUDOPTEROSINS - NOVEL ANTIINFLAMMATORY NATURAL-PRODUCTS ISOLATED FROM THE CARIBBEAN SOFT CORAL, PSEUDOPTEROGORGIA-ELISABETHAE

Pseudopterosin E (PSE), a C-10 linked fucose glycoside and pseudoptero sin A (PSA), a C-9 xylose glycoside isolated from the marine gorgonian Pseudopterogorgia elisabethae were both effective in reducing PMA-ind uced mouse ear edema when administered topically (ED50 (mu g/ear) PSE( 38), PSA(8)) or systemically (ED50 (mg/kg, i.p.) PSE (14), PSA (32)). Both compounds exhibited in vivo analgesic activity in phenyl-p-benzoq uinone-induced writhing (ED50 (mg/kg, i.p.) PSE(14), PSA(4). PSE inhib ited zymosan-induced writhing (ED50 = 6 mg/kg, i.p.), with a concomita nt dose-dependent inhibition of peritoneal exudate 6-keto-prostaglandi n F-1 alpha (ED50 = 24 mg/kg) and leukotriene C-4 (ED50 = 24 mg/kg). I n vitro, the pseudopterosins were inactive as inhibitors of phospholip ase A(2), cyclooxygenase, cytokine release, or as regulators of adhesi on molecule expression. PSA inhibited prostaglandin E-2 and leukotrien e C-4 production in zymosan-stimulated murine peritoneal macrophages ( IC50 = 4 mu M and 1 mu M, respectively); however, PSE was much less ef fective. These data suggest that the pseudopterosins may mediate their antiinflammatory effects by inhibiting eicosanoid release from inflam matory cells in a concentration and dose-dependent manner. (C) 1998 El sevier Science Inc.