Pharmacological characterization of the pseudopterosins:: Novel anti-inflammatory natural products isolated from the Caribbean soft coral, Pseudopterogorgia elisabethae

Pseudopterosin E (PSE), a C-10 linked fucose glycoside and pseudopterosin A (PSA), a C-9 xylose glycoside isolated from the marine gorgonian Pseudopterogorgia elisabethae were both effective in reducing PMA-induced 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-benzoquinone-induced writhing (ED50 (mg/kg, i.p.) PSE(14), PSA(4). PSE inhibited zymosan-induced writhing (ED50 = 6 mg/kg, i.p.), with a concomitant dose-dependent inhibition of peritoneal exudate 6-keto-prostaglandin F-1 alpha (ED50 = 24 mg/kg) and leukotriene C-4 (ED50 = 24 mg/kg). In vitro, the pseudopterosins were inactive as inhibitors of phospholipase A(2), cyclooxygenase, cytokine release, or as regulators of adhesion molecule expression. PSA inhibited prostaglandin E-2 and leukotriene C-4 production in zymosan-stimulated murine peritoneal macrophages (IC50 = 4 mu M and 1 mu M, respectively); however, PSE was much less effective. These data suggest that the pseudopterosins may mediate their antiinflammatory effects by inhibiting eicosanoid release from inflammatory cells in a concentration and dose-dependent manner. (C) 1998 Elsevier Science Inc.