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 (microg/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 F1alpha (ED50 = 24 mg/kg) and leukotriene C4 (ED50 = 24 mg/kg). In vitro, the pseudopterosins were inactive as inhibitors of phospholipase A2, cyclooxygenase, cytokine release, or as regulators of adhesion molecule expression. PSA inhibited prostaglandin E2 and leukotriene C4 production in zymosan-stimulated murine peritoneal macrophages (IC50 = 4 microM and 1 microM, respectively); however, PSE was much less effective. These data suggest that the pseudopterosins may mediate their anti-inflammatory effects by inhibiting eicosanoid release from inflammatory cells in a concentration and dose-dependent manner.
Mayer
A M
AM
Midwestern University, Department of Pharmacology, Downers Grove, IL 60515, USA. amayer@midwestern.edu
Jacobson
P B
PB
Fenical
W
W
Jacobs
R S
RS
Glaser
K B
KB
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D003063:Cnidaria / Q000737:chemistry*; D016207:Cytokines / Q000378:metabolism; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D015777:Eicosanoids / Q000378:metabolism; D006027:Glycosides / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004224:Diterpenes; D015777:Eicosanoids; D006027:Glycosides; C049922:pseudopterosins