1.
Cacospongionolide B is a novel marine metabolite isolated from the sponge Fasciospongia cavernosa. In in vitro studies, this compound inhibited
phospholipase A2 (PLA2), showing selectivity for secretory PLA2 (
sPLA2) versus cytosolic PLA2 (cPLA2), and its potency on the human synovial
enzyme (group II) was similar to that of
manoalide. 2. This activity was confirmed in vivo in the 8 h
zymosan-injected rat air pouch, on the secretory
enzyme accumulating in the pouch exudate.
Cacospongionolide B, that is bioavailable when is given orally, reduced the elevated levels of
sPLA2 present in paw homogenates of rats with
adjuvant arthritis. 3. This marine metabolite showed topical anti-inflammatory activity on the mouse ear oedema induced by 12-O-tetradecanoylphorbol
acetate (TPA) and decreased
carrageenin paw oedema in mice after
oral administration of 5, 10 or 20 mg kg(-1). 4. In the mouse air pouch injected with
zymosan,
cacospongionolide B administered into the pouch, induced a dose-dependent reduction in the levels of
eicosanoids and tumour
necrosis factor alpha (
TNFalpha) in the exudates 4 h after the stimulus. It also had a weak effect on cell migration. 5. The inflammatory response of
adjuvant arthritis was reduced by
cacospongionolide B, which did not significantly affect
eicosanoid levels in serum, paw or stomach homogenates and did not induce toxic effects. 6
Cacospongionolide B is a new inhibitor of
sPLA2 in vitro and in vivo, with anti-inflammatory properties in acute and chronic
inflammation. This marine metabolite was active after
oral administration and able to modify
TNFalpha levels, and may offer an interesting approach in the search for new
anti-inflammatory agents.