The marine metabolite
bolinaquinone is a novel inhibitor of secretory
phospholipase A(2) (
sPLA(2)), with a potency on the human synovial
enzyme (group II) higher than that of
manoalide. This activity on the
sPLA(2) was confirmed in vivo in the 8-h
zymosan rat air pouch on the secretory
enzyme accumulation in the pouch exudate. Additionally,
bolinaquinone decreased potently the synthesis and release of
leukotriene B(4) (LTB(4)) in
calcimycin (A23187)-stimulated human neutrophils as a consequence of the inhibition of
5-lipoxygenase activity, as well as
PGE(2) and NO production on
zymosan-stimulated mouse peritoneal macrophages. This compound exerted anti-inflammatory effects by topical and oral routes on the mouse ear
edema induced by 12-O-tetradecanoylphorbolacetate, with ID(50) values of 76.7 microg/ear and 5.6 mg/kg, respectively, with a significant decrease in
PGE(2), LTB(4), and
tumor necrosis factor-alpha (
TNF-alpha) levels being more effective than
indomethacin. This effect was confirmed in the mouse paw
carrageenan edema after
oral administration. Moreover,
bolinaquinone was able to reduce the inflammatory response of
adjuvant arthritis by inhibiting
PGE(2), NO, and
TNF-alpha production in paw homogenates without affecting
PGE(2) levels in the stomach. Additionally,
bolinaquinone inhibited
inducible nitric oxide synthase expression and reduced the degree of
bone resorption, soft tissue swelling, and
osteophyte formation.