Vol. 304, Issue 3, 1172-1180, March 2003

Modulatory Effect of Bolinaquinone, a Marine Sesquiterpenoid, on Acute and Chronic Inflammatory Processes

Rut Lucas, Clelia Giannini, Maria Valeria D'auria and Miguel Payá

Departamento de Farmacología (R.L., M.P.), Universidad de Valencia, Facultad de Farmacia, Valencia, Spain; and Dipartimento di Chimica delle Sostanze Naturali (C.G., M.V.D.), Università degli Studi di Napoli, Naples, Italy

The marine metabolite bolinaquinone is a novel inhibitor of secretory phospholipase A₂ (sPLA₂), with a potency on the human synovial enzyme (group II) higher than that of manoalide. This activity on the sPLA₂ 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 B₄ (LTB₄) in calcimycin (A23187)-stimulated human neutrophils as a consequence of the inhibition of 5-lipoxygenase activity, as well as PGE₂ 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 ID₅₀ values of 76.7 µg/ear and 5.6 mg/kg, respectively, with a significant decrease in PGE₂, LTB₄, and tumor necrosis factor- (TNF-) 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 PGE₂, NO, and TNF- production in paw homogenates without affecting PGE₂ 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.