The inhibitory effect of saPLIγ, a snake sourced PLA2 inhibitor on carrageenan-induced inflammation in mice

SaPLI gamma is a natural phospholipase A(2) (PLA(2)) inhibitor, isolated from Sinonatrix annularis, that has been demonstrated to protect against envenomation by other venomous snakes. As snake venom PLA(2)s and mammalian secretory PLA(2)s are similar, saPLI gamma is thought to have potential to alleviate inflammatory reactions in which PLA(2)s act as a key enzyme for arachidonic acid release. The aim of this study was to investigate the anti-inflammatory effects and mechanisms of action of saPLI gamma in an animal model of carrageenan-induced acute inflammation. The results indicated that saPLI gamma inhibited PLA(2) subtypes extensively, especially IIA-PLA(2), in a dose-dependent manner. Paw swelling in mice was reduced markedly by intraperitoneal saPLI gamma 2.5 mg/kg, and the effect was significantly better than observed with dexamethasone at the same dose. Lower neutrophil infiltration and tissue edema was observed in the paws of saPLI gamma-treated mice. Additionally, carrageenan-induced cyclooxygenase-2 (COX-2) and pro-inflammatory cytokines (TNF alpha and IL-1 beta) were also significantly downregulated by saPLI gamma in a dose-dependent manner. These results suggested that saPLI gamma had effective anti-inflammatory effects in vivo, and these were produced by blocking mammalian IB, IIA, V and X sPLA2 subtypes.