Saucerneol D inhibits eicosanoid generation and degranulation through suppression of Syk kinase in mast cells

Previously we reported that saucerneol D (SD), a naturally occurring sesquilignan isolated from Saururus chinensis (S. chinensis) suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 cells. The aim of this study was to elucidate whether SD modulates the generation of other inflammatory mediators in activated mast cells. We investigated the effects of SD on cyclooxygenase-2 (COX-2)-dependent prostaglandin D-2 (PCD2) and 5-lipoxygenase (5-LO)-dependent leukotriene C-4 (LTC4) generations as well as degranulation in cytokine-stimulated mouse bone marrow-derived mast cells (BMMCs). Biochemical analyses of the cytokine-mediated signaling pathways showed that SD suppressed the phosphorylation of Syk kinase and multiple downstream signaling processes including phospholipase C gamma 1 (PLC gamma 1)-mediated intracellular Ca2+ influx and activation of mitogen-activated protein kinases (MAPKs; including extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase UNK) and p38) and the nuclear factor-kappa B (NF-kappa B) pathway. Taken together, the present study suggests that SD suppresses eicosanoid generation and degranulation through Syk-dependent pathway in BMMCs. Crown Copyright (C) 2012 Published by Elsevier Ltd. All rights reserved.