Saucerneol D, a naturally occurring sesquilignan, inhibits LPS-induced iNOS expression in RAW264.7 cells by blocking NF-κB and MAPK activation

We evaluated the ability of saucerneol D (SD), a tetrahydrofuran-type sesquilignan isolated from Saururus chinensis, to regulate the expression of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated murine macrophage-like RAW264.7 cells. SD consistently inhibited nitric oxide (NO) production in a dose-dependent manner, with an IC50 of 2.62 µM, and also blocked LPS-induced iNOS expression. SD potently suppressed both the reporter gene expression and DNA-binding activity of nuclear factor-κB (NF-κB). In addition, SD inhibited IκB-α degradation in a concentration- and time-dependent manner. SD also inhibited LPS-induced activation of various mitogen-activated protein kinases, including extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH2-terminal kinase (JNK). These findings suggest that SD may inhibit LPS-induced iNOS expression by blocking NF-κB and MAPK activation.