Inhibitory effects of nardostachin on nitric oxide, prostaglandin E 2, and tumor necrosis factor-α production in lipopolysaccharide activated macrophages

Abstract

Nardostachin, which is an iridoid isolated from Patrinia saniculaefolia, was examined by assessing its effect on the production of tumor necrosis factor-α (TNF-α) and expression of 2 enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in lipopolysaccharide (LPS)-stimulated Raw264.7 macrophages. This compound consistently inhibited the production of nitric oxide (NO) and TNF-α production in a dose-dependent manner, with respective IC50 values of 12.3 and 16.2 μM. The decrease in quantity of NO products was accompanied by a decrease in the iNOS protein level, as assessed by Western blotting probed with specific anti-iNOS antibodies. In addition, this compound also reduced the COX-2 protein expression level and the attendant PGE2 production in LPS-stimulated macrophages. These results suggest that nardostachin may be useful for inhibiting the production of inflammatory mediators such as TNF-α, NO and PGE2 in inflammatory diseases. © 2003 Pharmaceutical Society of Japan.