Down‐regulatory effect of usnic acid on nuclear factor‐κB‐dependent tumor necrosis factor‐α and inducible nitric oxide synthase expression in lipopolysaccharide‐stimulated macrophages RAW 264.7

The purpose of this study was to investigate the molecular mechanisms that are responsible for the antiinflammatory effect of usnic acid (UA). UA is one of the most common and abundant lichen metabolites. The present study examined the effects of UA on the tumor necrosis factor‐α (TNF‐α) and nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 macrophages and the underlying molecular mechanisms. UA decreased the TNF‐α level in LPS‐stimulated RAW264.7 macrophages in dose‐dependent manner, the IC₅₀ value was 12.8 µM. RT‐PCR analysis indicated that it inhibited TNF‐α mRNA expression. Furthermore, it inhibited NO production in LPS‐activated RAW264.7 macrophages, the IC₅₀ value was 4.7 µM. Western blot analysis showed that UA attenuated LPS‐induced synthesis of iNOS protein and nuclear translocation of NF‐κB p65 in the macrophages, in parallel. UA also inhibited LPS‐mediated I‐κBα degradation. Taken together, this suggests that UA has an antiinflammatory effect by inhibiting TNF‐α and iNOS expression, possibly through suppression of nuclear translocation of NF‐κB p65 and I‐κBα degradation. Copyright © 2008 John Wiley & Sons, Ltd.