Anti-inflammatory Effects of Sinapic Acid through the Suppression of Inducible Nitric Oxide Synthase, Cyclooxygase-2, and Proinflammatory Cytokines Expressions via Nuclear Factor-κB Inactivation

To investigate the anti-inflammatory potential of sinapic acid as well as the underlying mechanism involved, we studied the inhibitory effect of sinapic acid on the production of pro-inflammatory mediators in vitro and then evaluated its in vivo anti-inflammatory effect. Sinapic acid inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E-2 (PGE(2)), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1 beta production in a dose-dependent manner. Consistent with these findings, sinapic acid inhibited LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygase (COX)-2 at the protein levels, and iNOS, COX-2, TNF-alpha, and IL-1 beta mRNA expression in RAW 264.7 macrophages, as determined by Western blotting and reverse-transcribed polymerase chain reaction, respectively. Sinapic acid suppressed the LPS-induced activation of nuclear factor-kappa B (NF-kappa B), a transcription factor pivotal necessary for pro-inflammatory mediators, such as iNOS, COX-2, TNF-alpha, and IL-1 beta. This effect was accompanied by a parallel reduction of the nuclear translocation of p65 and p50 NF-kappa B subunits, as well as I kappa B-alpha degradation and phosphorylation. The effects of sinapic acid on acute phase inflammation were investigated on serotonin- and carrageenan-induced paw edema and compared with indomethacin (10 mg/kg, p.o.) or ibuprofen (1100 mg/kg, p.o.). Maximum inhibitions of 34.2 and 44.5% were observed at a concentration of 30 mg/kg for serotonin- and carrageenan-induced paw edema, respectively. These results suggest that the suppressions of the expressions of iNOS, COX-2, TNF-alpha, and IL-1 beta via NF-kappa B inactivation are responsible for the anti-inflammatory effects of sinapic acid.