Attenuation of inflammatory responses by (+)-syringaresinol via MAP-Kinase-mediated suppression of NF-kappa B signaling in vitro and in vivo

Abstract

We examined the anti-inflammatory effects of (+)-syringaresinol (SGRS), a lignan isolated from Rubia philippinensis, in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells using enzyme-based immuno assay, Western blotting, and RT-PCR analyses. Additionally, in vivo effects of SGRS in the acute inflammatory state were examined by using the carrageenan-induced hind paw edema assay in experimental mice. As a result, treatment with SGRS (25, 50, and 100 mu M) inhibited protein expression of lipopolysaccharide-stimulated inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear factor kappa B (NF-kappa B) as well as production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1 beta), and interleukin-6 (IL-6) induced by LPS. Moreover, SGRS also reduced LPS-induced mRNA expression levels of iNOS and COX-2, including NO, PGE2, TNF-alpha, IL-1 beta, and IL-6 cytokines in a dose-dependent fashion. Furthermore, carrageenan-induced paw edema assay validated the in vivo anti-edema effect of SGRS. Interestingly, SGRS (30 mg/kg) suppressed carrageenan-induced elevation of iNOS, COX-2, TNF-alpha, IL-1 beta, and IL-6 mRNA levels as well as COX-2 and NF-kappa B protein levels, suggesting SGRS may possess anti-inflammatory activities.