Anti-inflammatory effect of corymbocoumarin from Seseli gummiferum subsp corymbosum through suppression of NF-κB signaling pathway and induction of HO-1 expression in LPS-stimulated RAW 264.7 cells

This study investigated the anti-inflammatory activity of corymbocoumarin, an angular-type pyranocoumarin isolated from Seseli gummiferum subsp. cotymbosum in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, Corymbocoumarin not only inhibited the production of nitric oxide (NO) and prostaglandin E-2 (PGE(2)), but also inhibited the protein and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Corymbocoumarin also attenuated pro-inflammatory cytokine tumor necrosis factor-alpha (TNT-alpha). Investigation of the effect on nuclear factor KB (NF-kappa B) signaling pathway showed that corymbocoumarin inhibited the phosphorylation of Akt and inhibitory kappa B (I kappa B)-alpha and decreased the subsequent translocation of the p65 and p50 NF-kappa B subunits to the nucleus. A further study revealed that corymbocoumarin exerted anti-inflammatory activity through induction of heme oxygenase (HO)-1 expression. The in vivo study showed that corymbocoumarin (20 mg/kg, i.p.) reduced paw swelling in carrageenan-induced acute inflammation model. Taken together, these results suggest that corymbocoumarin exerts its anti-inflammatory effect in LPS-stimulated RAW 264.7 cells by suppressing NF-kappa B activation and inducing HO-1 expression. Corymbocoumarin may provide a useful therapeutic approach for inflammation-associated diseases. (C) 2015 Elsevier B.V. All rights reserved.