Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 31, Issue -, Pages 207-215Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2015.12.029
Keywords
Seseli gummiferum subsp corymbosum; Corymbocoumarin; NF-kappa B; Heme oxygenase-1; Inflammation; LPS
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Funding
- MRC grant from the National Research Foundation of Korea [2009-93146]
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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.
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