Anti-inflammatory effect of sophoraflavanone G isolated from Sophora flavescens in lipopolysaccharide-stimulated mouse macrophages

Sophoraflavanone G (SG; 5,7,D, 2',4'-tetrahydroxy-8-lavandulylflavanone) has been isolated from Sophora flavescens and found to be effective against bacteria and to decrease cyclooxygenase (COX)-2 expression in RAW 264.7 macrophage. However, the anti-inflammatory mechanisms of SG are not well understood. RAW 264.7 cells were pretreated with various concentrations of SG (2.5-20 mu M) and inflammatory responses were induced with lipopolysaccharide. Using enzyme-linked immunosorbent assay, the levels of pro-inflammatory cytokines and prostaglandin E-2 (PGE(2)) were determined. Western blot was used to examine the protein expression of inducible nitric oxide synthase (iNOS), COX-2, and heme oxygenase-1 (HO-1). To investigate the molecular mechanism, we analyzed inflammatory-associated signaling pathways, including nuclear transcription factor kappa-B (NF-kappa B) and mitogen-activated protein kinase (MAPK). SG inhibited the levels of nitric oxide and PGE(2) and decreased the production of pro-inflammatory cytokines, such as interleukin (1)-1 beta, IL-6, and tumor necrosis factor alpha. The expression of iNOS and COX-2 was also suppressed. However, SG increased HO-1 production in a concentration-dependent manner and significantly decreased MAPK activation and inhibited NF-kappa B subunit p65 proteins to translocate into the nucleus. These results suggest that SG has an anti-inflammatory effect, inhibiting pro-inflammatory cytokines and mediators production via interruption of the NF-kappa B and MAPK signaling pathways. (C) 2013 Elsevier Ltd. All rights reserved.