Sakuranetin Inhibits Inflammatory Enzyme, Cytokine, and Costimulatory Molecule Expression in Macrophages through Modulation of JNK, p38, and STAT1

Abstract

Sakuranetin is flavonoid phytoalexin that serves as a plant antibiotic and exists in Prunus and several other plant species. Recently, we identified the anti-inflammatory effect of Prunus yedoensis and found that there were few studies on the potential anti-inflammatory activity of sakuranetin, one of the main constituents of Prunus yedoensis. Here, we isolated peritoneal macrophages from thioglycollate-injected mice and examined whether sakuranetin affected the response of the macrophages in response to lipopolysaccharide (LPS) plus interferon- (IFN-) γ or LPS only. Sakuranetin suppressed the synthesis of iNOS and COX2 in LPS/IFN-γ stimulated cells and the secretion of TNF-α, IL-6, and IL-12 in LPS stimulated cells. The surface expression of the costimulatory molecules, CD86 and CD40, was also decreased. Among the LPS-induced signaling molecules, STAT1, JNK, and p38 phosphorylation was attenuated. These findings are evidence that sakuranetin acts as anti-inflammatory flavonoid and further study is required to evaluate its in vivo efficacy.