Inhibition by licochalcone A, a novel flavonoid isolated from liquorice root, of IL-1β-induced PGE2 production in human skin fibroblasts

Abstract

Licochalcone A, a novel flavonoid isolated from the root of Glycyrrhiza inflata, has been reported to exhibit anti-inflammatory activity in animal models. In this study, we examined the effect of licochalcone A on the production of chemical mediators such as prostaglandin (PG)E2 and cytokines by interleukin (IL)-1β in human skin fibroblasts. Licochalcone A (IC50 15.0 nm) inhibited PGE2 production, but not IL-6 and IL-8 production, in response to IL-1β. NS-398 (IC50 1.6 nm), a COX-2 selective inhibitor, also suppressed the PGE2 production. Furthermore, licochalcone A and NS-398 suppressed PGF2α production by IL-1β. However, licochalcone A (1 μm) had no effect on increased levels of cyclooxygenase (COX)-2 mRNA and protein in cells. Dexamethasone (100 nm) not only inhibited PGE2, PGF2α, IL-6 and IL-8 production but also strongly suppressed the expression of COX-2 mRNA and protein. Licochalcone A had no effect on COX-1-dependent PGE2 production, whereas indometacin (100 nm), a dual inhibitor of COX-1 and COX-2, was very effective. These results suggest that licochalcone A induces an anti-inflammatory effect through the inhibition of COX-2-dependent PGE2 production. Furthermore, it appears that the inhibitory effect of licochalcone A on PGE2 production in response to IL-1β is quite different from that of the steroid.