Abstract
The aim of this study was to investigate the effect of naringenin (5,7,4'-trihydroxyflavanone), a citrus flavonoid, on dendritic cell (DC) maturation, as well as its potential as a therapeutic agent in a murine model of collagen-induced arthritis (CIA). Naringenin effectively inhibited lipopolysaccharide (LPS)-induced DC maturation as shown by reductions in the production of proinflammatory cytokines/chemokines, the expression of costimulatory molecules and the Ag-specific T cell priming ability of DCs when given at noncytotoxic doses. In addition, the decrease of LPS-induced MAPK and NF-κB signaling activation may contribute to the inhibitory activity of naringenin. In mice with CIA, the oral administration of naringenin ameliorated the severity of arthritis, reduced the levels of anticollagen Type II (CII) IgG and limited the proliferation of T cells, observed as a lower frequency of Th1 and Th17 cells in the spleen after restimulation with CII. In conclusion, this study shows for the first time that naringenin can manipulate the immunostimulatory properties of DCs and thus represents a potential therapeutic for the treatment of rheumatoid arthritis in humans.