Luteolin and chrysin differentially inhibit cyclooxygenase-2 expression and scavenge reactive oxygen species but similarly inhibit prostaglandin-E ₂ formation in RAW 264.7 cells

Inflammation and oxidative stress are associated with cancer, atherosclerosis, and other chronic diseases. Dietary flavonoids have been reported to possess antiinflammatory and antioxidant properties, but their mechanisms of action and structure-activity relations have not been fully investigated. We hypothesized that differences in antioxidant activity between the structurally similar flavones, luteolin and chrysin (differing only in B-ring hydroxylation patterns), would differentially affect inflammation- associated Cox-2 expression and PGE₂ formation. Pretreatment of RAW 264.7 macrophage-like cells with 25, 50, or 100 μmol/L concentrations of luteolin inhibited lipopolysaccharide (LPS)-induced Cox-2 protein expression (P < 0.0001). Chrysin pretreatment did not reduce LPS-induced Cox-2 protein expression at any level tested. Conversely, both luteolin and chrysin completely suppressed LPS-induced PGE₂ formation (P < 0.001). Luteolin, but not chrysin, inhibited xanthine/xanthine oxidase-generated superoxide formation at 100 μmol/L in a cell-free system (P < 0.001). Although both luteolin and chrysin reduced LPS-induced hydroxyl radical formation relative to the positive control (P < 0.001), luteolin was superior to chrysin (P = 0.003). In summary, luteolin and chrysin suppressed PGE₂ formation equally well, despite differential effects on Cox-2 protein expression and on superoxide and hydroxyl radical scavenging. These data indicate that flavones may display similar antiinflammatory activity via different mechanisms.