Lycopene Inhibits Cyclooxygenase‐2 And Inflammatory Mediator Expression In Microglia

Microglia is the main immune defense in the central nervous system. Activation of microglia leads to production excessive inflammatory molecules and deleterious consequences for neuronal death. Lycopene, one of the major carotenoids present in tomatoes, shown to exert antioxidant properties and inhibition of cancer cell proliferation. However, the effect of lycopene on neuroinflammatory responses in microglia still remains unknown. In this study, we investigated the signaling pathways involves in lycopene‐inhibited cyclooxygenase‐2 (COX‐2) and inflammatory mediator expression in microglia cells. Here, we demonstrate that lycopene inhibites lipopolysaccharide (LPS)‐induced COX‐2 and inflammatory mediator expression through heme oxygenase‐1 (HO‐1) activation. Our data also demonstrates that stimulation of lycopene increases the phosphorylation of serine–threonine liver kinase B1( LKB1), Calcium/calmodulin‐dependent kinase II( CaMKII) and AMP‐activated protein kinase (AMPK) in microglia. Interestingly, we also found that activation of phosphorylation‐AMPK by lycopene accumulates in the nucleus in microglia. Moreover, pre‐incubated cells with HO‐1 or AMPK pharmacological inhibitors effectively reversed the inhibitory effect of lycopene on LPS‐induced COX‐2 expression. Furthermore, transfection cells with HO‐1 or AMPK siRNA significantly attenuated the inhibitory effect of lycopene as well. These findings suggest that lycopeneinhibites LPS‐induced COX‐2 expression is mediated by HO‐1 activation through the AMPK pathways. Our results also indicate that lycopene is a promising nature product and may be as a useful pharmacological agent for the treatment of neuroinflammation‐associated disorders.