Abstract
Excessive production of proinflammatory mediators by activated brain microglia plays an important role in sickness behavior and neurodegenerative disorders. Luteolin, a flavonoid found in high concentrations in celery, green pepper, and perilla leaf and seeds, has been shown to reduce proinflammatory molecules produced by lipopolysaccharide (LPS)‐stimulated macrophages and microglia. In the present study, the anti‐inflammatory and subsequent neuroprotective effects of luteolin were investigated. Pretreatment of primary microglia and BV2 murine microglial cells with luteolin inhibited LPS‐stimulated production of proinflammatory cytokines such as TNF‐α and IL‐1β at both the gene and protein levels. Luteolin also suppressed LPS‐induced nitric oxide release in BV2 cells by regulating the expression of inducible nitric oxide synthase. In addition, the release of prostaglandin E2 and cyclooxygenase‐2 mRNA expression were inhibited by luteolin. In addition, treating Neuro‐2a cells with conditioned media from LPS‐stimulated microglia resulted in neuronal cell death. However, treating microglia with luteolin prior to LPS reduced neuronal cell death in a dose‐dependent manner. These results suggest that luteolin may be a useful agent counteracting neurotoxicity associated with activated microglia. This work was supported by NIH grants AG16710 and MH069148.Grant Funding SourceNIH
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