Dietary Luteolin Reduces Proinflammatory Microglia in the Brain of Senescent Mice

Brain microglia become dysregulated during aging and express proinflammatory cytokines that play a role in cognitive aging. Recent studies suggest the flavonoid luteolin reduces neuroinflammation and improves learning and memory in aged mice. However, if dietary luteolin reduces microglia activity in the brain of senescent mice is not known. We hypothesized that feeding aged mice a diet with luteolin would reduce microglia activity. Adult (3-6 months) and aged (22-24 months) mice were fed American Institute of Nutrition (AIN)-93M or AIN-93M with luteolin (6 g/kg) for 4 weeks and injected intraperitoneally with saline or lipopolysaccharide (LPS) before microglia were isolated and stained for major histocompatibility complex (MHC) class II, interleukin (IL)-1β, and IL-6 for flow cytometry. In saline-treated mice fed control diet, aging increased the proportion of microglia that stained for MHC class II (<3% for adults vs. 23% for aged), IL-1β (<2% for adults vs. 25% for aged), and IL-6 (<2% for adults vs. 25% for aged), indicating an age-related increase in proinflammatory microglia. In saline-treated aged mice fed luteolin, the proportion of microglia that stained for MHC class II, IL-1β, and IL-6 was reduced by nearly half (to 12%, 13%, and 12%, respectively). Interestingly, luteolin significantly reduced the proportion of microglia that stained for IL-1β and IL-6 in LPS-treated adult mice but not aged. Collectively, the results show that a diet supplemented with luteolin inhibited brain microglia activity during aging and activation by LPS in adults. Therefore, luteolin may inhibit neuroinflammation and improve cognition in the otherwise healthy aged by constraining brain microglia.