A dysregulated overexpression of inflammatory mediators by microglia may facilitate cognitive aging and neurodegeneration. Considerable evidence suggests the
flavonoid luteolin has antiinflammatory effects, but its ability to inhibit microglia, reduce inflammatory mediators, and improve hippocampal-dependent learning and memory in aged mice is unknown. In initial studies, pretreatment of BV-2 microglia with
luteolin inhibited the induction of inflammatory genes and the release of inflammatory mediators after
lipopolysaccharide (LPS) stimulation. Supernatants from LPS-stimulated microglia caused discernible death in Neuro.2a cells. However, treating microglia with
luteolin prior to LPS reduced neuronal cell death caused by conditioned supernatants, indicating
luteolin was neuroprotective. In subsequent studies, adult (3-6 mo) and aged (22-24 mo) mice were fed control or
luteolin (20 mg/d)-supplemented diet for 4 wk and spatial working memory was assessed as were several inflammatory markers in the hippocampus. Aged mice fed control diet exhibited deficits in spatial working memory and expression of inflammatory markers in the hippocampus indicative of increased microglial cell activity.
Luteolin consumption improved spatial working memory and restored expression of inflammatory markers in the hippocampus compared with that of young adults.
Luteolin did not affect either spatial working memory or inflammatory markers in young adults. Taken together, the current findings suggest dietary
luteolin enhanced spatial working memory by mitigating microglial-associated
inflammation in the hippocampus. Therefore,
luteolin consumption may be beneficial in preventing or treating conditions involving increased microglial cell activity and
inflammation.