Luteolin Inhibits Microglia and Alters Hippocampal-Dependent Spatial Working Memory in Aged Mice

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A plant compound found in carrots, peppers, celery, olive oil, peppermint,

rosemary, chamomile etc. helps reduce age-related inflammation in the brain and

memory deficits, according to a new study conducted in mice.

J. Nutr. First published August 4, 2010; doi:10.3945/jn.110.123273

Journal of Nutrition, doi:10.3945/jn.110.123273

Vol. 140, No. 10, 1892-1898, October 2010

© 2010 American Society for Nutrition

Ingestive Behavior and Neurosciences

Luteolin Inhibits Microglia and Alters Hippocampal-Dependent Spatial Working

Memory in Aged Mice1,2,3

Saebyeol Jang4,5, N. Dilger5,6 and Rodney W. 4–6*

4 Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801; 5

Integrative Immunology and Behavior Program, University of Illinois, Urbana, IL

61801; 6 Department of Animal Sciences, University of Illinois, Urbana, IL 61801

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.

* To whom correspondence should be addressed. E-mail: rwjohn@....

Manuscript received February 26, 2010. Initial review completed March 26, 2010.

Revision accepted July 6, 2010.

Published online August 4, 2010.