Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Aug;19(4):286-92.
doi: 10.1089/rej.2015.1708. Epub 2016 Feb 26.

Dietary Luteolin Reduces Proinflammatory Microglia in the Brain of Senescent Mice

Affiliations
Free PMC article

Dietary Luteolin Reduces Proinflammatory Microglia in the Brain of Senescent Mice

Michael D Burton et al. Rejuvenation Res. .
Free PMC article

Abstract

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.

Figures

<b>FIG. 1.</b>
FIG. 1.
Isolation of microglia from adult and aged mouse brain. Representative dot blots of isolated cells that were incubated with antibodies for extracellular markers CD11b and CD45 and analyzed by flow cytometry. Microglia were identified by CD11b+/CD45low staining. (a) Approximately 90%–95% of the viable cells isolated from adults were CD11b+/CD45low, (b) while 85%–90% of the viable cells isolated from aged mice were CD11b+/CD45low.
<b>FIG. 2.</b>
FIG. 2.
(a) Percentage of major histocompatibility complex (MHC) class II-positive microglia isolated from brains of adult and aged mice after 4-week consumption of control or luteolin-supplemented diet and (b) representative two-color dot blots from each condition. Values are mean ± SEM (n = 8–11). Labeled means without a common letter differ, p < 0.001.
<b>FIG. 3.</b>
FIG. 3.
(a) Percentage of interleukin (IL)-1β-positive microglia isolated from brains of adult and aged mice after 4-week consumption of control or luteolin-supplemented diet and (b) representative two-color dot blots from each condition. Values are mean ± SEM (n = 8–11). Labeled means without a common letter differ, p < 0.05.
<b>FIG. 4.</b>
FIG. 4.
(a) Percentage of IL-6-positive microglia isolated from brains of adult and aged mice after 4-week consumption of control or luteolin-supplemented diet and (b) representative two-color dot blots from each condition. Values are mean ± SEM (n = 8–11). Labeled means without a common letter differ, p < 0.05.
<b>FIG. 5.</b>
FIG. 5.
Percentage of MHC class II-positive (a), IL-1β-positive (b), and IL-6-positive (c) microglia isolated from brains of adult and aged mice after 4-week consumption of control or luteolin-supplemented diet and injection of lipopolysaccharide (LPS). Values are mean ± SEM (n = 8–11). Labeled means without a common letter differ, p < 0.04.
<b>FIG. 6.</b>
FIG. 6.
Food intake of adult and aged mice after 4-week consumption of control or luteolin-supplemented diet and injection of LPS. Food intake was measured for 4 hours after injection. Bars represent the mean ± SEM (n = 8–11). Labeled means without a common letter differ, p < 0.01.

Similar articles

See all similar articles

Cited by 10 articles

See all "Cited by" articles
Feedback