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3,5,6,7,8,3',4'-heptamethoxyflavone, a citrus polymethoxylated flavone, attenuates inflammation in the mouse hippocampus.

Okuyama S, Miyoshi K, Tsumura Y, Amakura Y, Yoshimura M, Yoshida T, Nakajima M, Furukawa Y - Brain Sci (2015)

Bottom Line: Citrus polymethoxylated flavones (PMFs) have recently been shown to suppress inflammation in peripheral tissues.We demonstrated that subcutaneously injected HMF suppressed: (1) LPS-induced losses in body weight; (2) LPS-induced microglial activation in the hippocampus; and (3) LPS-induced interleukin-1β mRNA expression in the hippocampus.These results suggest that HMF has the ability to reduce neuroinflammation in the brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. sokuyama@cc.matsuyama-u.ac.jp.

ABSTRACT
Citrus polymethoxylated flavones (PMFs) have recently been shown to suppress inflammation in peripheral tissues. In the present study, we investigated the effects of 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF), one of the PMFs, on inflammation in the brain in vivo using mice injected intrahippocampally with lipopolysaccharide (LPS). We demonstrated that subcutaneously injected HMF suppressed: (1) LPS-induced losses in body weight; (2) LPS-induced microglial activation in the hippocampus; and (3) LPS-induced interleukin-1β mRNA expression in the hippocampus. These results suggest that HMF has the ability to reduce neuroinflammation in the brain.

No MeSH data available.


Related in: MedlinePlus

Effects of HMF on the expression of microglia (IBA1) in the mouse hippocampus. The location of the captured images and quantification are shown with squares in the figure. (A) Sagittal sections of the hippocampus two days after the LPS intrahippocampal injection stained with an anti-IBA1 antibody; CON, LPS, LPS + HMF100. The scale bar shows 50 µm; (B) Quantitative analysis using Image J software of the total areas (pixels) of IBA1-positive cells in the hippocampus. Values are the means ± SEM. Symbols are significantly different for the following conditions: CON vs. LPS, * p < 0.05; LPS vs. LPS + HMF100, #p < 0.05.
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brainsci-05-00118-f003: Effects of HMF on the expression of microglia (IBA1) in the mouse hippocampus. The location of the captured images and quantification are shown with squares in the figure. (A) Sagittal sections of the hippocampus two days after the LPS intrahippocampal injection stained with an anti-IBA1 antibody; CON, LPS, LPS + HMF100. The scale bar shows 50 µm; (B) Quantitative analysis using Image J software of the total areas (pixels) of IBA1-positive cells in the hippocampus. Values are the means ± SEM. Symbols are significantly different for the following conditions: CON vs. LPS, * p < 0.05; LPS vs. LPS + HMF100, #p < 0.05.

Mentions: We investigated the effects of HMF on LPS-induced microglial overactivation. Microglial cells were immunostained with the IBA1 antibody. In all experimental groups, IBA1 immunoreactivity was detected in the stratum radiatum and stratum lacunosum-moleculare of the hippocampus that is near the LPS injection site (Figure 3A). IBA1-positive cells with the inactivated form (ramified microglia) were observed in the CON group. The morphology of IBA1-positive microglia was changed to “ameboid microglia” (the activated form) by the treatment with LPS, and the total area of these cells significantly increased (Figure 3B; * p < 0.05); on the other hand, HMF (100 mg/kg/day) treatment significantly suppressed the LPS-induced activation of microglia (Figure 3B; #p < 0.05).


3,5,6,7,8,3',4'-heptamethoxyflavone, a citrus polymethoxylated flavone, attenuates inflammation in the mouse hippocampus.

Okuyama S, Miyoshi K, Tsumura Y, Amakura Y, Yoshimura M, Yoshida T, Nakajima M, Furukawa Y - Brain Sci (2015)

Effects of HMF on the expression of microglia (IBA1) in the mouse hippocampus. The location of the captured images and quantification are shown with squares in the figure. (A) Sagittal sections of the hippocampus two days after the LPS intrahippocampal injection stained with an anti-IBA1 antibody; CON, LPS, LPS + HMF100. The scale bar shows 50 µm; (B) Quantitative analysis using Image J software of the total areas (pixels) of IBA1-positive cells in the hippocampus. Values are the means ± SEM. Symbols are significantly different for the following conditions: CON vs. LPS, * p < 0.05; LPS vs. LPS + HMF100, #p < 0.05.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493459&req=5

brainsci-05-00118-f003: Effects of HMF on the expression of microglia (IBA1) in the mouse hippocampus. The location of the captured images and quantification are shown with squares in the figure. (A) Sagittal sections of the hippocampus two days after the LPS intrahippocampal injection stained with an anti-IBA1 antibody; CON, LPS, LPS + HMF100. The scale bar shows 50 µm; (B) Quantitative analysis using Image J software of the total areas (pixels) of IBA1-positive cells in the hippocampus. Values are the means ± SEM. Symbols are significantly different for the following conditions: CON vs. LPS, * p < 0.05; LPS vs. LPS + HMF100, #p < 0.05.
Mentions: We investigated the effects of HMF on LPS-induced microglial overactivation. Microglial cells were immunostained with the IBA1 antibody. In all experimental groups, IBA1 immunoreactivity was detected in the stratum radiatum and stratum lacunosum-moleculare of the hippocampus that is near the LPS injection site (Figure 3A). IBA1-positive cells with the inactivated form (ramified microglia) were observed in the CON group. The morphology of IBA1-positive microglia was changed to “ameboid microglia” (the activated form) by the treatment with LPS, and the total area of these cells significantly increased (Figure 3B; * p < 0.05); on the other hand, HMF (100 mg/kg/day) treatment significantly suppressed the LPS-induced activation of microglia (Figure 3B; #p < 0.05).

Bottom Line: Citrus polymethoxylated flavones (PMFs) have recently been shown to suppress inflammation in peripheral tissues.We demonstrated that subcutaneously injected HMF suppressed: (1) LPS-induced losses in body weight; (2) LPS-induced microglial activation in the hippocampus; and (3) LPS-induced interleukin-1β mRNA expression in the hippocampus.These results suggest that HMF has the ability to reduce neuroinflammation in the brain.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan. sokuyama@cc.matsuyama-u.ac.jp.

ABSTRACT
Citrus polymethoxylated flavones (PMFs) have recently been shown to suppress inflammation in peripheral tissues. In the present study, we investigated the effects of 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF), one of the PMFs, on inflammation in the brain in vivo using mice injected intrahippocampally with lipopolysaccharide (LPS). We demonstrated that subcutaneously injected HMF suppressed: (1) LPS-induced losses in body weight; (2) LPS-induced microglial activation in the hippocampus; and (3) LPS-induced interleukin-1β mRNA expression in the hippocampus. These results suggest that HMF has the ability to reduce neuroinflammation in the brain.

No MeSH data available.


Related in: MedlinePlus