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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 mRNAs for inflammatory markers in the hippocampus. Hippocampal tissues were prepared two days after LPS intrahippocampal injection, and RT-PCR analysis was performed with specific primers. Densitometric quantification of mRNAs of COX-2 (A), IL-1β (B), TNF-α (C) and iNOS (D) band intensities normalized by the β-actin mRNA band in the hippocampus. Values are the means ± SEM. Symbols are significantly different for the following conditions: CON vs. LPS, *** p < 0.001; LPS vs. LPS + HMF100, #p < 0.05.
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brainsci-05-00118-f004: Effects of HMF on the expression of mRNAs for inflammatory markers in the hippocampus. Hippocampal tissues were prepared two days after LPS intrahippocampal injection, and RT-PCR analysis was performed with specific primers. Densitometric quantification of mRNAs of COX-2 (A), IL-1β (B), TNF-α (C) and iNOS (D) band intensities normalized by the β-actin mRNA band in the hippocampus. Values are the means ± SEM. Symbols are significantly different for the following conditions: CON vs. LPS, *** p < 0.001; LPS vs. LPS + HMF100, #p < 0.05.

Mentions: As activated microglia are known to contribute to neurodegenerative processes by producing various cytotoxic molecules, including proinflammatory cytokines [18,19,20], we examined the effects of HMF on the LPS-induced gene expression of proinflammatory cytokines (IL-1β and TNF-α) and enzyme (iNOS and COX-2) with RT-PCR. Figure 4B shows that IL-1β mRNA expression in the LPS group was significantly higher than that of the CON group (*** p < 0.001), and HMF treatment suppressed its increase (#p < 0.05). TNF-α mRNA and iNOS mRNA expression were not increased by LPS, and the treatment with HMF did not change its level. COX-2 mRNA expression in the LPS group was higher than that of the CON group, but not significant (p = 0.052), and this increment showed the tendency to suppress by the treatment of HMF at the concentration of 100 mg/kg/day (p = 0.056; Figure 4A).


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 mRNAs for inflammatory markers in the hippocampus. Hippocampal tissues were prepared two days after LPS intrahippocampal injection, and RT-PCR analysis was performed with specific primers. Densitometric quantification of mRNAs of COX-2 (A), IL-1β (B), TNF-α (C) and iNOS (D) band intensities normalized by the β-actin mRNA band in the hippocampus. Values are the means ± SEM. Symbols are significantly different for the following conditions: CON vs. LPS, *** p < 0.001; 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-f004: Effects of HMF on the expression of mRNAs for inflammatory markers in the hippocampus. Hippocampal tissues were prepared two days after LPS intrahippocampal injection, and RT-PCR analysis was performed with specific primers. Densitometric quantification of mRNAs of COX-2 (A), IL-1β (B), TNF-α (C) and iNOS (D) band intensities normalized by the β-actin mRNA band in the hippocampus. Values are the means ± SEM. Symbols are significantly different for the following conditions: CON vs. LPS, *** p < 0.001; LPS vs. LPS + HMF100, #p < 0.05.
Mentions: As activated microglia are known to contribute to neurodegenerative processes by producing various cytotoxic molecules, including proinflammatory cytokines [18,19,20], we examined the effects of HMF on the LPS-induced gene expression of proinflammatory cytokines (IL-1β and TNF-α) and enzyme (iNOS and COX-2) with RT-PCR. Figure 4B shows that IL-1β mRNA expression in the LPS group was significantly higher than that of the CON group (*** p < 0.001), and HMF treatment suppressed its increase (#p < 0.05). TNF-α mRNA and iNOS mRNA expression were not increased by LPS, and the treatment with HMF did not change its level. COX-2 mRNA expression in the LPS group was higher than that of the CON group, but not significant (p = 0.052), and this increment showed the tendency to suppress by the treatment of HMF at the concentration of 100 mg/kg/day (p = 0.056; Figure 4A).

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