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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.


Structure of 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF).
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brainsci-05-00118-f001: Structure of 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF).

Mentions: Among natural materials, citrus fruits are some of the most popular fruits worldwide and are known to be a rich source of bioactive compounds, including flavonoids, coumarins, limonoids and carotenoids. Particularly in flavonoids, polymethoxylated flavones (PMFs) and hydroxylated polymethoxyflavones are sure to be the focus of recent attention, because of their broad spectrum of biological activities [7]. PMFs were shown to have anti-inflammatory effects in peripheral tissues, for example: (1) 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF; Figure 1) exhibited anti-inflammatory effects on isolated human monocytes that were mediated by the inhibition of phosphodiesterase (PDE)-4 and cytokine production [8]; (2) 5,6,7,8,3′,4′-hexamethoxyflavone (nobiletin; NBT) attenuated lipopolysaccharide (LPS)-induced inflammatory factors in human synovial fibroblasts and mouse macrophages [9]; (3) 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone inhibited 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced skin inflammation and tumor promotion in mice [10]; (4) 5,6,7,8,3′,4′,-hexamethoxy-3-hydroxyflavone (natsudaidain) inhibited the expression of tumor necrosis factor (TNF)-α and cyclooxygenase (COX)-2 in Ca2+ ionophore-stimulated rat basophilic leukemia cells (A23187-stimulated RBL-2H3 cells) [11]; and (5) 5,7,4′-trihydroxy-6,8,3′-trimethoxyflavone (sudachitin) suppressed the expression of TNF-α and the production of nitric oxide (NO) in LPS-stimulated RAW264 cells, a macrophage-derived mouse cell line [12]. Recent in vitro studies suggested that HMF may have also anti-inflammatory effects in CNS-related cells; that is, HMF has been shown to inhibit the production of NO and inducible nitric oxide synthase (iNOS) in cultured astrocytes, which are involved in supporting neurons in the CNS [13]. In our in vivo study, HMF suppressed the microglia activation in the hippocampus following ischemia and protected from neuronal cell death [14]. Therefore, the aim of the present study was to investigate whether HMF exhibited anti-inflammatory activity in the LPS-injected brain.


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)

Structure of 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF).
© Copyright Policy
Related In: Results  -  Collection

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

brainsci-05-00118-f001: Structure of 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF).
Mentions: Among natural materials, citrus fruits are some of the most popular fruits worldwide and are known to be a rich source of bioactive compounds, including flavonoids, coumarins, limonoids and carotenoids. Particularly in flavonoids, polymethoxylated flavones (PMFs) and hydroxylated polymethoxyflavones are sure to be the focus of recent attention, because of their broad spectrum of biological activities [7]. PMFs were shown to have anti-inflammatory effects in peripheral tissues, for example: (1) 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF; Figure 1) exhibited anti-inflammatory effects on isolated human monocytes that were mediated by the inhibition of phosphodiesterase (PDE)-4 and cytokine production [8]; (2) 5,6,7,8,3′,4′-hexamethoxyflavone (nobiletin; NBT) attenuated lipopolysaccharide (LPS)-induced inflammatory factors in human synovial fibroblasts and mouse macrophages [9]; (3) 5-hydroxy-3,6,7,8,3′,4′-hexamethoxyflavone inhibited 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced skin inflammation and tumor promotion in mice [10]; (4) 5,6,7,8,3′,4′,-hexamethoxy-3-hydroxyflavone (natsudaidain) inhibited the expression of tumor necrosis factor (TNF)-α and cyclooxygenase (COX)-2 in Ca2+ ionophore-stimulated rat basophilic leukemia cells (A23187-stimulated RBL-2H3 cells) [11]; and (5) 5,7,4′-trihydroxy-6,8,3′-trimethoxyflavone (sudachitin) suppressed the expression of TNF-α and the production of nitric oxide (NO) in LPS-stimulated RAW264 cells, a macrophage-derived mouse cell line [12]. Recent in vitro studies suggested that HMF may have also anti-inflammatory effects in CNS-related cells; that is, HMF has been shown to inhibit the production of NO and inducible nitric oxide synthase (iNOS) in cultured astrocytes, which are involved in supporting neurons in the CNS [13]. In our in vivo study, HMF suppressed the microglia activation in the hippocampus following ischemia and protected from neuronal cell death [14]. Therefore, the aim of the present study was to investigate whether HMF exhibited anti-inflammatory activity in the LPS-injected brain.

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.