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Fisetin Suppresses Macrophage-Mediated Inflammatory Responses by Blockade of Src and Syk.

Kim JH, Kim MY, Kim JH, Cho JY - Biomol Ther (Seoul) (2015)

Bottom Line: In agreement, the upstream phosphorylation events for NF-κB activation, composed of Src, Syk, and IκBα, were also reduced by fisetin.The phospho-Src level, triggered by overexpression of wild-type Src, was also inhibited by fisetin.Therefore, these results strongly suggest that fisetin can be considered a bioactive immunomodulatory compound with anti-inflammatory properties through suppression of Src and Syk activities.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746.

ABSTRACT
Flavonoids, such as fisetin (3,7,3',4'-tetrahydroxyflavone), are plant secondary metabolites. It has been reported that fisetin is able to perform numerous pharmacological roles including anti-inflammatory, anti-microbial, and anti-cancer activities; however, the exact anti-inflammatory mechanism of fisetin is not understood. In this study, the pharmacological action modes of fisetin in lipopolysaccharide (LPS)-stimulated macrophage-like cells were elucidated by using immunoblotting analysis, kinase assays, and an overexpression strategy. Fisetin diminished the release of nitric oxide (NO) and reduced the mRNA levels of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-α, and cyclooxygenase (COX)-2 in LPS-stimulated RAW264.7 cells without displaying cytotoxicity. This compound also blocked the nuclear translocation of p65/nuclear factor (NF)-κB. In agreement, the upstream phosphorylation events for NF-κB activation, composed of Src, Syk, and IκBα, were also reduced by fisetin. The phospho-Src level, triggered by overexpression of wild-type Src, was also inhibited by fisetin. Therefore, these results strongly suggest that fisetin can be considered a bioactive immunomodulatory compound with anti-inflammatory properties through suppression of Src and Syk activities.

No MeSH data available.


Related in: MedlinePlus

The effect of fisetin on the upstream signaling cascade of NF-κB. (A and B) RAW264.7 cells were incubated with LPS (1 μg/mL) in the presence or absence of fisetin (30 μM) for 30 min. The total phospho-protein levels of Src, Syk, and IκBα from whole lysates were determined by immunoblotting analysis.
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f4-bt-23-414: The effect of fisetin on the upstream signaling cascade of NF-κB. (A and B) RAW264.7 cells were incubated with LPS (1 μg/mL) in the presence or absence of fisetin (30 μM) for 30 min. The total phospho-protein levels of Src, Syk, and IκBα from whole lysates were determined by immunoblotting analysis.

Mentions: Many studies have demonstrated that the NF-κB pathway is regulated by intracellular signaling cascades (Byeon et al., 2012; Yi et al., 2014). These signaling cascades include Src, Syk, and IκBα. To identify fisetin-targeted molecules in this pathway, we confirmed the expression levels of these molecules by immunoblotting analysis. Expectedly, the phospho-IκBα level in fisetin-treated cells was clearly decreased at 5, 30, and 60 min (Fig. 4A). Also, the autophosphorylation levels of Src and Syk were strikingly suppressed by fisetin at 2 min, without decreasing total levels of Src and Syk (Fig. 4B).


Fisetin Suppresses Macrophage-Mediated Inflammatory Responses by Blockade of Src and Syk.

Kim JH, Kim MY, Kim JH, Cho JY - Biomol Ther (Seoul) (2015)

The effect of fisetin on the upstream signaling cascade of NF-κB. (A and B) RAW264.7 cells were incubated with LPS (1 μg/mL) in the presence or absence of fisetin (30 μM) for 30 min. The total phospho-protein levels of Src, Syk, and IκBα from whole lysates were determined by immunoblotting analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556200&req=5

f4-bt-23-414: The effect of fisetin on the upstream signaling cascade of NF-κB. (A and B) RAW264.7 cells were incubated with LPS (1 μg/mL) in the presence or absence of fisetin (30 μM) for 30 min. The total phospho-protein levels of Src, Syk, and IκBα from whole lysates were determined by immunoblotting analysis.
Mentions: Many studies have demonstrated that the NF-κB pathway is regulated by intracellular signaling cascades (Byeon et al., 2012; Yi et al., 2014). These signaling cascades include Src, Syk, and IκBα. To identify fisetin-targeted molecules in this pathway, we confirmed the expression levels of these molecules by immunoblotting analysis. Expectedly, the phospho-IκBα level in fisetin-treated cells was clearly decreased at 5, 30, and 60 min (Fig. 4A). Also, the autophosphorylation levels of Src and Syk were strikingly suppressed by fisetin at 2 min, without decreasing total levels of Src and Syk (Fig. 4B).

Bottom Line: In agreement, the upstream phosphorylation events for NF-κB activation, composed of Src, Syk, and IκBα, were also reduced by fisetin.The phospho-Src level, triggered by overexpression of wild-type Src, was also inhibited by fisetin.Therefore, these results strongly suggest that fisetin can be considered a bioactive immunomodulatory compound with anti-inflammatory properties through suppression of Src and Syk activities.

View Article: PubMed Central - PubMed

Affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746.

ABSTRACT
Flavonoids, such as fisetin (3,7,3',4'-tetrahydroxyflavone), are plant secondary metabolites. It has been reported that fisetin is able to perform numerous pharmacological roles including anti-inflammatory, anti-microbial, and anti-cancer activities; however, the exact anti-inflammatory mechanism of fisetin is not understood. In this study, the pharmacological action modes of fisetin in lipopolysaccharide (LPS)-stimulated macrophage-like cells were elucidated by using immunoblotting analysis, kinase assays, and an overexpression strategy. Fisetin diminished the release of nitric oxide (NO) and reduced the mRNA levels of inducible NO synthase (iNOS), tumor necrosis factor (TNF)-α, and cyclooxygenase (COX)-2 in LPS-stimulated RAW264.7 cells without displaying cytotoxicity. This compound also blocked the nuclear translocation of p65/nuclear factor (NF)-κB. In agreement, the upstream phosphorylation events for NF-κB activation, composed of Src, Syk, and IκBα, were also reduced by fisetin. The phospho-Src level, triggered by overexpression of wild-type Src, was also inhibited by fisetin. Therefore, these results strongly suggest that fisetin can be considered a bioactive immunomodulatory compound with anti-inflammatory properties through suppression of Src and Syk activities.

No MeSH data available.


Related in: MedlinePlus