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Fisetin inhibits hyperglycemia-induced proinflammatory cytokine production by epigenetic mechanisms.

Kim HJ, Kim SH, Yun JM - Evid Based Complement Alternat Med (2012)

Bottom Line: Fisetin, a flavonoid dietary ingredient found in the smoke tree (Cotinus coggygria), and is also widely distributed in fruits and vegetables.Fisetin is known to exert anti-inflammatory effects via inhibition of the NF-κB signaling pathway.These results suggest that fisetin inhibits HG-induced cytokine production in monocytes, through epigenetic changes involving NF-κB.

View Article: PubMed Central - PubMed

Affiliation: Pharmacology Research Center, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.

ABSTRACT
Diabetes is characterized by a proinflammatory state, and several inflammatory processes have been associated with both type 1 and type 2 diabetes and the resulting complications. High glucose levels induce the release of proinflammatory cytokines. Fisetin, a flavonoid dietary ingredient found in the smoke tree (Cotinus coggygria), and is also widely distributed in fruits and vegetables. Fisetin is known to exert anti-inflammatory effects via inhibition of the NF-κB signaling pathway. In this study, we analyzed the effects of fisetin on proinflammatory cytokine secretion and epigenetic regulation, in human monocytes cultured under hyperglycemic conditions. Human monocytic (THP-1) cells were cultured under control (14.5 mmol/L mannitol), normoglycemic (NG, 5.5 mmol/L glucose), or hyperglycemic (HG, 20 mmol/L glucose) conditions, in the absence or presence of fisetin. Fisetin was added (3-10 μM) for 48 h. While the HG condition significantly induced histone acetylation, NF-κB activation, and proinflammatory cytokine (IL-6 and TNF-α) release from THP-1 cells, fisetin suppressed NF-κB activity and cytokine release. Fisetin treatment also significantly reduced CBP/p300 gene expression, as well as the levels of acetylation and HAT activity of the CBP/p300 protein, which is a known NF-κB coactivator. These results suggest that fisetin inhibits HG-induced cytokine production in monocytes, through epigenetic changes involving NF-κB. We therefore propose that fisetin supplementation be considered for diabetes prevention.

No MeSH data available.


Related in: MedlinePlus

The cytotoxicity of fisetin to cultured high glucose-induced THP-1 cells. (a) Chemical structure of fisetin. (b) Effect of fisetin on cell viability after 48 h was evaluated by the CCK-8 assay, as described in the methods. Human monocytic (THP-1) cells (1 × 105 cells/mL) were cultured in presence of osmolar control (14.5 mmol/L mannitol) or normal glycemic (NG, 5.5 mmol/L glucose) or hyperglycemic (HG, 20 mmol/L) conditions in absence or presence of fisetin (0, 3, 6, 10 μM) for 48 h as described in the methods and the media was collected. Results are shown as mean ± SD of five different experiments.
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fig1: The cytotoxicity of fisetin to cultured high glucose-induced THP-1 cells. (a) Chemical structure of fisetin. (b) Effect of fisetin on cell viability after 48 h was evaluated by the CCK-8 assay, as described in the methods. Human monocytic (THP-1) cells (1 × 105 cells/mL) were cultured in presence of osmolar control (14.5 mmol/L mannitol) or normal glycemic (NG, 5.5 mmol/L glucose) or hyperglycemic (HG, 20 mmol/L) conditions in absence or presence of fisetin (0, 3, 6, 10 μM) for 48 h as described in the methods and the media was collected. Results are shown as mean ± SD of five different experiments.

Mentions: The chemical structure of fisetin is shown in Figure 1(a). We investigated the cytotoxic effect of fisetin on high glucose-induced THP-1 cells, using CCK-8 assay (Figure 1(b)). No toxicity was observed at concentrations of fisetin between 3 and 10 μM, for 48 h of treatment. All our experiments were performed in the latter, nontoxic concentration range of fisetin (Figure 1(b)).


Fisetin inhibits hyperglycemia-induced proinflammatory cytokine production by epigenetic mechanisms.

Kim HJ, Kim SH, Yun JM - Evid Based Complement Alternat Med (2012)

The cytotoxicity of fisetin to cultured high glucose-induced THP-1 cells. (a) Chemical structure of fisetin. (b) Effect of fisetin on cell viability after 48 h was evaluated by the CCK-8 assay, as described in the methods. Human monocytic (THP-1) cells (1 × 105 cells/mL) were cultured in presence of osmolar control (14.5 mmol/L mannitol) or normal glycemic (NG, 5.5 mmol/L glucose) or hyperglycemic (HG, 20 mmol/L) conditions in absence or presence of fisetin (0, 3, 6, 10 μM) for 48 h as described in the methods and the media was collected. Results are shown as mean ± SD of five different experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539716&req=5

fig1: The cytotoxicity of fisetin to cultured high glucose-induced THP-1 cells. (a) Chemical structure of fisetin. (b) Effect of fisetin on cell viability after 48 h was evaluated by the CCK-8 assay, as described in the methods. Human monocytic (THP-1) cells (1 × 105 cells/mL) were cultured in presence of osmolar control (14.5 mmol/L mannitol) or normal glycemic (NG, 5.5 mmol/L glucose) or hyperglycemic (HG, 20 mmol/L) conditions in absence or presence of fisetin (0, 3, 6, 10 μM) for 48 h as described in the methods and the media was collected. Results are shown as mean ± SD of five different experiments.
Mentions: The chemical structure of fisetin is shown in Figure 1(a). We investigated the cytotoxic effect of fisetin on high glucose-induced THP-1 cells, using CCK-8 assay (Figure 1(b)). No toxicity was observed at concentrations of fisetin between 3 and 10 μM, for 48 h of treatment. All our experiments were performed in the latter, nontoxic concentration range of fisetin (Figure 1(b)).

Bottom Line: Fisetin, a flavonoid dietary ingredient found in the smoke tree (Cotinus coggygria), and is also widely distributed in fruits and vegetables.Fisetin is known to exert anti-inflammatory effects via inhibition of the NF-κB signaling pathway.These results suggest that fisetin inhibits HG-induced cytokine production in monocytes, through epigenetic changes involving NF-κB.

View Article: PubMed Central - PubMed

Affiliation: Pharmacology Research Center, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea.

ABSTRACT
Diabetes is characterized by a proinflammatory state, and several inflammatory processes have been associated with both type 1 and type 2 diabetes and the resulting complications. High glucose levels induce the release of proinflammatory cytokines. Fisetin, a flavonoid dietary ingredient found in the smoke tree (Cotinus coggygria), and is also widely distributed in fruits and vegetables. Fisetin is known to exert anti-inflammatory effects via inhibition of the NF-κB signaling pathway. In this study, we analyzed the effects of fisetin on proinflammatory cytokine secretion and epigenetic regulation, in human monocytes cultured under hyperglycemic conditions. Human monocytic (THP-1) cells were cultured under control (14.5 mmol/L mannitol), normoglycemic (NG, 5.5 mmol/L glucose), or hyperglycemic (HG, 20 mmol/L glucose) conditions, in the absence or presence of fisetin. Fisetin was added (3-10 μM) for 48 h. While the HG condition significantly induced histone acetylation, NF-κB activation, and proinflammatory cytokine (IL-6 and TNF-α) release from THP-1 cells, fisetin suppressed NF-κB activity and cytokine release. Fisetin treatment also significantly reduced CBP/p300 gene expression, as well as the levels of acetylation and HAT activity of the CBP/p300 protein, which is a known NF-κB coactivator. These results suggest that fisetin inhibits HG-induced cytokine production in monocytes, through epigenetic changes involving NF-κB. We therefore propose that fisetin supplementation be considered for diabetes prevention.

No MeSH data available.


Related in: MedlinePlus