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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

Effect of fisetin on the interaction of p300 with acetylated p65 and TNF-α. Cells were treated with fisetin for 48 h and then nuclear lysates were prepared. p300 was immunoprecipitated, and interaction with acetylated p65 and TNF-α was assessed by western blotting. The immunoblots shown here are representative of 3 independent experiments.
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fig5: Effect of fisetin on the interaction of p300 with acetylated p65 and TNF-α. Cells were treated with fisetin for 48 h and then nuclear lysates were prepared. p300 was immunoprecipitated, and interaction with acetylated p65 and TNF-α was assessed by western blotting. The immunoblots shown here are representative of 3 independent experiments.

Mentions: To further understand the mechanism of fisetin-mediated inhibition of inflammation, we investigated its effect on the interaction between p300 and NF-κB. As shown in Figure 5, fisetin reduced the interaction of p300 with both the acetylated form of NF-κB and with TNF-α. This was associated with decreased TNF-α gene transcription in monocytes under HG conditions.


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

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

Effect of fisetin on the interaction of p300 with acetylated p65 and TNF-α. Cells were treated with fisetin for 48 h and then nuclear lysates were prepared. p300 was immunoprecipitated, and interaction with acetylated p65 and TNF-α was assessed by western blotting. The immunoblots shown here are representative of 3 independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: Effect of fisetin on the interaction of p300 with acetylated p65 and TNF-α. Cells were treated with fisetin for 48 h and then nuclear lysates were prepared. p300 was immunoprecipitated, and interaction with acetylated p65 and TNF-α was assessed by western blotting. The immunoblots shown here are representative of 3 independent experiments.
Mentions: To further understand the mechanism of fisetin-mediated inhibition of inflammation, we investigated its effect on the interaction between p300 and NF-κB. As shown in Figure 5, fisetin reduced the interaction of p300 with both the acetylated form of NF-κB and with TNF-α. This was associated with decreased TNF-α gene transcription in monocytes under HG conditions.

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