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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 chromatin event at the promoter of inflammatory gene. ChIP assays were performed using MAGnify ChIP according to the manufacturer's instructions. Immunoprecipitations were performed overnight at 4°C with 5 μg of p300 antibody. DNA was subjected to PCR. ChIP assays showed the recruitment of p300 to the TNF-α promoters. Results of 1 typical experiment of 3 are shown. Values from ChIP with anti-p300 antibody represent the fold difference relative to those from IgG control antibody. ††P < 0.01 compared to NG; *P < 0.05; **P < 0.01 compared to HG. Results are shown as mean ± SD for 3 different experiments.
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fig6: Effect of fisetin on chromatin event at the promoter of inflammatory gene. ChIP assays were performed using MAGnify ChIP according to the manufacturer's instructions. Immunoprecipitations were performed overnight at 4°C with 5 μg of p300 antibody. DNA was subjected to PCR. ChIP assays showed the recruitment of p300 to the TNF-α promoters. Results of 1 typical experiment of 3 are shown. Values from ChIP with anti-p300 antibody represent the fold difference relative to those from IgG control antibody. ††P < 0.01 compared to NG; *P < 0.05; **P < 0.01 compared to HG. Results are shown as mean ± SD for 3 different experiments.

Mentions: To confirm the epigenetic regulation of fisetin on inflammation, we next used ChIP assays to further investigate whether p300 can be bound to the promoters of NF-κB-related inflammatory cytokine genes under HG conditions. ChIP assays showed that HG increased the recruitment of p300 to the TNF-α promoter. As shown in Figure 6, Fisetin reduced the binding of p300 to the promoter region of TNF-α. This was associated with decreased TNF 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 chromatin event at the promoter of inflammatory gene. ChIP assays were performed using MAGnify ChIP according to the manufacturer's instructions. Immunoprecipitations were performed overnight at 4°C with 5 μg of p300 antibody. DNA was subjected to PCR. ChIP assays showed the recruitment of p300 to the TNF-α promoters. Results of 1 typical experiment of 3 are shown. Values from ChIP with anti-p300 antibody represent the fold difference relative to those from IgG control antibody. ††P < 0.01 compared to NG; *P < 0.05; **P < 0.01 compared to HG. Results are shown as mean ± SD for 3 different experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig6: Effect of fisetin on chromatin event at the promoter of inflammatory gene. ChIP assays were performed using MAGnify ChIP according to the manufacturer's instructions. Immunoprecipitations were performed overnight at 4°C with 5 μg of p300 antibody. DNA was subjected to PCR. ChIP assays showed the recruitment of p300 to the TNF-α promoters. Results of 1 typical experiment of 3 are shown. Values from ChIP with anti-p300 antibody represent the fold difference relative to those from IgG control antibody. ††P < 0.01 compared to NG; *P < 0.05; **P < 0.01 compared to HG. Results are shown as mean ± SD for 3 different experiments.
Mentions: To confirm the epigenetic regulation of fisetin on inflammation, we next used ChIP assays to further investigate whether p300 can be bound to the promoters of NF-κB-related inflammatory cytokine genes under HG conditions. ChIP assays showed that HG increased the recruitment of p300 to the TNF-α promoter. As shown in Figure 6, Fisetin reduced the binding of p300 to the promoter region of TNF-α. This was associated with decreased TNF 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