Limits...
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

Fisetin-induced suppression of NF-κB activation in HG-treated THP-1 cells. Protein levels were evaluated by western blot for NF-κB p65 and acetylated p65. Equal loading of protein was confirmed by stripping the immunoblot and reprobing it for histone 2A protein. The immunoblots shown here are representative of 3 independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3539716&req=5

fig4: Fisetin-induced suppression of NF-κB activation in HG-treated THP-1 cells. Protein levels were evaluated by western blot for NF-κB p65 and acetylated p65. Equal loading of protein was confirmed by stripping the immunoblot and reprobing it for histone 2A protein. The immunoblots shown here are representative of 3 independent experiments.

Mentions: Histone acetylation is associated with increased NF-κB activation that leads to increased acetylation of the RelA/p65 subunit of NF-κB [3]. Therefore, we studied the effect of fisetin on acetylation of p65 and subsequent NF-κB activation, under high-glucose conditions. We observed that fisetin resulted in significantly decreased acetylation and phosphorylation of NF-κBp65 in the nuclear faction (Figure 4).


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

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

Fisetin-induced suppression of NF-κB activation in HG-treated THP-1 cells. Protein levels were evaluated by western blot for NF-κB p65 and acetylated p65. Equal loading of protein was confirmed by stripping the immunoblot and reprobing it for histone 2A protein. 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

fig4: Fisetin-induced suppression of NF-κB activation in HG-treated THP-1 cells. Protein levels were evaluated by western blot for NF-κB p65 and acetylated p65. Equal loading of protein was confirmed by stripping the immunoblot and reprobing it for histone 2A protein. The immunoblots shown here are representative of 3 independent experiments.
Mentions: Histone acetylation is associated with increased NF-κB activation that leads to increased acetylation of the RelA/p65 subunit of NF-κB [3]. Therefore, we studied the effect of fisetin on acetylation of p65 and subsequent NF-κB activation, under high-glucose conditions. We observed that fisetin resulted in significantly decreased acetylation and phosphorylation of NF-κBp65 in the nuclear faction (Figure 4).

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