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Evidence-Based Complementary and Alternative Medicine
Volume 2012 (2012), Article ID 639469, 10 pages
http://dx.doi.org/10.1155/2012/639469
Research Article

Fisetin Inhibits Hyperglycemia-Induced Proinflammatory Cytokine Production by Epigenetic Mechanisms

1Pharmacology Research Center, Korea Research Institute of Chemical Technology, Daejeon 305-600, Republic of Korea
2Department of Food and Nutrition, Kwangju Women’s University, 165 Sanjeong Dong, Gwangsan-Gu, Gwangju 506-713, Republic of Korea

Received 5 October 2012; Accepted 3 December 2012

Academic Editor: Menaka C. Thounaojam

Copyright © 2012 Hye Joo Kim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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- B 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  M) for 48 h. While the HG condition significantly induced histone acetylation, NF- B activation, and proinflammatory cytokine (IL-6 and TNF- ) release from THP-1 cells, fisetin suppressed NF- B 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- B coactivator. These results suggest that fisetin inhibits HG-induced cytokine production in monocytes, through epigenetic changes involving NF- B. We therefore propose that fisetin supplementation be considered for diabetes prevention.