Fisetin Inhibits Hyperglycemia-Induced Proinflammatory Cytokine Production by Epigenetic Mechanisms

• Published in: Evidence-based complementary and alternative medicine 2012-01, Vol.2012 (2012), p.1-10
• Main Authors: Kim, Hye Joo, Yun, Jung-Mi, Kim, Seong Hwan
• Format: Article
• Language: English
• Subjects: Acetylation; Biochemistry; Biology; CBP/p300 protein; Chromatin; Complications; Cytokines; Deoxyribonucleic acid; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes mellitus (non-insulin dependent); Dietary supplements; Disease control; DNA; DNA methylation; Epigenetics; Event-related potentials; Flavonoids; Fruits; Gene expression; Glucose; Hyperglycemia; Inflammation; Interleukin 6; Mannitol; Medical research; Monocytes; Oxidative stress; p300 Protein; Signal transduction; Smoke; Transcription factors; Tumor necrosis factor; Tumor necrosis factor-TNF
• ISSN: 1741-427X; 1741-4288
• DOI: 10.1155/2012/639469

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.