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KMID : 1161420170200080782
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Journal of Medicinal Food
2017 Volume.20 No. 8 p.782 ~ p.789
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Combination Treatments with Luteolin and Fisetin Enhance Anti-Inflammatory Effects in High Glucose-Treated THP-1 Cells Through Histone Acetyltransferase/Histone Deacetylase Regulation
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Kim A-Rang
Yun Jung-Mi
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Abstract
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Hyperglycemia leads to diabetes and its diabetic complications. In this study, we investigated the synergistic effects of luteolin and fisetin on proinflammatory cytokine secretion and its underlying epigenetic regulation in human monocytes exposed to hyperglycemic (HG) concentrations. Human monocytic cells (THP-1) were cultured under controlled (14.5?mM mannitol), normoglycemic (5.5?mM glucose), or HG (20?mM glucose) conditions in the absence or presence of the two phytochemicals for 48?h. Whereas HG conditions significantly induced histone acetylation, nuclear factor-kappa B (NF-κB) activation, interleukin 6, and tumor necrosis factor?α release from THP-1 cells; combination treatments with the two phytochemicals (500?nM fisetin, and l μM and 500?nM luteolin) suppressed NF-κB activity and inflammatory cytokine release. Fisetin, luteolin, and their combination treatments also significantly decreased the activity of histone acetyltransferase, a known NF-κB coactivator; inhibited reactive oxygen species production; and activated sirtuin (SIRT)1 and forkhead box O3a (FOXO3a) expressions (P?
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KEYWORD
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diabetes, epigenetics, fisetin, HDAC, luteolin
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