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Quercetin is a potent anti‐atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation
Author(s) -
Hung ChingHsia,
Chan ShihHung,
Chu PeiMing,
Tsai KunLing
Publication year - 2015
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201500144
Subject(s) - quercetin , nadph oxidase , sirtuin 1 , oxidative stress , chemistry , nicotinamide adenine dinucleotide phosphate , ampk , nox4 , protein kinase b , endothelial dysfunction , reactive oxygen species , oxidative phosphorylation , umbilical vein , nad(p)h oxidase , pharmacology , biochemistry , protein kinase a , signal transduction , oxidase test , kinase , endocrinology , biology , antioxidant , downregulation and upregulation , enzyme , in vitro , gene
Scope Atherosclerosis is believed to be an independent predictor of cardiovascular diseases. A growing body of evidence suggests that quercetin is a potent antioxidant and anti‐inflammatory compound. The molecular mechanisms underlying its protective effects against oxidative stress in human endothelial cells remain unclear. This study was designed to confirm the hypothesis that quercetin inhibits oxidized LDL (oxLDL) induced endothelial oxidative damage by activating sirtuin 1 (SIRT1) and to explore the role of adenosine monophosphate activated protein kinase (AMPK), which is a negative regulator of Nicotinamide adenine dinucleotide phosphate‐oxidase (NADPH oxidase) and free radicals. Methods and results Human umbilical vein endothelial cells were treated with oxLDL with or without quercetin pretreatment. We found that quercetin pretreatment increased SIRT1 mRNA expression. In fact, quercetin protected against oxLDL‐impaired SIRT1 and AMPK activities and reduced oxLDL‐activated NOX2 and NOX4. However, silencing SIRT1 and AMPK diminished the protective function of quercetin against oxidative injuries. The results also indicated that oxLDL suppressed AKT/endothelial NO synthase, impaired mitochondrial dysfunction, and enhanced reactive oxygen species formation, activating the Nuclear Factor Kappa B (NF‐κB) pathway. Conclusion These results provide new insight regarding the possible molecular mechanisms of quercetin. Quercetin suppresses oxLDL‐induced endothelial oxidative injuries by activating SIRT1 and modulating the AMPK/NADPH oxidase/AKT/endothelial NO synthase signaling pathway.