title: Quercetin is a potent anti-atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation.
abstract: METHODS
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.|Institute of Allied Health Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Ching-Hsia
authors.initials: CH
authors.lastname: Hung
authors.affiliation: Department of Internal Medicine, College of Medicine and Hospital, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shih-Hung
authors.initials: SH
authors.lastname: Chan
authors.affiliation: Department of Anatomy, School of Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Pei-Ming
authors.initials: PM
authors.lastname: Chu
authors.affiliation: Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Kun-Ling
authors.initials: KL
authors.lastname: Tsai
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C099252:oxidized low density lipoprotein; D011794:Quercetin; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: AMPK; Endothelial dysfunction; Inflammation; OxLDL; SIRT1