Quercetin attenuates high fat diet-induced atherosclerosis in apolipoprotein E knockout mice: A critical role of NADPH oxidase

Food Chem Toxicol. 2017 Jul:105:22-33. doi: 10.1016/j.fct.2017.03.048. Epub 2017 Mar 27.

Abstract

Reactive oxygen species (ROS) have emerged as important molecules in cardiovascular function. Nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase is the major source of ROS in phagocytic and vascular cells. Several lines of evidence indicate that quercetin contributes to protecting against atherosclerosis. Herein, we investigated the effect of quercetin on alleviating atherosclerosis by regulating NADPH oxidase subunits expression in vivo, and explored the mechanism of quercetin suppressing the ROS overproduction stimulated by ox-LDL in mouse peritoneal macrophages (MPMs). Model ApoE KO mice were fed with either a normal chow diet or a high fat diet (HFD) supplemented with or without dosed quercetin for 24 weeks. Quercetin significantly reduced the atherosclerotic plaque area, alleviated the systemic oxidative stress, and suppressed aortic p47phox, p67phox expressions but partially reversed the NOX4 expression as compared to those in the HFD group. In vitro, quercetin effectively inhibited the ox-LDL induced ROS formation in MPMs, and blocked the vital step in activation of NADPH oxidase - membrane translocation of p47phox. Our findings suggest that regular consumption of dietary quercetin plays a role in preventing atherosclerosis giving its evident regulatory effect on subunits of NADPH oxidase.

Keywords: Atherosclerosis; NADPH oxidase; Oxidative stress; Quercetin; Reactive oxygen species; p47phox.

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Apolipoproteins E / deficiency*
  • Apolipoproteins E / genetics
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / enzymology*
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Diet, High-Fat / adverse effects
  • Humans
  • Lipoproteins, LDL / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • NADPH Oxidases / genetics
  • NADPH Oxidases / metabolism*
  • Oxidation-Reduction
  • Phosphoproteins
  • Quercetin / pharmacology*
  • Reactive Oxygen Species / metabolism

Substances

  • Apolipoproteins E
  • Lipoproteins, LDL
  • Phosphoproteins
  • Reactive Oxygen Species
  • neutrophil cytosol factor 67K
  • oxidized low density lipoprotein
  • Quercetin
  • NADPH Oxidases
  • neutrophil cytosolic factor 1