title: Quercetin attenuates high fructose feeding-induced atherosclerosis by suppressing inflammation and apoptosis via ROS-regulated PI3K/AKT signaling pathway.
abstract: Quercetin is a dietary flavonoid compound extracted from various plants, such as apple and onions. Previous studies have revealed its anti-inflammatory, anti-cancer, antioxidant and anti-apoptotic activities. This study investigated the ability of quercetin to inhibit high fructose feeding- or LPS-induced atherosclerosis through regulating oxidative stress, apoptosis and inflammation response in vivo and in vitro experiments. 50 and 100mg/kg quercetin were used in our study, showing significant inhibitory role in high fructose-induced atherosclerosis via reducing reactive oxygen species (ROS) levels, Caspase-3 activation, inflammatory cytokines releasing, the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells and collagen contents as well as modulating apoptosis- and inflammation-related proteins expression. We also explored the protective effects of quercetin on atherosclerosis by phosphatidylinositide 3-kinases (PI3K)/Protein kinase B (AKT)-associated Bcl-2/Caspase-3 and nuclear factor kappa B (NF-κB) signal pathways activation, promoting AKT and Bcl-2 expression and reducing Caspase-3 and NF-κB activation. Quercetin reduced the atherosclerotic plaque size in vivo in high fructose feeding-induced mice assessed by oil red O. Also, in vitro experiments, quercetin displayed inhibitory role in LPS-induced ROS production, inflammatory response and apoptosis, which were linked with PI3K/AKT-regulated Caspase-3 and NF-κB activation. In conclusion, our results showed that quercetin inhibited atherosclerotic plaque development in high fructose feeding mice via PI3K/AKT activation regulated by ROS.
authors.affiliation: Department of Cardiology, Huaihe Hospital, Henan University, Kaifeng 475000, China. Electronic address: luxli123@126.com.
authors.forename: Xue-Li
authors.initials: XL
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Huaihe Hospital, Henan University, Kaifeng 475000, China.
authors.forename: Cui-Hua
authors.initials: CH
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Huaihe Hospital, Henan University, Kaifeng 475000, China.
authors.forename: Xin-Liang
authors.initials: XL
authors.lastname: Yao
authors.affiliation: Department of Cardiology, Huaihe Hospital, Henan University, Kaifeng 475000, China.
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000821:Animal Feed; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D050197:Atherosclerosis / Q000139:chemically induced / Q000517:prevention & control*; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000008:administration & dosage / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D005951:Glucose Tolerance Test; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011794:Quercetin / Q000008:administration & dosage / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D004040:Dietary Carbohydrates; D017382:Reactive Oxygen Species; D005632:Fructose; D011794:Quercetin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Atherosclerosis; High fructose; PI3K/AKT; Quercetin; ROS