title: Apple Polyphenols Decrease Atherosclerosis and Hepatic Steatosis in ApoE-/- Mice through the ROS/MAPK/NF-κB Pathway.
abstract: In this study, we examined the effects of apple polyphenols (APs) on hyperlipidemia, atherosclerosis, hepatic steatosis and endothelial function and investigated the potential mechanisms. ApoE(-/-) mice were fed a western-type diet and orally treated with APs (100 mg/kg) or atorvastatin (10 mg/kg) for 12 weeks. Hyperlipidemia and atherosclerosis in the aortic sinuses and, and hepatic lipidosis were measured. The treatment with APs or atorvastatin induced a remarkable reduction in the atherosclerotic lesions and hepatic steatosis and decreased the levels of low-density lipoprotein, triglyceride, CCL-2 and VCAM-1 levels in the plasma. Conversely, the APs significantly increased the plasma levels of high-density lipoprotein (HDL) cholesterol and markedly up-regulated the glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) levels in liver tissues. Moreover, the APs treatment modulated lipid metabolism by up-regulating the transcription of associated hepatic genes including PPARα, while down-regulating the transcription of SCAP and its downstream genes associated with lipid synthesis in the liver. Histological assessment showed that the APs treatment also reduced the macrophage infiltration in the aortic root plaque and the inflammatory cells infiltrations to the liver tissues. Moreover, we confirmed that the APs treatment greatly reduced the ox-LDL-induced endothelial dysfunction and monocyte adhesion to rat aortic endothelial cells (RAECs). Mechanistically, the APs treatment suppressed the ROS/MAPK/NF-κB signaling pathway, and consequently, reduced CCL-2, ICAM-1 and VCAM-1 expression. Our results suggest that the APs are a beneficial nutritional supplement for the attenuation of atherosclerosis.
authors: Department of Geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China. xuzherong@yeah.net.
authors: Zhe-Rong
authors: ZR
authors: Xu
authors: Department of Geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China. 20918253@zju.edu.cn.
authors: Jin-You
authors: JY
authors: Li
authors: Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, China. dxw826@zju.edu.cn.
authors: Xin-Wei
authors: XW
authors: Dong
authors: Department of Geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China. yuanyuan17110@163.com.
authors: Zhong-Ju
authors: ZJ
authors: Tan
authors: Department of Geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China. yiyeqiu@126.com.
authors: Wei-Zhen
authors: WZ
authors: Wu
authors: Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, China. dxw826@zju.edu.cn.|Animal Laboratoy Center of Zhejiang University, Hangzhou 310058, China. dxw826@zju.edu.cn.
authors: Qiang-Min
authors: QM
authors: Xie
authors: Department of Geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China. Yangyunmei2008@sina.com.
authors: Yun-Mei
authors: YM
authors: Yang
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000517:prevention & control*; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018932:Chemokine CCL2 / Q000097:blood / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005234:Fatty Liver / Q000517:prevention & control*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000235:genetics; D008077:Lipoproteins, LDL / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D027845:Malus / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D059808:Polyphenols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood / Q000235:genetics; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D018932:Chemokine CCL2; D018799:Intercellular Adhesion Molecule-1; D008077:Lipoproteins, LDL; D008315:Malondialdehyde; D020928:Mitogen-Activated Protein Kinases; D016328:NF-kappa B; D059808:Polyphenols; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C491768:Ccl2 protein, mouse; C099252:oxidized low density lipoprotein
keywords: ApoE−/−mice; apple polyphenols; atherosclerosis; atorvastatin; hepatic steatosis; oxidative stress; vascular Inflammation; western-type diet