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Apple Polyphenols Decrease Atherosclerosis and Hepatic Steatosis in ApoE−/− Mice through the ROS/MAPK/NF-κB Pathway

1
Department of Geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China
2
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, China
3
Animal Laboratoy Center of Zhejiang University, Hangzhou 310058, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Nutrients 2015, 7(8), 7085-7105; https://doi.org/10.3390/nu7085324
Received: 16 July 2015 / Revised: 7 August 2015 / Accepted: 13 August 2015 / Published: 24 August 2015
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. View Full-Text
Keywords: apple polyphenols; western-type diet; atherosclerosis; hepatic steatosis; atorvastatin; oxidative stress; vascular Inflammation; ApoE−/−mice apple polyphenols; western-type diet; atherosclerosis; hepatic steatosis; atorvastatin; oxidative stress; vascular Inflammation; ApoE−/−mice
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Xu, Z.-R.; Li, J.-Y.; Dong, X.-W.; Tan, Z.-J.; Wu, W.-Z.; Xie, Q.-M.; Yang, Y.-M. Apple Polyphenols Decrease Atherosclerosis and Hepatic Steatosis in ApoE−/− Mice through the ROS/MAPK/NF-κB Pathway. Nutrients 2015, 7, 7085-7105.

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