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.

Dietary apple polyphenols supplementation enhances antioxidant capacity and improves lipid metabolism in weaned piglets

“…In this study, our results showed that APPs significantly increased the mRNA expressions of hepatic CAT , GST and SOD1 mRNA levels in weaned piglets. Our data also showed that the serum MDA content of weaned piglets was significantly decreased by APPs, which was consistent with the results in rodents (Ogino et al, ; Xu et al, ). Together, the results above suggested that dietary APPs supplementation enhanced antioxidative status in liver and serum.…”

“…We found that dietary APPs supplementation had no effect on growth performance, which is consistent with previous reports (Manzano et al, ; Nakazato et al, ; Yoshida et al, ). On the contrary, some other investigations based on mouse model of hyperlipidaemia or rats fed cholesterol showed different response patterns (improvement or decrease in growth performance; Osada et al, ; Xu et al, ). The reason might be the discrepancies in the experimental animal or energy level of diets.…”

Fiber and phenolic compounds contribution to the hepatoprotective effects of mango diets in rats fed high cholesterol/sodium cholate

“…Similar activations have been reported in response to apple pomace (Sharma et al, ) and green tea (Na & Surh, ) consumption, as well as from other fruits and vegetables (Orena et al, ). Nonetheless, activation of other signaling pathways could have been involved, such as mitogen activated protein kinases (Beltrán‐Debón et al, ; Xu et al, ) to ameliorate adipose inflammation and dysfunction of hepatocytes during NASH development.…”

Fibrinopeptide A Induces Expression of C-Reactive Protein via the ROS-ERK1/2/ P38-NF-κB Signal Pathway in Vascular Smooth Muscle Cells

“…The existed evidence certifies that MAPK may activate NF-κB [44]. NF-κB activation regulates the generation of mediators resulting in the thrombotic potential of human atherosclerotic plaques, such as tissue factor, matrix metalloproteinases and inflammatory cytokines [45].…”