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

Xu ZR, Li JY, Dong XW, Tan ZJ, Wu WZ, Xie QM, Yang YM - Nutrients (2015)

Bottom Line: 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 Article: PubMed Central - PubMed

Affiliation: Department of Geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China. xuzherong@yeah.net.

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.

No MeSH data available.


Related in: MedlinePlus

APs attenuate adhesion, decrease inflammatory factors and ameliorate oxidant stress in RAECs. A: Representative images of ox-LDL-induced monocyte adhesion to RAECs; B: APs treatment inhibits the ox-LDL-induced monocyte adhesion to RAECs in a concentration-dependent manner; C: CCL2, ICAM-1, and VCAM-1 gene expression in RAECs; D: CCL2, ICAM-1, and VCAM-1 level in RAECs supernatant; E: Activity of SOD in RAECs; F: Representative FACS plot of intracellular reactive oxygen species (ROS) and production in RAECs. The values are presented as the means ± S.E.M., n = 6 per group. # p < 0.05, ## p < 0.01, ### p < 0.001 vs. control group (0 μg/mL). * p < 0.05, ** p < 0.01, *** p < 0.001 vs. ox-LDL alone.
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nutrients-07-05324-f006: APs attenuate adhesion, decrease inflammatory factors and ameliorate oxidant stress in RAECs. A: Representative images of ox-LDL-induced monocyte adhesion to RAECs; B: APs treatment inhibits the ox-LDL-induced monocyte adhesion to RAECs in a concentration-dependent manner; C: CCL2, ICAM-1, and VCAM-1 gene expression in RAECs; D: CCL2, ICAM-1, and VCAM-1 level in RAECs supernatant; E: Activity of SOD in RAECs; F: Representative FACS plot of intracellular reactive oxygen species (ROS) and production in RAECs. The values are presented as the means ± S.E.M., n = 6 per group. # p < 0.05, ## p < 0.01, ### p < 0.001 vs. control group (0 μg/mL). * p < 0.05, ** p < 0.01, *** p < 0.001 vs. ox-LDL alone.

Mentions: We showed that the incubation of the vascular endothelial cell with ox-LDL led to endothelial dysfunction and monocyte adhesion (Figure 6A). Pretreatment with the APs for 1 h prevented the ox-LDL-induced monocyte froms from adhering to the RAECs in a concentration-dependent manner (Figure 6B). Given that the AP treatment caused a robust inhibition of the monocyte adhesion and the production of pro-inflammatory cytokines in mice, we hypothesized that the APs treatment would also be able to suppress chemokine expression and the surface molecules in the endothelial cells. Exposing the RAECs to ox-LDLs significantly increased the mRNA transcription (Figure 6C) and protein secretion (Figure 6D) of ICAM-1, VCAM-1, and CCL2. The APs treatment significantly normalized such the ox-LDLs-induced expression of adhesion molecules and chemokines in the RAECs (Figure 6C,D).


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

Xu ZR, Li JY, Dong XW, Tan ZJ, Wu WZ, Xie QM, Yang YM - Nutrients (2015)

APs attenuate adhesion, decrease inflammatory factors and ameliorate oxidant stress in RAECs. A: Representative images of ox-LDL-induced monocyte adhesion to RAECs; B: APs treatment inhibits the ox-LDL-induced monocyte adhesion to RAECs in a concentration-dependent manner; C: CCL2, ICAM-1, and VCAM-1 gene expression in RAECs; D: CCL2, ICAM-1, and VCAM-1 level in RAECs supernatant; E: Activity of SOD in RAECs; F: Representative FACS plot of intracellular reactive oxygen species (ROS) and production in RAECs. The values are presented as the means ± S.E.M., n = 6 per group. # p < 0.05, ## p < 0.01, ### p < 0.001 vs. control group (0 μg/mL). * p < 0.05, ** p < 0.01, *** p < 0.001 vs. ox-LDL alone.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4555163&req=5

nutrients-07-05324-f006: APs attenuate adhesion, decrease inflammatory factors and ameliorate oxidant stress in RAECs. A: Representative images of ox-LDL-induced monocyte adhesion to RAECs; B: APs treatment inhibits the ox-LDL-induced monocyte adhesion to RAECs in a concentration-dependent manner; C: CCL2, ICAM-1, and VCAM-1 gene expression in RAECs; D: CCL2, ICAM-1, and VCAM-1 level in RAECs supernatant; E: Activity of SOD in RAECs; F: Representative FACS plot of intracellular reactive oxygen species (ROS) and production in RAECs. The values are presented as the means ± S.E.M., n = 6 per group. # p < 0.05, ## p < 0.01, ### p < 0.001 vs. control group (0 μg/mL). * p < 0.05, ** p < 0.01, *** p < 0.001 vs. ox-LDL alone.
Mentions: We showed that the incubation of the vascular endothelial cell with ox-LDL led to endothelial dysfunction and monocyte adhesion (Figure 6A). Pretreatment with the APs for 1 h prevented the ox-LDL-induced monocyte froms from adhering to the RAECs in a concentration-dependent manner (Figure 6B). Given that the AP treatment caused a robust inhibition of the monocyte adhesion and the production of pro-inflammatory cytokines in mice, we hypothesized that the APs treatment would also be able to suppress chemokine expression and the surface molecules in the endothelial cells. Exposing the RAECs to ox-LDLs significantly increased the mRNA transcription (Figure 6C) and protein secretion (Figure 6D) of ICAM-1, VCAM-1, and CCL2. The APs treatment significantly normalized such the ox-LDLs-induced expression of adhesion molecules and chemokines in the RAECs (Figure 6C,D).

Bottom Line: 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 Article: PubMed Central - PubMed

Affiliation: Department of Geriatrics, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China. xuzherong@yeah.net.

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.

No MeSH data available.


Related in: MedlinePlus