Beneficial effect of berberine on atherosclerosis based on attenuating vascular inflammation and cal

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OBJECTIVE To investigate the beneficial effect of berberine(BBR)on atherosclerosisin Apo~(-/-) E mice and explore the underlying mechanisms based on attenuating vascular inflammation and modulating calcification in human umbilical vein endothelial cells(HUVECs) and smooth muscle cells(SMCs).METHODS 48 Apo-/-E mice,at 6-8 weeks old,were randomly allocated into 4 groups:normal,model,bbr and atorvastatin(positive control) groups with 12 mice in each group.They were fed with high-fat diet for 4 weeks except those in Normal group and then treated with indicated drugs orsolvent for another 4 weeks.The morphology and inflammation infiltration of aortic were examined with HE staining.The expression of BMP-2 in aortic was examined by immumohistochemical staining.Blood lipid levels were examined by automatic biochemical analyzer.The expression of IL-6,TNF-α and BMP-2 in serum and tissues was detected by ELISA method.The expression of ALP and the content of calcium were detected by commercially-available kits.HUVEC cells were stimulated with TNF-α and incubated with various concentrations of BBR for 24 h.The contents of intercellular cell adhesion molecule-1(ICAM-1),vascular cell adhesion molecule(VCAM-1),matrix metalloprotein-9(MMP-9) in the culture supernatant were detected by ELISA method.Calcification was induced with β-glycerophosphatein SMC cells and the effect of BBR on the content of calcium was examined.RESULTS 4-week berberine treatment markedly lowered serum TC and LDL-c levels and improved the plaque stability in Apo-/-E mice fed with a high-fat diet(P<0.05 or P<0.01) which was comparable with the effect of atorvastatin.Berberineal so significantly decreased the levels of IL-6 and TNF-α in mice serum and aortic tissues(P<0.05 or P<0.001).Berberine tended to decrease ALP,BMP-2 levels and the content of calcium in mice serum and aortic tissues(P<0.05,P<0.01 or P<0.001) which were not observed in atorvastatin group.Berberine significantly lowered the levels of ICAM-1,VCAM-1,and MMP-9 in TNF-α-stimulated HUVECs.It can also lowered the content of calcium in SMCs.CONCLUSION BBR can profitably regulate the levels of blood lipid in mice fed with a high-fat diet,decrease the injury caused by inflammation,and attenuate vascular calcification.It may improve atherosclerosis and play a role in cardiovascular protection. OBJECTIVE To investigate the beneficial effect of berberine (BBR) on atherosclerosisin Apo ~ (- / -) E mice and explore the underlying mechanisms based on attenuating vascular inflammation and modulating calcification in human umbilical vein endothelial cells (HUVECs) and smooth muscle cells ) .METHODS 48 Apo - / - E mice, at 6-8 weeks old, were randomly assigned into 4 groups: normal, model, bbr and atorvastatin (positive control) groups with 12 mice in each group. The were were with high- fat diet for 4 weeks except those in Normal group and then treated with indicated drugs orsolvent for another 4 weeks. The morphology and inflammation infiltration of aortic were examined with HE staining. The expression of BMP-2 in aortic was examined by immumohistochemical staining. Blood lipid levels were examined by automatic biochemical analyzer. The expression of IL-6, TNF-α and BMP-2 in serum and tissues was detected by ELISA method. The expression of ALP and the content of calcium were detected by commercial- available kits. HUVEC cells were stimulated with TNF-α and incubated with various concentrations of BBR for 24 h. The contents of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM- 9 (MMP-9) in the culture supernatant were detected by ELISA method. Calcification was induced with β-glycerophosphate in SMC cells and the effect of BBR on the content of calcium was examined .RESULTS 4-week berberine treatment markedly lowered serum TC and LDL -c levels and improved the plaque stability in Apo - / - E mice fed with a high-fat diet (P <0.05 or P <0.01) which was comparable with the effect of atorvastatin. Berberineal so significantly decreased the levels of IL-6 (P <0.05 or P <0.001) .Berberine tended to decrease ALP, BMP-2 levels and the content of calcium in mice serum and aortic tissues P <0.001) which were not observed in atorvastatin group. Berberine significantly lowered the levels of ICA M-1,VCAM-1, and MMP-9 in TNF-α-stimulated HUVECs.It can also reduce the content of calcium in SMCs.CONCLUSION BBR can profitably regulate the levels of blood lipid in mice fed with a high-fat diet, decrease the injury caused by inflammation, and attenuate vascular calcification. It may improve atherosclerosis and play a role in cardiovascular protection.
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