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

Xiao-ming LI,Qing-zhu WANG,Lei GUO

(Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,Department of Pharmacolog,School of Basic Medicine,Peking Union Medical College,Beijing 100005,China)

T2-25

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

Xiao-ming LI,Qing-zhu WANG,Lei GUO

(Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,Department of Pharmacolog,School of Basic Medicine,Peking Union Medical College,Beijing 100005,China)

OBJECTIVETo investigate the beneficial effect of berberine(BBR)on atherosclerosis in 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).METHODS48 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 or solvent 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-glycerophos⁃phate in SMC cells and the effect of BBR on the content of calcium was examined.RESULTS4-week berberine treatment markedly lowered serum TC and LDL-c levels and improved the plaquestabilityin Apo-/-E mice fed with a high-fat diet(P＜0.05 or P＜0.01)which was comparable with the effect of atorvastatin.Berberine also 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.CONCLUSIONBBR 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.

berberine;atherosclerosis;vascular endothelium;inflammation;vascular calcification

The project supported by National Natural Science Foundation of China(81402943);CAMS Major Collaborative Innovation Project(2016-I2M-1-011);and PUMC Youth Fund(3332015168）

Lei GUO,Tel:18601067653,E-mail：leiguo@ibms.cams.cn