Abstract
Berberine (BBR), a Chinese medicine extracted from natural plant, has been demonstrated to improve lipid disorders. Oxidized low-density lipoprotein (oxLDL), a proatherogenic lipoprotein, has been shown to be involved in vascular endothelial cell dysfunction such as excessive or abnormal proliferation. The purpose of the present study was to investigate the impacts of BBR on cell proliferations as well as potential involving signal pathways. HUVECs were stimulated with oxLDL and co-cultured with BBR at a variety of concentrations in different time points. The data showed that oxLDL (10-100 μg/ml) remarkably promoted human umbilical vein endothelial cells (HUVECs) proliferation assessed by Cell Counting Kit-8 (CCK-8) and EdU assay. The effects were found to be involved in up-regulation of proliferating cell nuclear antigen (PCNA), nuclear factor кB (NF-кB) and oxidized low density lipoprotein receptor 1 (LOX-1) and activation of phosphatidylinositol 3 kinase (PI3K)/Akt, ERK1/2 and p38 mitogen-activated protein kinase (MAPK) signaling pathways evaluated by either real time polymerase chain reaction (PCR) or western blot analysis. Interestingly, HUVECs proliferation was significantly inhibited by BBR (5-25 μg/ml), which down-regulated the expression of PCNA, NF-кB and LOX-1 and reduced the phosphorylation of Akt, ERK1/2 and p38MAPK. Furthermore, the anti-proliferative effect of BBR on HUVECs was effectively abrogated by a PI3K inhibitor LY294002, an ERK1/2 inhibitor PD98059 and a p38 inhibitor SB202190 partly through the restoration of phosphorylation of Akt, ERK1/2 and p38MAPK. Taken together, our data suggested that BBR inhibited ox-LDL-induced HUVECs proliferation by decreasing the expression of PCNA, NF-кB and LOX-1 and suppressing the activation of PI3K/Akt, ERK1/2 and p38MAPK pathways, indicating a latent candidate for anti-atherosclerosis clinically.