The Ameliorative Effect of Berberine on Vascular Calcification by Inhibiting Endoplasmic Reticulum Stress

Vascular calcification (VC), which currently cannot be prevented or treated, is an independent risk factor for cardiovascular events. We aimed to investigate the ameliorative effect of berberine on VC via the activation of Akt signaling and inhibition of endoplasmic reticulum stress (ERS). The VC model was induced by high-dose Vitamin D3 in rats and beta-glycerophosphate in primary VSMCs of rat aortas, which were evaluated by Alizarin red staining to determine the calcium content and alkaline phosphatase activity. ERS was determined by the levels of GRP78 and CHOP, whereas that of the Akt signaling pathway was determined by the levels of phosphorylated Akt and GSK3β. VC was significantly ameliorated by berberine treatment both in vivo and in vitro, as well as the inhibition of ERS and the activation of the Akt/GSK3 signaling pathway. In the VSMCs of primary rats, tunicamycin, an ERS activator, blocked the ameliorative effect of berberine on VC and ERS but not the activation of Akt/GSK3. The ameliorative effects of berberine on VC, ERS, and the Akt signaling pathway were all prevented by inhibitor IV. 4-Phenylbutyric acid, an ERS inhibitor, can restore the ameliorative effect of berberine on VC and ERS that was blocked by inhibitor IV. Our results are the first to demonstrate the ameliorative effect of VC that was mediated by the activation of the Akt signaling pathway and inhibition of ERS. These results might provide a new pharmaceutical candidate for the prevention and treatment of VC.