Crocin Protects Human Umbilical Vein Endothelial Cells from High Glucose-Induced Injury Via Inhibiting the Endoplasmic Reticulum Stress Response

Background: Endothelial dysfunction plays a key role in diabetic atherosclerosis. High glucose (HG) is considered a stimulator in the development of diabetic atherosclerosis. The endoplasmic reticulum (ER) stress response is involved in HG-induced vascular injury. Crocin has antioxidative and antiapoptotic properties. Objective: The current study was to evaluate whether crocin can protect human umbilical vein endothelial cells (HUVECs) from HG-induced injury and explored the associated mechanism. Methods: HUVECs were treated with 33 mmol/L glucose as the HG condition. The endothelial protective effects of crocin were evaluated by comparison with the control groups. Results: The exposure of HUVECs to HG for 24 h remarkably induced the ER stress response and a sequence of injuries, as demonstrated an increase in the apoptotic cell number, the reactive oxygen species level and inflammatory cytokine generation, as well as a decline in vascular endothelial growth factor A expression. These changes were markedly alleviated by pretreating the HUVECs with either crocin or 4-phenylbutyrate (ER stress inhibitor) before exposure to HG. Conclusion: Crocin exerted antioxidative, antiapoptotic, anti-inflammatory and proangiogenic effects in the HG-induced HUVEC injury model, which were probably mediated by a favorable modification of ER stress that requires further investigation.