Large-leaf yellow tea attenuates high glucose-induced vascular endothelial cell injury by up-regulating autophagy and down-regulating oxidative stress

Vascular endothelial cell injury induced by high glucose (HG) plays an important role in the occurrence and development of diabetic vascular complications. Yellow tea has a protective effect on vascular endothelial cells. However, the molecular mechanisms underlying this effect are unclear. In this study, the effects of the n -butanol fraction of Huoshan large-leaf yellow tea extract (HLYTBE) on vascular endothelial injury were investigated using human umbilical vein endothelial cells (HUVECs) and diabetic mice. In HUVECs, HLYTBE significantly reduced the production of reactive oxygen species, increased the activity of anti-oxidases (superoxide dismutase and glutathione peroxidase), enhanced the production of reduced glutathione, and decreased the level of oxidized glutathione, thereby improving cell viability. HLYTBE also promoted autophagosome formation, increased the LC3-II/LC3-I ratio, increased the expressions of Beclin1 and Atg 5, and decreased the expression of p62. HLYTBE up-regulated p -AMPK and down regulated p -mTOR, and these effects were reversed by compound C, an AMPK inhibitor. HLYTBE reduced apoptosis and cytochrome C expression, and these effects were attenuated by the autophagy inhibitor 3-methyladenine. In vivo studies showed that HLYTBE improved the impaired pyruvate tolerance, glucose tolerance, and insulin resistance; reduced the concentrations of blood glucose, glycated serum protein, lipids, and 8-isomeric prostaglandin 2α; increased the anti-oxidase activity in serum; and alleviated pathological damage in the thoracic aorta of diabetic mice induced by high sucrose-high fat diet along with streptozotocin. The results suggest that HLYTBE protects the vascular endothelium by up-regulating autophagy via the AMPK/mTOR pathway and inhibiting oxidative stress. HLYTBE protects HUVECs against HG-induced injury via AMPK/mTOR-regulated autophagy and inhibiting oxidative stress. Moreover, HLYTBE improves glucose and lipid metabolism, exhibits antioxidant activity and reduces arterial vascular injury in vivo .