Abstract
d-Fagomine, an analogue of 1-deoxynojirimycin (DNJ), has been shown to have hypoglycemic activity. This study is aimed at investigating if d-fagomine could attenuate high glucose-induced oxidative stress in human umbilical vein endothelial cells (HUVECs) and elucidate the underlying mechanism. Our results showed that d-fagomine reduced intracellular reactive oxygen species (ROS) production and malondialdehyde (MDA) levels. It also reversed the decrease of superoxide dismutases (SOD) and glutathione reductase (GR) activity, suggesting an inhibitory effect of d-fagomine on oxidative damage in HUVECs. d-Fagomine restored the loss of mitochondrial membrane potential, implying its protective role on mitochondrial function. In addition, d-fagomine activated the AMPK signaling pathway through LKB1, increased the expression of SIRT1 and PGC-1α, and attenuated the inhibitory effect on SIRT1 and PGC-1α activity caused by AMPK and SIRT1 inhibitor. d-Fagomine attenuated high glucose-induced oxidative stress in HUVECs through the AMPK/SIRT1/PGC-1α pathway.