mangostin and Diabetic-Angiopathies

Diabetic vascular complications are the leading causes of death and disability in patients with diabetes. Alpha-mangostin has been reported to have anti-diabetic capacity in recent years. Here, we investigated the protective function of alpha-mangostin on endothelium in vitro and in vivo experiments. We also observed that alpha-mangostin improved impaired endothelium-dependent vasodilation (EDV) of diabetic animals while it limited the aSMase/ceramide pathway and up-regulated eNOS/NO pathway in aortas from diabetic mice. Meanwhile, alpha-mangostin inhibited elevated aSMase/ceramide pathway and reversed impaired EDV induced by high glucose in isolated mouse aortas. In addition, alpha-mangostin increased phosphorylation of eNOS and NO production in high glucose-treated aortas. Alpha-mangostin normalized high glucose-induced activation of aSMase/ceramide pathway and improved eNOS/NO pathway in endothelial cells with high glucose. In conclusion, alpha-mangostin regulates eNOS/NO pathway and improves EDV in aortas of diabetic mice through inhibiting aSMase activity and endogenous ceramide accumulation.

Topics: Animals; Aorta; Cells, Cultured; Ceramides; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Endothelial Cells; Endothelium, Vascular; Insulin; Male; Mice; Mice, Inbred C57BL; Nitric Oxide; Nitric Oxide Synthase Type III; Phosphorylation; Reactive Oxygen Species; Signal Transduction; Sphingomyelin Phosphodiesterase; Up-Regulation; Vasodilation; Xanthones