α-Mangostin protects against high-glucose induced apoptosis of human umbilical vein endothelial cells.

Diabetic vascular complications result from high-glucose induced vascular endothelial cell dysfunction. There is an emerging need for novel drugs with vascular endothelial cell protective effects for the treatment of diabetic vascular complications. The present study aimed to investigate the protective effect of α-mangostin against high-glucose induced apoptosis of cultured human umbilical vein endothelial cells (HUVECs). HUVECs were treated with glucose to induce apoptosis. The expression of the apoptosis-related proteins, Bcl-2, Bax, and cleaved caspase-3, were detected by Western blotting. Ceramide concentration and acid sphingomyelinase (ASM) activity were assayed by HPLC. The cell apoptosis rate was detected by flow cytometry after staining with annexin V/propidium iodide (PI). Compared with HUVECs cultured in 5 mM glucose, cells cultured in 30 mM glucose exhibited a higher apoptosis rate, up-regulation of cleaved caspase-3 and Bax (proapoptotic proteins), down-regulation of Bcl-2 (anti-apoptotic protein), increased ceramide concentration, and enhanced ASM activity (all P<0.05). α-Mangostin (15 µM) significantly attenuated the high-glucose induced increase in apoptosis rate (8.64 ± 2.16 compared with 19.6 ± 3.54%), up-regulation of cleaved caspase-3 and Bax, down-regulation of Bcl-2, elevation of ceramide level, and enhancement of ASM activity (all P<0.05). The effects of desipramine were similar to those of α-mangostin. The protective effect of α-mangostin on high-glucose induced apoptotic damage may be mediated by an inhibition of ASM and thus a decreased level of ceramide.