Preventive effects of chebulic acid isolated from Terminalia chebula on advanced glycation endproduct-induced endothelial cell dysfunction

The aqueous extract of Terminalia chebular fruits was reported to have anti-hyperglycemia and anti-diabetic complication effects. The present study therefore investigated the protective mechanism of chebulic acid, a phenolcarboxylic acid compound isolated from the ripe fruits of Terminalia chebula against advanced glycation endproducts (AGEs)-induced endothelial cell dysfunction. To investigate the protective mechanism of chebulic acid against vascular endothelial dysfunction human umbilical vein endothelial cells (HUVEC) were treated with chebulic acid in the presence/absence of glyceraldehyde-related AGEs (glycer-AGEs). HUVEC incubated with 100 μg/ml of glycer-AGEs had significantly enhanced reactive oxygen species formation, whereas the treatment of chebulic acid dose-dependently reduced glycer-AGE-induced formation to 108.2 ± 1.9% for 25 μM versus 137.8 ± 1.1% for glycer-AGEs treated alone. The transendothelial electrical resistance (TER) value of the glycer-AGEs group was dramatically decreased to 76.9 ± 2.2% compared to the control, whereas chebulic acid treatment prevented glycer-AGE-induced TER change with a value of 91.3 ± 5.3%. The incubation of confluent HUVEC with 100 μg/ml of glycer-AGEs for 24 h remarkably increased the adhesion of human monocytic THP-1 cells compared to non-stimulated HUVEC. These increases in HUVEC adhesiveness were dose-dependently reduced by chebulic acid. The present study shows the effects of chebulic acid against the progression of AGE-induced endothelial cell dysfunction suggesting that this compound may constitute a promising intervention agent against diabetic vascular complications.