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

Aim of the study: 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. Materials and methods: 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). Results: HUVEC incubated with 100 mu g/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 mu M 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 mu g/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. Conclusions: 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. (C) 2010 Elsevier Ireland Ltd. All rights reserved.