Grape seed proanthocyanidin extracts prevent hyperglycemia-induced monocyte adhesion to aortic endothelial cells and ameliorates vascular inflammation in high-carbohydrate/high-fat diet and streptozotocin-induced diabetic rats.

ABSTRACT

The role of grape seed proanthocyanidin extracts (GSPE) in the prevention of diabetic vascular inflammation and monocyte-endothelial cell interactions has not been examined. We used high-carbohydrate/high-fat diet and streptozotocin to induce diabetes and treated with GSPE (125, 250 and 500 mg/kg) for 24 weeks. Inflammatory response and intima-media thickness (IMT) in aortic root were observed by hematoxylin-eosin (H&E) staining. The receptor of advanced glycation end products (RAGE) expression of aortic root was assayed by immunohistochemistry. Isolation of rat aortic endothelial cell (RAEC) was used to ex vivo monocyte adhesion assay. In this study, inflammatory response and IMT were significantly increased in diabetic rats compared to non-diabetic rats, which can be reversed by GSPE (p < 0.05). Advanced glycation end products (AGEs) and RAGE in diabetic rats were significantly higher than in non-diabetic animals, but were effectively lowered by 500 mg/kg GSPE for 24 weeks (p < 0.05). There was a greater binding of WEHI 78/24 cells to RAEC isolated from diabetic rats as compared with normal rats, which can be normalized by GSPE. The concentrations of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in RAEC cell supernatant and serum of diabetic rats were greater than those in the normal rats. This study provided evidence that GSPE may be an effective agent to protect vasculature from diabetes-caused inflammation and endothelial dysfunction.