Grape Seed Proanthocyanidin Extracts Inhibit Vascular Cell Adhesion Molecule Expression Induced by Advanced Glycation End Products Through Activation of Peroxisome Proliferators-Activated Receptor γ

Abstract

Although evidence has shown that grape seed proanthocyanidin extracts (GSPE) can selectively inhibit cell adhesion molecule expression induced by advanced glycation end products (AGEs), the underlying molecular mechanism has not been extensively characterized. To study the antiinflammation mechanism of GSPE, we investigated the effect of GSPE on Von Willebrand factor (vWF) content and the expression of vascular cell adhesion molecule-1 (VCAM-1) induced by AGEs and the effect of GSPE on peroxisome proliferators-activated receptor gamma (PPAR gamma) and receptor for AGEs (RAGE) expression in human umbilical vein endothelial cells (HUVEC). HUVEC were preincubated with or without GSPE of different concentrations (10 mg/L, 50 mg/L, and 100 mg/L) for 4 hours before being treated with 200 mg/L AGEs or unmodified bovine serum albumin (BSA) for 24 hours. The expression of RAGE and PPAR gamma was investigated by Western blot. VCAM-1 expression was measured by flow cytometry and vWF content by enzyme-linked immunosorbent assay (ELISA). Results showed that GSPE significantly inhibited the expression of VCAM-1 in HUVEC and reduced the content of vWF in culture fluid induced by AGEs in a dose-dependent manner. AGEs activated the expression of RAGE and inhibited PPAR gamma expression in HUVEC, whereas GSPE inhibited the expression of RAGE through activation of PPAR gamma in HUVEC simultaneously. These findings indicated that GSPE inhibited the cell inflammatory factor expression and protected the function of endothelial cell through activation of PPAR gamma expression and inhibition of RAGE expression.

Effects of Grape Seed Proanthocyanidin Extracts on Aortic Pulse Wave Velocity in Streptozocin Induced Diabetic Rats

“…It has been reported that GSPEs have antioxidant properties, as evidenced by the increase in pancreatic glutathione and reduction of lipid peroxidation, so it might have improved the function of cells in the diabetic rat, and influenced insulin effects by acting directly on specific components of the insulinsignaling transduction pathway. 19,37) GSPEs reduced aortic wall stiffness in the diabetic rats, with no change in wall stress. This observation is in line with the hypothesis that AGE-induced cross-linking of scleroproteins in adult animals increases the aortic EM.…”

“…[15][16][17] Our previous experiments showed that GSPEs displayed anti-nonenzymatic glycation and anti-inflammation, reducing receptor of advanced glycation end product (RAGE) protein expression, leading to decreased expression of high level vascular cell adhesion molecule 1 induced by advanced glycation end products (AGEs) in endothelial cells. 18,19) In our present study, we examined the effects of AGEs on the diabetic aorta and evaluated the efficacy of aortic protection by GSPEs. Moreover, aortic function was assessed by measurement of aortic PWV, EM, and * Xiao-li Li and Bao-ying Li contributed equally to this work.…”

Relaxin Enhances S100A4 and Promotes Growth of Human Thyroid Carcinoma Cell Xenografts

“…The transmembrane receptor receptor for advanced glycation endproducts was shown to be the receptor for S100 proteins (54)(55)(56), potentially including S100A4 (55)(56)(57). Receptor for advanced glycation endproducts protein is expressed in HUVEC cells (58,59), implicating secreted S100A4 as a new paracrine executioner of RLN2 actions in thyroid carcinoma angiogenesis.…”

Grape Seed Nutraceuticals for Disease Prevention: Current Status and Future Prospects

“…It was reported that procyanidins inhibited platelet aggregation [40] and had also successfully inhibited the oxidation of low-density lipoprotein (LDL) as well as contributed to reduction in risks of heart disease associated with atherosclerosis [41]. In addition, procyanidins performed very well as anti-inlammatory [42,43], antimutagens [44], anticancer [45][46][47], and antiviral [48] agents.…”