Grape seed proanthocyanidin extracts inhibit vascular cell adhesion molecule expression induced by advanced glycation end products through activation of peroxisome proliferators-activated receptor gamma.
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.
Ma
Li
L
Department of Geriatrics, Qilu Hospital of Shandong University, Jinan, China.
Gao
Hai-qing
HQ
Li
Bao-ying
BY
Ma
Ya-bing
YB
You
Bei-an
BA
Zhang
Feng-lei
FL
D000704:Analysis of Variance; D015153:Blotting, Western; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D017127:Glycation End Products, Advanced / Q000378:metabolism / Q000494:pharmacology*; D056604:Grape Seed Extract; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D047495:PPAR gamma / Q000096:biosynthesis* / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D044945:Proanthocyanidins / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000187:drug effects*; D014841:von Willebrand Factor / Q000187:drug effects
D017127:Glycation End Products, Advanced; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D018836:Inflammation Mediators; D047495:PPAR gamma; D010936:Plant Extracts; D044945:Proanthocyanidins; D019010:Vascular Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D012710:Serum Albumin, Bovine