Cyanidin-3-Galactoside Attenuates Glycated LDL-Induced Monocyte Adhesion and Endoplasmic Reticulum Stress in Vascular Endothelial Cells

Abstract

Background: Anthocyanins are potent phyto-antioxidants with cardioprotective effects. Cyanidin-3-galactoside (C3Ga) is a common type of anthocyanin in dark skin fruits, but its effects on vascular inflammation remains unclear. Purpose: The present study aims to examine the effects of C3Ga on monocyte adhesion to endothelial cells (EC) and relevant cellular mechanism. Methods: Monocyte adhesion was assessed by incubation of THP-1 human monocytes with human umbilical vein EC exposed to glycated low density lipoprotein (gLDL). Inflammatory, fibrinolytic and endoplasmic reticulum (ER) stress related mediators in EC were analyzed using Western blotting or immunoassays. Results: C3Ga dose-dependently inhibited gLDL-induced monocyte adhesion to EC. C3Ga reduced gLDL-induced increases in the intensity of plasminogen activator inhibitor-1, urokinase plasminogen activator (uPA), uPA receptor, LDL receptor-like protein , intracellular cell adhesion molecule-1, monocyte chemotactic protein-1, tumor necrosis factor-α, toll-like receptor-4, and myeloid differentiation primary response gene-88 and attenuated that of thioflavin T fluorescent intensity, a biomarker of ER stress, in EC. The inhibitory effects of C3Ga on monocyte adhesion, inflammatory mediators and ER stress were substantially weaker than cyanidin-3-glucoside, but comparable to that of delphinidin-3-glucoside. Conclusion: The results suggest that C3Ga or plant products enriched with C3Ga are potential nutraceutical or functional food for suppressing vascular inflammation and ER stress under diabetic condition. Key words: Cyanidin-3-galactoside; monocyte adhesion; endothelial cells; inflammatory and fibrinolytic mediators; endoplasmic reticulum stress.