Abstract 474: Combined Polyphenols Synergistically Inhibit Tumor Necrosis Factor-alpha-Induced Monocytes Adhesion to Human Endothelial Cells

Abstract

Monocyte recruitment and adhesion to the endothelium is a crucial step the development of endothelial dysfunction and therefore induces cardiovascular disease (CVD), the number one killer of Americans. Emerging evidence shows that polyphenols, the secondary plant metabolites present in a large variety of foods, have the potential ability in reducing risk of CVD. The aims of this study are to investigate the synergistic anti-inflammatory effects of combined polyphenols at physiological levels and define relevant molecular mechanisms. Our results indicate that resveratrol, curcumin and luteolin dose-dependently inhibited tumor necrosis factor-alpha (TNF-α)-induced monocytes adhesion to human endothelial cells. The half maximal effective concentration (EC50) values of curcumin, luteolin and resveratrol are 15 μM, 8 μM and 26 μM respectively. Particularly, combined luteolin (4μM) and curcumin (8 μM) or combination of curcumin (8 μM) and resveratrol (13 μM) synergistically inhibited TNF-α-induced monocytes adhesion to endothelial cells while the individual chemicals did not have such effect at the physiological concentrations. The combination index(CI)value of curcumin plus luteolin and curcumin plus resveratrol at the selected concentrations are 0.7 and 0.82, respectively, indicating these two combinations have synergistic anti-inflammatory effects. We also found that these phytochemicals ameliorated the TNF-α-enhanced protein expressions of vascular cell adhesion molecule 1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1), two major indicators of vascular inflammation in endothelial cells. These data suggest that these combined polyphenols maybe a novel strategy to diminish vascular inflammation and therefore prevent/treat cardiovascular disease.