Hyperoside suppresses tumor necrosis factor α-mediated vascular inflammatory responses by downregulating mitogen-activated protein kinases and nuclear factor-κB signaling

Vascular inflammation has been suggested to play a key role in the initiation and progression of atherosclerosis. Hyperoside (HPS) is a plant-derived quercetin 3-D-galactoside reported to have anti-inflammatory, anti-oxidant, anti-cancer, anti-hyperglycemic, anti-coagulant, and cardioprotective activities. However, the effects of HPS on vascular inflammation have not been studied. Therefore, in this study, we investigated the suppressive effect of HPS on tumor necrosis factor-alpha (TNF alpha)-dependent inflammatory responses in MOVAS-1 cells, a murine vascular smooth muscle cell (VSMC) line. HPS did not show any significant cytotoxicity up to 10 mu g/mL over 24 h. TNF alpha challenge of VSMCs significantly increased the mRNA (3-fold) and protein expression (20-fold) of vascular cell adhesion molecule-1 (VCAM-1). However, these increases were abolished in the presence of HPS. Additionally, HPS significantly decreased monocyte adhesion to TNF alpha-stimulated VSMCs in a dose-dependent manner. Further, TNF alpha challenge induced activation of mitogen-activated protein kinases (MAPKs), such as p38 MAPK (38.0 +/- 3.08 fold), JNK (51.6 +/- 2.26 fold), and ERK (14.1 +/- 0.77 fold); expression of nuclear factor-kappa B (NF-kappa B;. 4-fold) and TNF receptor 1 (TNFR1; 2.7 +/- 0.198 fold) were also increased. Notably, the TNF alpha-induced expression of these molecules was also significantly inhibited by the presence of HPS. Given that p38 MAPK, JNK, ERK, NF-kappa B, and TNFR1 all play regulatory roles in the expression of VCAM-1, this study provides insight into the mechanism of action of HPS. In summary, HPS can inhibit TNF alpha-mediated vascular inflammatory responses and has potential as a new anti-atherosclerotic drug.