Effect of N-(p-coumaroyl)serotonin and N-feruloylserotonin, major anti-atherogenic polyphenols in safflower seed, on vasodilation, proliferation and migration of vascular smooth muscle cells

Scope: The objective of this study is to investigate a vascular effect of N-(p-coumaroyl)serotonin (CS) and N-feruloylserotonin (FS), major antioxidative indolic polyphenols in safflower seeds with anti-atherogenic properties, with emphasis on effects on vascular smooth muscle cells (VSMCs). Methods and results: Both CS and FS (each 10 to 100 μM) relaxed rat femoral arteries, which were pre-contracted by 10−5 M phenylephrine or 50 mM KCl, independently of their endothelium. Both CS and FS also concentration-dependently inhibited the increase of cytosolic free Ca2+ concentration ([Ca2+]i) that was induced by KCl or 5-hydroxytryptamine in cultured rat VSMCs. Next, we examined the effects of CS and FS on platelet-derived growth factor (PDGF)-BB-evoked proliferation and migration of the VSMCs. Both CS and FS inhibited PDGF-BB-evoked proliferation and migration of the VSMCs in a concentration-dependent manner. They also inhibited PDGF-BB-induced phosphorylation of PDGF receptor β and ERK1/2, and Ca2+ release from sarcoplasmic reticulum in the VSMCs in a concentration-dependent fashion. Conclusion: These results indicated a possible vascular effect of CS/FS to inhibit the activation of VSMCs by blocking the increase of [Ca2+]i and/or blocking PDGF signaling. These may explain a part of anti-atherogenic mechanism that underlies their ability to improve vascular distensibility and to inhibit aortic hyperplasia.