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.