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

Mol Nutr Food Res. 2011 Oct;55(10):1561-71. doi: 10.1002/mnfr.201000545. Epub 2011 Jun 6.


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 Ca(2+) concentration ([Ca(2+) ](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 Ca(2+) 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 [Ca(2+) ](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.

MeSH terms

  • Animals
  • Arteries / drug effects
  • Becaplermin
  • Calcium / metabolism
  • Carthamus tinctorius / chemistry
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • In Vitro Techniques
  • Male
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / metabolism
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Phosphorylation
  • Potassium Chloride / pharmacology
  • Proto-Oncogene Proteins c-sis / pharmacology
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Platelet-Derived Growth Factor beta / metabolism
  • Sarcoplasmic Reticulum / drug effects
  • Sarcoplasmic Reticulum / metabolism
  • Seeds / chemistry
  • Serotonin / analogs & derivatives*
  • Serotonin / pharmacology
  • Vasodilation / drug effects*


  • Proto-Oncogene Proteins c-sis
  • Becaplermin
  • N-feruloylserotonin
  • Serotonin
  • Potassium Chloride
  • Receptor, Platelet-Derived Growth Factor beta
  • Mitogen-Activated Protein Kinase 3
  • N-(p-coumaroyl)serotonin
  • Calcium