Erucin, a natural isothiocyanate, exerts pro-angiogenic properties in cultured endothelial cells and reverts angiogenic impairment induced by high glucose

Phytother Res. 2024 Jun;38(6):2641-2655. doi: 10.1002/ptr.8183. Epub 2024 Mar 15.

Abstract

Insufficient vessel maintenance adversely impacts patients in terms of tissue reperfusion following stroke or myocardial infarction, as well as during wound healing. Angiogenesis impairment is a feature typical of metabolic disorders acting at the cardiovascular level, such as diabetes. Therapeutic angiogenesis regulation offers promising clinical implications, and natural compounds as pro-angiogenic nutraceuticals hold valuable applications in regenerative medicine. By using cultured endothelial cells from human umbilical veins (HUVEC) we studied functional and molecular responses following exposure to erucin, a natural isothiocyanate derived from Brassicaceae plants and extracted from the seeds of rocket. Erucin (at nanomolar concentrations) promotes cell migration and tube formation, similar to vascular endothelial growth factor (VEGF), through mobilizing paxillin at endothelial edges. At the molecular level, erucin induces signaling pathways typical of angiogenesis activation, namely Ras, PI3K/AKT, and ERK1/2, leading to VEGF expression and triggering its autocrine production, as pharmacological inhibition of soluble VEGF and VEGFR2 dampens endothelial functions. Furthermore, erucin, alone and together with VEGF, preserves endothelial angiogenic functions under pathological conditions, such as those induced in HUVEC by high glucose (HG) exposure. Erucin emerges as a compelling candidate for therapeutic revascularization applications, showcasing promising prospects for natural compounds in regenerative medicine, particularly in addressing angiogenesis-related disorders.

Keywords: angiogenesis; endothelial cells; endothelial dysfunction; erucin; hyperglicemia; isothiocyanate.

MeSH terms

  • Angiogenesis Inducing Agents / pharmacology
  • Brassicaceae / chemistry
  • Cell Movement* / drug effects
  • Glucose*
  • Human Umbilical Vein Endothelial Cells* / drug effects
  • Humans
  • Isothiocyanates* / pharmacology
  • Neovascularization, Physiologic / drug effects
  • Paxillin / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects
  • Sulfides
  • Thiocyanates
  • Vascular Endothelial Growth Factor A* / metabolism
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Glucose
  • Vascular Endothelial Growth Factor A
  • Isothiocyanates
  • erucin
  • Paxillin
  • Angiogenesis Inducing Agents
  • Vascular Endothelial Growth Factor Receptor-2
  • PXN protein, human
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • VEGFA protein, human
  • KDR protein, human
  • Sulfides
  • Thiocyanates