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

Author:

Genah Shirley12ORCID,Ciccone Valerio2,Filippelli Arianna2,Simonis Vittoria2,Martelli Alma3ORCID,Piragine Eugenia3,Pagnotta Eleonora4ORCID,Pecchioni Nicola5,Calderone Vincenzo3,Morbidelli Lucia2

Affiliation:

1. Department of Pediatric Hematology and Oncology, Bambino Gesù Children's Hospital IRCCS Rome Italy

2. Department of Life Sciences University of Siena Siena Italy

3. Department of Pharmacy University of Pisa Pisa Italy

4. Research Centre for Cereal and Industrial Crops CREA Bologna Italy

5. Research Centre for Cereal and Industrial Crops CREA Foggia Italy

Abstract

AbstractInsufficient 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.

Publisher

Wiley

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