The H2S-Donor Erucin Exhibits Protective Effects against Vascular Inflammation in Human Endothelial and Smooth Muscle Cells

Abstract

Preservation of vascular wall integrity against degenerative processes associated with ageing, fat-rich diet and metabolic diseases is a timely therapeutical challenge. The loss of endothelial function and integrity leads to cardiovascular diseases and multiorgan inflammation. The protective effects of the H2S-donor erucin, an isothiocyanate purified by Eruca sativa Mill. seeds, were evaluated on human endothelial and vascular smooth muscle cells. In particular, erucin actions were evaluated on cell viability, ROS, caspase 3/7, inflammatory markers levels and the endothelial hyperpermeability in an inflammatory model associated with high glucose concentrations (25 mM, HG). Erucin significantly prevented the HG-induced decrease in cell viability as well as the increase in ROS, caspase 3/7 activation, and TNF-α and IL-6 levels. Similarly, erucin suppressed COX-2 and NF-κB upregulation associated with HG exposure. Erucin also caused a significant inhibition of p22phox subunit expression in endothelial cells. In addition, erucin significantly prevented the HG-induced increase in endothelial permeability as also confirmed by the quantification of the specific markers VE-Cadherin and ZO-1. In conclusion, our results assess anti-inflammatory and antioxidant effects by erucin in vascular cells undergoing HG-induced inflammation and this protection parallels the preservation of endothelial barrier properties.

Beneficial Health Effects of Glucosinolates-Derived Isothiocyanates on Cardiovascular and Neurodegenerative Diseases

“…ER reduced systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) by roughly 25% and restored blood pressure to normotensive rats’ levels [ 100 ]. ER preserved the integrity of endothelial wall and stimulated intracellular release of H₂S in HUVECs also [ 101 ]. In the setting of hyperglycemia, ER prevented ROS production, downregulated expression of inflammatory mediators (NF-κB, NADPH oxidase p22phox, COX-2, TNF-α and IL-6), inhibited caspase 3/7 activation, averted endothelial hyperpermeability, and preserved endothelial tight junction function (increases expression of vascular endothelial-cadherin (VE-Cadherin) and zonula occludens-1 (ZO-1) proteins, which are cell-cell contact proteins) [ 101 ].…”

“…ER preserved the integrity of endothelial wall and stimulated intracellular release of H₂S in HUVECs also [ 101 ]. In the setting of hyperglycemia, ER prevented ROS production, downregulated expression of inflammatory mediators (NF-κB, NADPH oxidase p22phox, COX-2, TNF-α and IL-6), inhibited caspase 3/7 activation, averted endothelial hyperpermeability, and preserved endothelial tight junction function (increases expression of vascular endothelial-cadherin (VE-Cadherin) and zonula occludens-1 (ZO-1) proteins, which are cell-cell contact proteins) [ 101 ]. E. sativa extract also showed antiplatelet and antithrombotic activities: It inhibited activation of NF-κB p65 in platelets and the expression of P-selectin, thromboxane B2, CCL5 (chemokine(C-C motif) ligand 5), transforming growth factor beta (TGF-β) and IL-1β that contributed to suppression of platelet aggregation and reduction in arterial thrombus formation [ 195 ].…”

“…Studies highlighted have revealed stimulation of MAPK/Nrf2 pathway and inhibition of NF-κB pathway by ER and/or E. sativa [ 190 , 192 ]. Those effects explain ER’s role in maintaining endothelial integrity [ 101 ]. ER suppressed lipid accumulation, weight gain, obesity, and stabilized biochemical features of DM [ 99 ].…”

“…ER preserved myocardial viability and shielded the myocardium from toxicity [ 102 ]. Like other ITCs, the pharmacological effect of ER has been linked to H₂S release, which may explain protection of endothelial integrity and reduction of SBP by ER [ 100 , 101 ].…”

Effect of Microgravity on Endothelial Cell Function, Angiogenesis, and Vessel Remodeling During Wound Healing

“…seeds. Its endothelial positive outcomes are correlated to increased H 2 S intracellular levels ( Martelli et al, 2021 ). Studies are needed to further validate these findings in experimental models and in the clinic and to define other nutraceuticals with protective effects on ECs and promoting reparative angiogenesis.…”