Sulforaphane, a naturally occurring
isothiocyanate present in cruciferous vegetables, has received wide attention for its potential to improve vascular function in vitro. However, its effect in vivo and the molecular mechanism of
sulforaphane at physiological concentrations remain unclear. Here, we report that a
sulforaphane concentration as low as 0.5 μM significantly inhibited
tumor necrosis factor-α (TNF-α)-induced adhesion of monocytes to human umbilical vein endothelial cells, a key event in the pathogenesis of
atherosclerosis both in static and under flow conditions. Such physiological concentrations of
sulforaphane also significantly suppressed TNF-α-induced production of
monocyte chemotactic protein-1 and adhesion molecules including soluble vascular adhesion molecule-1 and soluble
E-selectin, key mediators in the regulation of enhanced endothelial cell-monocyte interaction. Furthermore,
sulforaphane inhibited TNF-α-induced nuclear factor (NF)-κB transcriptional activity, Inhibitor of NF-κB alpha (IκBα) degradation and subsequent NF-κB p65 nuclear translocation in endothelial cells, suggesting that
sulforaphane can inhibit
inflammation by suppressing NF-κB signaling. In an animal study,
sulforaphane (300 ppm) in a mouse diet significantly abolished TNF-α-increased ex vivo monocyte adhesion and circulating adhesion molecules and
chemokines in C57BL/6 mice. Histology showed that
sulforaphane treatment significantly prevented the eruption of endothelial lining in the intima layer of the aorta and preserved
elastin fibers' delicate organization, as shown by Verhoeff-van Gieson staining. Immunohistochemistry studies showed that
sulforaphane treatment also reduced vascular adhesion molecule-1 and monocyte-derived F4/80-positive macrophages in the aorta of TNF-α-treated mice. In conclusion,
sulforaphane at physiological concentrations protects against TNF-α-induced vascular endothelial
inflammation, in both in vitro and in vivo models. This anti-inflammatory effect of
sulforaphane may be, at least in part, associated with interfering with the NF-κB pathway.