The pathophysiology of
cardiovascular diseases is complex and may involve oxidative stress-related pathways.
Eriodictyol is a
flavonoid present in citrus fruits that demonstrates anti-inflammatory, anti-
cancer, neurotrophic, and
antioxidant effects in a range of pathophysiological conditions including
vascular diseases. Because oxidative stress plays a key role in the pathogenesis of
cardiovascular disease, the present study was designed to verify whether
eriodictyol has therapeutic potential. Upregulation of
heme oxygenase-1 (HO-1), a phase II detoxifying
enzyme, in endothelial cells is considered to be helpful in
cardiovascular disease. In this study, human umbilical vein endothelial cells (HUVECs) treated with
eriodictyol showed the upregulation of HO-1 through extracellular-regulated
kinase (ERK)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathways. Further,
eriodictyol treatment provided protection against
hydrogen peroxide-provoked cell death. This protective effect was eliminated by treatment with a specific inhibitor of HO-1 and RNA interference-mediated knockdown of HO-1 expression. These data demonstrate that
eriodictyol induces ERK/Nrf2/ARE-mediated HO-1 upregulation in human endothelial cells, which is directly associated with its vascular protection against oxidative stress-related endothelial injury, and propose that targeting the upregulation of HO-1 is a promising approach for therapeutic intervention in
cardiovascular disease.