Caffeic acid protects the endothelium from high glucose-induced dysfunction through Nrf2 and HO-1 activation

Recent studies suggest that Caffeic acid (CA), a dietary hydroxycinnamic acid abundant in coffee, exerts antioxidant activity and it is known to have antidiabetic effect in streptozotocin-induced diabetic rats. Oxidative stress, due to the high glucose (HG) concentrations, plays a pivotal role in the progress of diabetic impediments and in micro- and macrovascular complications. Previous studies have shown that HG induces nuclear factor-κB (NF-κB), a redox-sensitive transcription factors involved in the activation of endothelial inflammatory dysfunction. Herein we investigated if physiological concentrations of CA (10 nM) were able to protect human endothelial cells (HUVECs) against alterations induced by HG. In particular we examined the effects of CA on intracellular redox status biomarkers such as glutathione, superoxide and Total Antioxidant Status, and the modulation of NF-κB pathway. Furtheremore, in order to understand the molecular mechanisms underlying the protective effects exerted by CA, we evaluated the involvement of nuclear factor erythoid 2- related factor (Nrf2) that is able to upregulates the expression of antioxidant genes. At this aim HUVECs were exposed to HG 25 mM, to miminc diabetic condition, in presence or not of CA. The results show the ability of CA to inhibit HG-induced nuclear translocation of NF-κB and its downstream gene E-selectin. Moreover CA restores antioxidant level in HUVECs exposed to HG by upregulating Nrf2 pathway. Taken together, the present data suggested that CA could suppress HG-induced inflammatory process, which may be closely related with the inhibition of oxidative stress. Our findings may highlight a new therapeutic intervention for the prevention of vascular diseases.