Low nanomolar caffeic acid attenuates high glucose-induced endothelial dysfunction in primary human umbilical-vein endothelial cells by affecting NF-κB and Nrf2 pathways.

Hyperglycemia contributes to dysregulate endothelial function associated with diabetes, leading to initiation and propagation of vascular complications and dysfunction. Caffeic acid (CA), a dietary hydroxycinnamic acid abundant in coffee, has been reported to exert antidiabetic effects in rat models. Herein, we investigated the molecular effects of physiological concentrations of CA (10 nM) against endothelial dysfunction induced by high glucose (HG) in human endothelial cells (HUVECs). HUVECs were exposed to HG 25 mM, to mimic diabetic condition, in presence of CA. Intracellular redox status (reduced glutathione, superoxide dismutase (SOD) and total antioxidant activity levels), and NF-κB pathway were examined. We also evaluated the involvement of NF-E2-related factor 2 (Nrf2)/electrophile responsive element (EpRE) pathway. Our data show that CA inhibits HG-induced nuclear translocation of NF-κB and the downstream expression of endothelial adhesion molecule 1 and restores antioxidant levels by upregulating Nrf2/EpRE pathway. Our data suggest that CA can suppress several aspects of HG-induced endothelial dysfunction through the modulation of intracellular redox status controlled by the transcription factor Nrf2. These findings highlight that low physiological concentration of CA achievable specifically upon food consumption are able to prevent endothelial dysfunction associated with inflammation and oxidative stress induced by high concentration of glucose. © 2016 BioFactors, 43(1):54-62, 2017.

Berry anthocyanins reduce proliferation of human colorectal carcinoma cells by inducing caspase-3 activation and p21 upregulation.

Colorectal cancer is the fourth most common type of cancer worldwide, and adenocarcinoma cells that form the majority of colorectal tumors are markedly resistant to antineoplastic agents. Epidemiological studies have demonstrated that consumption of fruits and vegetables that are rich in polyphenols, is linked to reduced risk of colorectal cancer. In the present study, the effect of a standardized anthocyanin (ACN)­rich extract on proliferation, apoptosis and cell cycle in the Caco-2 human colorectal cancer cell line was evaluated by trypan blue and clonogenic assays and western blot analysis of cleaved caspase­3 and p21Waf/Cif1. The results of the current study demonstrated that the ACN extract markedly decreased Caco­2 cell proliferation, induced apoptosis by activating caspase­3 cleavage, and upregulated cyclin­dependent kinase inhibitor 1 (p21Waf/Cif1) expression in a dose dependent manner. Furthermore, ACN extract was able to produce a dose­dependent increase of intracellular reactive oxygen species (ROS) in Caco­2 cells, together with a light increase of the cell total antioxidant status. In conclusion, the present study demonstrated that a standardized berry anthocyanin rich extract inhibited proliferation of Caco­2 cells by promoting ROS accumulation, inducing caspase­3 activation, and upregulating the expression of p21Waf/Cif1.