Palmitate-induced endothelial dysfunction is attenuated by cyanidin-3-O-glucoside through modulation of Nrf2/Bach1 and NF-κB pathways

Free fatty acids (FFA), commonly elevated in diabetes and obesity, have been shown to impair endothelial functions and cause oxidative stress, inflammation, and insulin resistance. Anthocyanins represent one of the most important and interesting classes of flavonoids and seem to play a role in preventing cardiovascular diseases. Herein, we investigated the in vitro protective effects of cyanidin-3-O-glucoside (C3G) on cell signaling pathways in human umbilical vein endothelial cells (HUVECs) exposed to palmitic acid (PA), the most prevalent saturated FFA in circulation. Our data reported a significant augmentation of free radicals and oxidative stress in HUVECs exposed to PA for 3h, while C3G pretreatment improved intracellular redox status altered by FFA. Moreover, C3G significantly inhibited NF-κB proinflammatory pathway and adhesion molecules induced by PA, and these effects were attributed to the activation of Nrf2/EpRE pathway. In fact, C3G induced Nrf2 nuclear localization and activation of cellular antioxidant and cytoprotective genes at baseline and after PA exposure in endothelial cells. Our data confirm the hypothesis that natural Nrf2 inducers, such as C3G, might be a potential therapeutic strategy to protect vascular system against various stressors preventing several pathological conditions

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 caspase‑3 and p21Waf/Cif1. The results of the current study demonstrated that the ACN extract markedly decreased Caco‑2 cell proliferation, induced apoptosis by activating caspase‑3 cleavage, and upregulated cyclin‑dependent kinase inhibitor 1 (p21Waf/Cif1) expression in a dose dependent manner. Furthermore, ACN extract was able to produce a dose‑dependent increase of intracellular reactive oxygen species (ROS) in Caco‑2 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 Caco‑2 cells by promoting ROS accumulation, inducing caspase‑3 activation, and upregulating the expression of p21Waf/Cif1

Cyanidin-3-O-glucoside modulates intracellular redox status and prevents HIF-1 stabilization in endothelial cells in vitro exposed to chronic hypoxia

The term hypoxia refers to conditions characterized by a relative restriction of oxygen supply. It is usually associated to a paradoxical overproduction of reactive oxygen species (ROS) and to the activation of several transcription factors, including HIF-1α, which in turn trigger angiogenic and apoptotic response. In this study we have investigated the mechanisms by which the anthocyanin Cyanidin-3-O-glucoside (C3G) modulates hypoxia induced response in human endothelial cells (HUVECs). In fact, hypoxia induces an increase of ROS generation in HUVECs paralleled by a loss of antioxidant cellular capacity. According to the observed increase of HO-1 mRNA expression, pretreatment of C3G to HUVEC reduces the entity of oxidative stress thanks to the activation of cellular antioxidant response. C3G also attenuates HIF-1α protein accumulation conditions supporting the hypothesis of a major role of oxidative stress in the presence of low oxygen. Furthermore, the increased expression of angiogenesis and apoptosis markers (MMP-2 and caspase-3) due to HIF-1α activation by hypoxia, is reduced in C3G pretreated cells. Overall, our data suggest that the modulation of intracellular redox status induced by C3G may be an important protective mechanism against endothelial damage in hypoxic conditions

In vitro antibacterial activity of some aliphatic aldehydes from Olea europaea L.

The 'in vitro' activity of eight long-chain aliphatic aldehydes from olive flavor (hexanal, nonanal, (E)-2-hexenal, (E)-2-eptenal, (E)-2-octenal, (E)-2-nonenal, (E)-2-decenal and (E,E)-2,4-decadienal) against a number of standard and freshly isolated bacterial strains has been evaluated. The saturated aldehydes did not exhibit significant antibacterial activity, while the alpha,beta-unsaturated aldehydes showed a broad antimicrobial spectrum and similar activity against Gram-positive and Gram-negative bacteria. The activity of the aldehydes under investigation seems to depend not only on the presence of the alpha,beta-double bond, but also on the chain length from the enal group and on the strain tested

Cyanidin-3-O-glucoside ameliorates palmitate-induced insulin resistance by modulating IRS-1 phosphorylation and release of endothelial derived vasoactive factors

Increased plasma levels of free fatty acids, including palmitic acid (PA), cause insulin resistance in endothelium characterized by a decreased synthesis of insulin-mediated vasodilator nitric oxide (NO), and by an increased production of the vasoconstrictor protein, endothelin-1. Several in vitro and in vivo studies suggest that anthocyanins, natural phenols commonly present in food and vegetables from Mediterranean Diet, exert significant cardiovascular health-promoting activities. These effects are possibly mediated by a positive regulation of the transcription factor Nrf2 and activation of cellular antioxidant and cytoprotective genes. The present study examined, at a molecular level, the effects of cyanidin-3-O-glucoside (C3G), a widely distributed anthocyanin, on PA-induced endothelial dysfunction and insulin resistance in human umbilical vein endothelial cells (HUVECs). Our results indicate that C3G pretreatment effectively reverses the effects of PA on PI3K/Akt axis, and restores eNOS expression and NO release, altered by PA. We observed that these effects were exerted by changes on the phosphorylation of IRS-1 on specific serine and tyrosine residues modulated by PA through the modulation of JNK and IKK activity. Furthermore, silencing Nrf2 transcripts demonstrated that the protective effects of C3G are directly related to the activation of Nrf2