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The antihypertensive effect of the soluble fraction of wine lees (WL) from Cabernet variety grapes was recently reported by our group. This blood pressure (BP)-lowering effect was attributed to the presence of flavanols and anthocyanins. In this context, phenolic-enriched wine lees (PWL) could potentially exhibit a stronger bioactivity. Therefore, the aim of this study was to obtain a soluble fraction of WL with increased phenolic content and evaluate its functionality. The PWL were obtained using an enzyme-assisted extraction based on the hydrolysis of WL proteins with Flavourzyme®. They contained 57.20% more total phenolic compounds than WL, with anthocyanins and flavanols being the largest families present. In addition, PWL also showed greater angiotensin-converting enzyme inhibitory and antioxidant activities. Finally, the antihypertensive activity of the PWL was evaluated in spontaneously hypertensive rats. A single dose of 5 mL/kg body weight of PWL showed a greater BP-lowering effect than the one shown by WL. Moreover, this antihypertensive effect was more prolonged than the one produced by the antihypertensive drug Captopril. These results demonstrate that enzymatic protein hydrolysis is a useful method to maximize the extraction of phenolic compounds from WL and to obtain extracts with enhanced functionalities. View Full-Text

The use of a single family of dietary bioactive compounds has not been sufficient to manage highly regulated mechanisms such as body weight. Therefore, we aimed to evaluate the effect of a multifunctional ingredient (MIX) based on the co-administration of a low dose of conjugated linoleic acid with the protein hydrolysate from chicken feet, Hpp11, and a mixture of grape-seed proanthocyanidins and berry anthocyanins on body weight management in obese rats fed a cafeteria diet. The daily oral administration of the MIX for three weeks significantly reversed obesity and hyperleptinemia and increased energy expenditure and fat oxidation. In addition, animals administered the MIX exhibited greater hypothalamic activation of STAT3 in POMC-expressing neurons than non-supplemented animals. Our results strongly suggest that the co-administration of different bioactive compounds could be a promising strategy to complement the existing therapies against obesity and leptin resistance.

DOI: 10.1038/srep24977, Proanthocyanidins (PACs) have been reported to modulate multiple targets by simultaneously controlling many pivotal metabolic pathways in the liver. However, the precise mechanism of PAC action on the regulation of the genes that control hepatic metabolism remains to be clarified. Accordingly, we used a metabolomic approach combining both nuclear magnetic resonance and mass spectrometry analysis to evaluate the changes induced by different doses of grape-seed PACs in the liver of healthy rats. Here, we report that PACs significantly increased the hepatic nicotinamide adenine dinucleotide (NAD+) content in a dose-dependent manner by specifically modulating the hepatic concentrations of the major NAD+ precursors as well as the mRNA levels of the genes that encode the enzymes involved in the cellular metabolism of NAD+. Notably, Sirtuin 1 (Sirt1) gene expression was also significantly up-regulated in a dose-response pattern. The increase in both the NAD+ availability and Sirt1 mRNA levels, in turn, resulted in the hepatic activation of SIRT1, which was significantly associated with improved protection against hepatic triglyceride accumulation. Our data clearly indicates that PAC consumption could be a valid tool to enhance hepatic SIRT1 activity through the modulation of NAD+ levels.

DOI: 10.1016/j.ijcard.2016.04.184, Background/objectives The mechanisms underlying aortic dilation in bicuspid aortic valve (BAV) disease are unknown. Circulating endothelial microparticles (EMPs) have emerged as biomarkers of endothelial damage. We sought to evaluate the relationships among EMPs, BAV disease, and aortic dilation. Methods Four evaluations were used. Circulating EMPs (PECAM+, E-selectin+) were compared between BAV patients and tricuspid aortic valve (TAV) control subjects. The variables related to circulating EMPs were investigated in BAV patients. Circulating EMP levels were compared between BAV and TAV patients with a dilated aorta. Finally, circulating EMPs in BAV patients were evaluated over time with respect to aortic valve surgery (AVS) or aortic surgery. Results We observed higher levels of circulating PECAM+ EMPs in the BAV patients than in the control subjects (3.98 ± 0.2 vs. 2.39 ± 0.4 per log PECAM+ EMPs/μl, p = 0.001). Aortic dilation was the most significant variable that correlated with the PECAM+ EMP levels in the BAV patients (β = 0.321, p = 0.008). The BAV patients with aortic dilation exhibited higher PECAM+ EMP levels than the TAV patients with dilated aortas, and this correlation was independent of aortic valve function. We observed a drastic decrease in the circulating PECAM+ EMPs following AVS and aortic root replacement (4.27 ± 0.6 and 1.75 ± 0.3 per log PECAM+ EMPs/μl, p = 0.002). Conclusion The observed pattern of higher circulating PECAM+ EMP levels links BAV disease to endothelial damage and aortic dilation. Circulating PECAM+ EMPs were identified as a biological variable related to aortic dilation in patients with BAV disease.

DOI: 10.1038/srep24977, Proanthocyanidins (PACs) have been reported to modulate multiple targets by simultaneously controlling many pivotal metabolic pathways in the liver. However, the precise mechanism of PAC action on the regulation of the genes that control hepatic metabolism remains to be clarified. Accordingly, we used a metabolomic approach combining both nuclear magnetic resonance and mass spectrometry analysis to evaluate the changes induced by different doses of grape-seed PACs in the liver of healthy rats. Here, we report that PACs significantly increased the hepatic nicotinamide adenine dinucleotide (NAD+) content in a dose-dependent manner by specifically modulating the hepatic concentrations of the major NAD+ precursors as well as the mRNA levels of the genes that encode the enzymes involved in the cellular metabolism of NAD+. Notably, Sirtuin 1 (Sirt1) gene expression was also significantly up-regulated in a dose-response pattern. The increase in both the NAD+ availability and Sirt1 mRNA levels, in turn, resulted in the hepatic activation of SIRT1, which was significantly associated with improved protection against hepatic triglyceride accumulation. Our data clearly indicates that PAC consumption could be a valid tool to enhance hepatic SIRT1 activity through the modulation of NAD+ levels.