Effects of physical exercise associated with a diet enriched with natural antioxidants on cerebral hypoperfusion and reperfusion injury in spontaneously hypertensive rats.

Oxidative stress is implicated in the pathogenesis of arterial hypertension. The reduction in the bioavailability of nitric oxide (NO) causes endothelial dysfunction, altering the functions of cerebral blood vessels. Physical exercise and intake of antioxidants improve the redox state, increasing the vascular NO production and/or the decrease in NO scavenging by reactive oxygen species (ROS). The present study was aimed at assessing the effects of physical exercise associated with a diet enriched with antioxidants from the Annurca apple in preventing the microvascular damage due to cerebral hypoperfusion and reperfusion injury in spontaneously hypertensive rats (SHRs). The rat pial microcirculation was investigated by intravital fluorescence microscopy through a parietal closed cranial window. As expected, SHRs subjected to physical exercise or an antioxidants-enriched diet showed a reduction of microvascular permeability, ROS formation, and leukocyte adhesion to venular walls, with a major effect of the antioxidants-enriched diet, when compared to untreated SHRs. Moreover, capillary perfusion was preserved by both treatments in comparison with untreated SHRs. Unexpectedly, the combined treatments did not induce higher effects than the single treatment. In conclusion, our results support the efficacy of physical activity or antioxidant supplement in reducing the microvascular alterations due to hypertension and ascribe to an antioxidants-enriched diet effective microvascular protection in SHRs.

Post-Bariatric Hypoglycemia Is Associated with Endothelial Dysfunction and Increased Oxidative Stress.

Post-bariatric hypoglycemia (PBH) is a potentially serious complication that may occur after bariatric surgery. Recurrent hypoglycemia may exert detrimental effects on vascular function. The aim of the present study was to evaluate endothelial function and oxygen reactive compounds in patients who experience PBH compared with controls. We performed a cross-sectional study on subjects with PBH (HYPO) and those without (NO-HYPO), detected by seven-day continuous glucose monitoring (CGM) performed at least twelve months after bariatric surgery. We enrolled 28 post-bariatric subjects (17.9% males, mean age 40.6 ± 10.7 years), with 18 in the HYPO group and 10 in the NO-HYPO group. In the two groups, we measured brachial artery flow-mediated dilation (FMD), oxidized low-density lipoproteins (oxLDL) and reactive oxygen metabolites (D-ROMs). The HYPO group had significantly lower FMD values than the NO-HYPO group (3.8% ± 3.0 vs. 10.5% ± 2.0, p < 0.001). A significant correlation was found between FMD and the time spent in hypoglycemia (rho = −0.648, p < 0.001), the number of hypoglycemic events (rho = −0.664, p < 0.001) and the mean glucose nadir (rho = 0.532, p = 0.004). The HYPO group showed significantly higher levels of D-ROMs (416.2 ± 88.7 UCARR vs. 305.5 ± 56.3 UCARR, p < 0.001) and oxLDLs (770.5 ± 49.7 µEq/L vs. 725.1 ± 51.6 µEq/L, p = 0.035) compared to the NO-HYPO group. In the multiple linear regression analysis, hypoglycemia independently predicted FMD values (ß = −0.781, p < 0.001), D-ROMs (ß = 0.548, p = 0.023) and oxLDL levels (ß = 0.409, p = 0.031). PBH is associated with impaired endothelial function accompanied by increased oxidative stress.

The Pomace Extract Taurisolo Protects Rat Brain From Ischemia-Reperfusion Injury.

Taurisolo® is a pomace extract from Aglianico Grapes, a wine cultivar native to Campania (Southern Italy). It exhibits a very high polyphenolic content and, consumed as a nutraceutical, is effective in reducing the level of Trimethylamine N-oxide (TMAO), a cardiovascular disease risk factor marker. We here show the effects of Taurisolo® on rat brain microvascular alterations induced by a diminution in cerebral blood flow (CBFD) for 30 min, due to bilateral common carotid artery occlusion, and subsequent blood flow restoration (CBFR) for 60 min. The rat pial microcirculation was investigated by intravital fluorescence microscopy through a parietal closed window implanted into the skull bone. The rat pial arterioles were classified according to Strahler's ordering scheme, from smaller penetrating arterioles up to the larger ones. Western blotting analysis and mass spectrometry (MS)-based metabolomics were used to investigate the expression of endothelial nitric oxide synthase (eNOS) or the presence of peroxidized cardiolipin and several inflammatory mediators, respectively. Radical Oxygen Species (ROS) formation and neuronal loss were assessed. In rats CBFD and CBFR caused a decrease in arteriolar diameter, increase in fluorescent leakage and in adhesion of leukocytes to venular walls, reduction in the length of perfused capillaries and increment of ROS formation with large infarct size. Taurisolo®, intravenously or orally administered, induced pial arteriolar dilation (up to >30% of baseline), prevented fluorescent leakage, adhesion of leukocytes, ROS formation, while facilitated capillary perfusion and significantly reduced infarct size. These effects were accompanied by an increase in eNOS expression. Mass-spectrometry metabolomics analysis detected a marked decrease in the amount of peroxidized cardiolipin and pronounced reduction in pro-inflammatory prostaglandins and thromboxane Txb2. Altogether, these results extend the nutraceutical potential of Taurisolo® and suggest their eligibility for preventing brain damage due to ischemia-reperfusion injury.

Annurca Apple Polyphenols Ignite Keratin Production in Hair Follicles by Inhibiting the Pentose Phosphate Pathway and Amino Acid Oxidation.

Patterned hair loss (PHL) affects around 50% of the adult population worldwide. The negative impact that this condition exerts on people's life quality has boosted the appearance of over-the-counter products endowed with hair-promoting activity. Nutraceuticals enriched in polyphenols have been recently shown to promote hair growth and counteract PHL. Malus pumila Miller cv. Annurca is an apple native to Southern Italy presenting one of the highest contents of Procyanidin B2. We have recently shown that oral consumption of Annurca polyphenolic extracts (AAE) stimulates hair growth, hair number, hair weight and keratin content in healthy human subjects. Despite its activity, the analysis of the molecular mechanism behind its hair promoting effect is still partially unclear. In this work we performed an unprecedented metabolite analysis of hair follicles (HFs) in mice topically treated with AAE. The metabolomic profile, based on a high-resolution mass spectrometry approach, revealed that AAE re-programs murine HF metabolism. AAE acts by inhibiting several NADPH dependent reactions. Glutaminolysis, pentose phosphate pathway, glutathione, citrulline and nucleotide synthesis are all halted in vivo by the treatment of HFs with AAE. On the contrary, mitochondrial respiration, ß-oxidation and keratin production are stimulated by the treatment with AAE. The metabolic shift induced by AAE spares amino acids from being oxidized, ultimately keeping them available for keratin biosynthesis.

Annurca apple (M. pumila Miller cv Annurca) extracts act against stress and ageing in S. cerevisiae yeast cells.

BACKGROUND: During the past years, a number of studies have demonstrated the positive effect of apple on ageing and different diseases such as cancer, degenerative and cardiovascular diseases. The unicellular yeast Saccharomyces cerevisiae represents a simple eukaryotic model to study the effects of different compounds on lifespan. We previously demonstrated that apple extracts have anti-ageing effects in this organism because of their antioxidant properties. In particular, the effect is related to the presence in this fruit of polyphenols, which give a large contribution to the antioxidant activity of apples. METHODS: We we used a clonogenic assay to assess the viability and the resistance to oxidative stress of S. cerevisiae cells in the presence of Annurca apple extracts. The production of ROS and the aberrant morphology of nuclei were detected by cell staining with the fluorescent dies Dihydrorhodamine 123 and DAPI, respectively. Mitochondrial morphology was analyzed by following the localization of the mito-GFP protein into the mitochondrial matrix. RESULTS: In this study, we show that apple extracts can increase yeast lifespan, reduce the levels of reactive oxygen species and cell sensitivity to oxidative stress, and prevent nuclei and mitochondria fragmentation protecting cells from regulated cell death. CONCLUSIONS: In this paper, by using the yeast S. cerevisiae as a model, we have demonstrated that Annurca extracts possess antioxidant properties thanks to which the extracts can reduce the intracellular ROS levels and have anti-apoptotic functions thus prolonging cell lifespan. These results contribute to knowledge on the effects of natural compounds on ageing and support the use of yeast as a model organism for the development of simple tests to assess the effectiveness of bioactive substances from natural sources.