Ultrasound-assisted extraction of anthocyanins and total phenolic compounds in Vitis vinifera L. 'Tempranillo' winemaking lees

Winemaking lees (WL) are the less exploited by-products from the winemaking industry. This by-product is generated after the fermentation of grape must and its composition is variable, although it is mainly made up of lysed yeasts, tartaric acid, colloids, polyphenols and ashes. Of all the compounds that can be found in lees, polyphenols exhibit particularly powerful bioactive properties and their extraction for their reuse in different matrices could be a matter of particular interest.Ultrasound-assisted extraction (UAE) has been used to extract both total anthocyanins (TA) and total phenolic compounds (TPC) from lees from Vitis vinifera L. 'Tempranillo' vinification. The optimization of six extraction variables (% methanol, pH, temperature, amplitude, cycle and ratio solvent:mass) was performed using a Box-Behnken design (BBD) where TA and TPC were considered independent variables. The UAE method that has been developed in this research could be a new rapid and efficient method to extract TPC and, coupled to chromatographic methodologies, identify up to fourteen different anthocyanins from WL. The objective of this study is to determine WL polyphenolic content and its potential for further uses in other procedures aiming to create value from vinification waste

Evaluation of the agronomic performance of 'Syrah' and 'Tempranillo' when grafted on 12 rootstocks

Beyond pest resistance, rootstocks significantly influence the performance of grapevine varieties. However, the effect of the rootstock is strongly affected by its interaction with the environment, and it is therefore necessary to evaluate their influence in a particular terroir. With the aim of evaluating the influence of 12 rootstocks on the agronomic performance of 'Syrah' and 'Tempranillo', a trial was established in 2011 and 2012 in Miranda de Arga (Navarra, Spain), under the typical environmental conditions of the Ebro Valley. Growth and yield, as well as industrial and phenolic maturity parameters were analysed during four consecutive seasons (2015-2018). Most rootstocks showed a similar performance with both varieties, not always following the trends reported in bibliography, which highlights the relevance of studying rootstocks in different conditions. 3309 C was the rootstock conferring the highest vigour, whereas the lowest were provided by 420 A MGt and 'Fercal'. The implications on grape composition were much more diverse, and were partially conditioned by yield. Results were obtained during the four first harvests of the vineyard, and could therefore change to some extent as the vineyard reaches stability

Derivatives of grindelic acid: from a non-active natural diterpene to synthetic antitumor derivatives

Using several reactions that include homologations and asymmetric epoxidations as well as Ugi and Huisgen couplings, we generated a small focused library of new derivatives from the labdane-type diterpene grindelic acid. These compounds were evaluated as cytotoxic agents against a panel of five human solid tumor cell lines (HBL-100, HeLa, SW1573, T-47D, and WiDr). The presence of the diamide functionalizations enhanced the cytotoxic effect. N-benzyl-N-(1-(benzylamino)-2-methyl-1-oxopropan-2-yl)grindelicamide, proved to be the most active product in all cell lines tested, with values of 0.95 (± 0.38) μM against HBL-100 cells.Fil: Reta, Guillermo Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto de Investigaciones En Tecnología Química; ArgentinaFil: Chiaramello, Alejandra Ilda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto de Investigaciones en Tecnología Química; ArgentinaFil: García, Celina. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "Antonio Gonzalez"; EspañaFil: León, Leticia G.. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "Antonio Gonzalez"; EspañaFil: Martín, Victor S.. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "Antonio Gonzalez"; EspañaFil: Padrón, José M.. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-orgánica "Antonio Gonzalez"; EspañaFil: Tonn, Carlos Eugenio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto de Investigaciones En Tecnología Química; ArgentinaFil: Donadel, Osvaldo Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto de Investigaciones En Tecnología Química; Argentin

The Protective Effect of a Unique Mix of Polyphenols and Micronutrients against Neurodegeneration Induced by an In Vitro Model of Parkinson’s Disease

: Parkinson's disease (PD) is second-most common disabling neurological disorder worldwide, and unfortunately, there is not yet a definitive way to prevent it. Polyphenols have been widely shown protective efficacy against various PD symptoms. However, data on their effect on physio-pathological mechanisms underlying this disease are still lacking. In the present work, we evaluated the activity of a mixture of polyphenols and micronutrients, named A5+, in the murine neuroblastoma cell line N1E115 treated with 6-Hydroxydopamine (6-OHDA), an established neurotoxic stimulus used to induce an in vitro PD model. We demonstrate that a pretreatment of these cells with A5+ causes significant reduction of inflammation, resulting in a decrease in pro-inflammatory cytokines (IFN-γ, IL-6, TNF-α, and CXCL1), a reduction in ROS production and activation of extracellular signal-regulated kinases (ERK)1/2, and a decrease in apoptotic mechanisms with the related increase in cell viability. Intriguingly, A5+ treatment promoted cellular differentiation into dopaminergic neurons, as evident by the enhancement in the expression of tyrosine hydroxylase, a well-established dopaminergic neuronal marker. Overall, these results demonstrate the synergic and innovative efficacy of A5+ mixture against PD cellular pathological processes, although further studies are needed to clarify the mechanisms underlying its beneficial effect

Risk factors for diabetic foot ulcers: An Albanian retrospective study of inpatients with type 2 diabetes

OBJECTIVE: The aim of this study was to assess the impact of glucose control, diabetes-related complications and cardiometabolic risk factors on the risk of diabetic foot ulcers (DFUs) and DFU complications in Albanian adult inpatients with T2D.PATIENTS AND METHODS: We conducted a retrospective case-control study on 482 Albanian adult inpatients with T2D. DFU was defined as a full-thickness skin lesion requiring >= 14 days for healing and was classified at the time of hospital admission. Demographic and biochemical parameters of the study participants, the presence of comorbidities and diabetes -related complications at the time of hospital admission were evaluated through a retrospective chart review.RESULTS: Mean age of study participants was 54.8 +/- 10.7 years. Participants (284 males and 198 females) were divided into two groups: DFU (cases; n=104) and non-DFU (controls; n=378). Multivariate analysis (performed by a logistic regression model) revealed that the most relevant independent variables associated with DFU were BMI [OR= 0.62; p=0.007], HDL-cholesterol [OR=0.00; p<0.0001], triglycerides [OR=7.48; p=0.0004], cigarette smoking [OR=26.46; p=0.005], duration of diabetes [OR=1.53; p<0.0001], fasting plasma glucose (FPG) [OR=1.06; p<0.0001], systolic blood pressure (SBP) [OR=1.13; p=0.0004] and insulin therapy alone [OR=0.11; p=0.02]. ROC curve analysis showed that FPG (AUC=0.83), glycated hemoglobin (HbA1c) (AUC=0.75), triglycerides (AUC=0.78) and HDL-cholesterol (AUC=0.82) were the most reliable biomarkers able to detect DFU. In the DFU group, the most relevant independent variables associated with previous minor lower-extremity amputations (LEAs) were represented by HbA1c [OR=1.47; p=0.03], age <55 years [OR=0.12; p=0.0 5] and female sex [OR=4.18; p=0.03]; whereas the most relevant independent variables associated with diabetic peripheral neuropathy (DPN) were HbA1c [OR=1.70; p=0.006], SBP [OR=1.08; p=0.05], BMI [OR=1.20; p=0.03] and lack of cigarette smoking [OR=0.07; p=0.01]. Correlation analysis (performed through the nonparametric Spearman's rank correlation test or through the parametric Pearson test, as appropriate) revealed a significant positive relationship between HbA1c and FPG (r=0.58; p<0.0001), ulcer surface area (r=0.50; p<0.0001), ulcer grade (r= 0.23; p=0.02), minor LEAs (r=0.20; p=0.04), DPN (r=0.41; p<0.0001), and metformin therapy alone (r=0.72; p<0.0001). There was a significant inverse correlation between HbA1c and insulin therapy alone (r=-0.31; p=0.01) and combined metformin and insulin therapy (r=-0.60; p<0.0001). Both DFU and non-DFU groups exhibited suboptimal mean LDL-cholesterol levels (>100 mg/dl) and mean HbA1c values >7.5%. Moreover, in DFU group HbA1c values were markedly elevated (>= 10%) particularly in patients with a grade 3 ulcer and an ulcer surface area >= 4 cm2, as well as in patients with history of minor LEAs and in patients affected by DPN.CONCLUSIONS: The present study suggested that longer duration of diabetes, cigarette smoking, lower HDL-cholesterol levels, poor glucose control, and elevated triglyceride and SBP values may all represent major risk factors for the development of DFU in Albanian patients with T2D. Thus, community interventions and health policies aimed to improve the management of diabetes and related cardiometabolic risk factors should be urgently implemented in Albania, in order to prevent DFUs and other diabetes complications in patients with T2D

Polyphenols and ischemic stroke: Insight into one of the best strategies for prevention and treatment

Ischemic stroke (IS) is still among the leading causes of death and disability worldwide. The pathogenic mechanisms beyond its development are several and are complex and this is the main reason why a functional therapy is still missed. The beneficial effects of natural compounds against cardiovascular diseases and IS have been investigated for a long time. In this article, we reviewed the association between the most studied polyphenols and stroke protection in terms of prevention, effect on acute phase, and rehabilitation. We described experimental and epidemiological studies reporting the role of flavonols, phenolic acid, and stilbens on ischemic mechanisms leading to stroke. We analyzed the principal animal models used to evaluate the impact of these micronutrients to cerebral blood flow and to molecular pathways involved in oxidative stress and inflammation modulation, such as sirtuins. We reported the most significant clinical trials demonstrated as the persistent use of polyphenols is clinically relevant in terms of the reduction of vascular risk factors for IS, such as Atrial Fibrillation. Interestingly, different kinds of polyphenols provide brain protection by activating different pathways and mechanisms, like inducing antithrombotic effect, such as Honokiol. For this reason, we discussed an appropriate integrative use of them as a possible therapeutic alternative against stroke

Novel therapeutic approaches based on the pathological role of gut dysbiosis on the link between nonalcoholic fatty liver disease and insulin resistance

The growing global epidemic of obesity and type 2 diabetes mellitus has de-termined an increased prevalence of NAFLD (non-alcoholic fatty liver disease), making it the most common chronic liver disease in the West-ern world and a leading cause of liver transplan-tation. In the last few years, a rising number of studies conducted both on animal and human models have shown the existence of a close as-sociation between insulin resistance (IR), dys-biosis, and steatosis. However, all the mecha-nisms that lead to impaired permeability, inflam- mation, and fibrosis have not been fully clari- fied. Recently, new possible treatment modali- ties have received much attention. To reach the review purpose, a broad-ranging literature search on multidisciplinary research databases was performed using the following terms alone or in combination: "NAFLD", "gut dysbiosis", "insulin resistance", "inflammation", "probiotics", "Chinese herbs". The use of probiotics, prebiotics, symbiotics, postbiotics, fecal microbiota transplant (FMT), Chinese herbal medicine, antibiotics, diet (poly -phenols and fasting diets), and minor therapies such as carbon nanoparticles, the MCJ protein, water rich in molecular hydrogen, seems to be able to improve the phenotypic pattern in NA-FLD patients. In this review, we provide an overview of how IR and dysbiosis contribute to the development and progression of NAFLD, as well as the thera-peutic strategies currently in use

A Novel Mix of Polyphenols and Micronutrients Reduces Adipogenesis and Promotes White Adipose Tissue Browning via UCP1 Expression and AMPK Activation

Background: Obesity is a pandemic disease characterized by excessive severe body comorbidities. Reduction in fat accumulation represents a mechanism of prevention, and the replacement of white adipose tissue (WAT) with brown adipose tissue (BAT) has been proposed as one promising strategy against obesity. In the present study, we sought to investigate the ability of a natural mixture of polyphenols and micronutrients (A5(+)) to counteract white adipogenesis by promoting WAT browning. Methods: For this study, we employed a murine 3T3-L1 fibroblast cell line treated with A5(+), or DMSO as control, during the differentiation in mature adipocytes for 10 days. Cell cycle analysis was performed using propidium iodide staining and cytofluorimetric analysis. Intracellular lipid contents were detected by Oil Red O staining. Inflammation Array, along with qRT-PCR and Western Blot analyses, served to measure the expression of the analyzed markers, such as pro-inflammatory cytokines. Results: A5(+) administration significantly reduced lipids' accumulation in adipocytes when compared to control cells (p < 0.005). Similarly, A5(+) inhibited cellular proliferation during the mitotic clonal expansion (MCE), the most relevant stage in adipocytes differentiation (p < 0.0001). We also found that A5(+) significantly reduced the release of pro-inflammatory cytokines, such as IL-6 and Leptin (p < 0.005), and promoted fat browning and fatty acid oxidation through increasing expression levels of genes related to BAT, such as UCP1 (p < 0.05). This thermogenic process is mediated via AMPK-ATGL pathway activation. Conclusion: Overall, these results demonstrated that the synergistic effect of compounds contained in A5(+) may be able to counteract adipogenesis and then obesity by inducing fat browning

Sildenafil Reduces Insulin-Resistance in Human Endothelial Cells

The efficacy of Phosphodiesterase 5 (PDE5) inhibitors to re-establish endothelial function is reduced in diabetic patients. Recent evidences suggest that therapy with PDE5 inhibitors, i.e. sildenafil, may increase the expression of nitric oxide synthase (NOS) proteins in the heart and cardiomyocytes. In this study we analyzed the effect of sildenafil on endothelial cells in insulin resistance conditions in vitro