Neuroprotective Effects of Bioavailable Polyphenol-Derived Metabolites against Oxidative Stress-Induced Cytotoxicity in Human Neuroblastoma SH-SY5Y Cells

Oxidative stress is involved in cell death in neurodegenerative diseases. Dietary polyphenols can exert health benefits, but their direct effects on neuronal cells are debatable because most phenolics are metabolized and do not reach the brain as they occur in the dietary sources. Herein, we evaluate the effects of a panel of bioavailable polyphenols and derived metabolites at physiologically relevant conditions against H2O2-induced apoptosis in human neuroblastoma SH-SY5Y cells. Among the 19 metabolites tested, 3,4-dihydroxyphenylpropionic acid, 3,4-dihydroxyphenylacetic acid, gallic acid, ellagic acid, and urolithins prevented neuronal apoptosis via attenuation of ROS levels, increased REDOX activity, and decreased oxidative stress-induced apoptosis by preventing the caspase-3 activation via the mitochondrial apoptotic pathway in SH-SY5Y cells. This suggests that dietary sources containing the polyphenol precursors of these molecules such as cocoa, berries, walnuts, and tea could be potential functional foods to reduce oxidative stress associated with the onset and progress of neurodegenerative diseases.This work was funded by Projects CICYT AGL2011-22447, AGL2015-64124-R (MINECO, Spain), 201370E068 (CSIC, Spain), and BACCHUS (FP7-KBBE-2012-6-single stage, European Commission Grant Agreement 312090). A.G.-S. and M.A.N.-S. are holders of a “Juan de la Cierva” contract and an FPI grant, respectively, from MINECO.Peer reviewe

Dietary Phenolics against Breast Cancer. A Critical Evidence-Based Review and Future Perspectives

© 2020 by the authors.Breast cancer (BC) is the most common malignancy and the leading cause of cancer-related death in adult women worldwide. Over 85% of BC cases are non-hereditary, caused by modifiable extrinsic factors related to lifestyle, including dietary habits, which play a crucial role in cancer prevention. Although many epidemiological and observational studies have inversely correlated the fruit and vegetable consumption with the BC incidence, the involvement of their phenolic content in this correlation remains contradictory. During decades, wrong approaches that did not consider the bioavailability, metabolism, and breast tissue distribution of dietary phenolics persist behind the large currently existing gap between preclinical and clinical research. In the present review, we provide comprehensive preclinical and clinical evidence according to physiologically relevant in vitro and in vivo studies. Some dietary phenolics such as resveratrol (RSV), quercetin, isoflavones, epigallocatechin gallate (EGCG), lignans, and curcumin are gaining attention for their chemopreventive properties in preclinical research. However, the clinical evidence of dietary phenolics as BC chemopreventive compounds is still inconclusive. Therefore, the only way to validate promising preclinical results is to conduct clinical trials in BC patients. In this regard, future perspectives on dietary phenolics and BC research are also critically discussedThis research was funded by the projects PID2019-103914RB-I00 (MICINN, Spain), 19900/GERM/15 (Fundación Séneca de la Región de Murcia, Spain), and 201870E014 and 201770E081 (CSIC, Spain). J.A.G.B. was supported by a Juan de la Cierva contract (IJCI-2016-27633) from the Ministry of Science, Innovation and Universities (Spain) and a Standard European Marie Curie Fellowship from the European Commission. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 838991.Peer reviewe

Grape Resveratrol Increases Serum Adiponectin and Downregulates Inflammatory Genes in Peripheral Blood Mononuclear Cells: A Triple-Blind, Placebo-Controlled, One-Year Clinical Trial in Patients with Stable Coronary Artery Disease

This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.[Purpose] The grape and wine polyphenol resveratrol exerts cardiovascular benefits but evidence from randomized human clinical trials is very limited. We investigated dose-depending effects of a resveratrol-containing grape supplement on stable patients with coronary artery disease (CAD) treated according to currently accepted guidelines for secondary prevention of cardiovascular disease.[Methods] In a triple-blind, randomized, placebo-controlled, one-year follow-up, 3-arm pilot clinical trial, 75 stable-CAD patients received 350 mg/day of placebo, resveratrol-containing grape extract (grape phenolics plus 8 mg resveratrol) or conventional grape extract lacking resveratrol during 6 months, and a double dose for the following 6 months. Changes in circulating inflammatory and fibrinolytic biomarkers were analyzed. Moreover, the transcriptional profiling of inflammatory genes in peripheral blood mononuclear cells (PBMCs) was explored using microarrays and functional gene expression analysis.[Results] After 1 year, in contrast to the placebo and conventional grape extract groups, the resveratrol-containing grape extract group showed an increase of the anti-inflammatory serum adiponectin (9.6 %, p = 0.01) and a decrease of the thrombogenic plasminogen activator inhibitor type 1 (PAI-1) (−18.6 %, p = 0.05). In addition, 6 key inflammation-related transcription factors were predicted to be significantly activated or inhibited, with 27 extracellular-space acting genes involved in inflammation, cell migration and T-cell interaction signals presenting downregulation (p < 0.05) in PBMCs. No adverse effects were detected in relation to the study products.[Conclusions] Chronic daily consumption of a resveratrol-containing grape nutraceutical could exert cardiovascular benefits in stable-CAD patients treated according to current evidence-based standards, by increasing serum adiponectin, preventing PAI-1 increase and inhibiting atherothrombotic signals in PBMCs.This study was supported by public funds: Projects CICYT-BFU2007-60576 and Consolider-Ingenio 2010 (CSD2007-00063, Fun-C-Food) from the Spanish Ministry of Science and Innovation (MICINN) and GERM-06-04486 (Fundación Séneca, Murcia, Spain). Dr. Tomé-Carneiro received a FPI grant from MICINN and Dr. Larrosa received a JAE-DOC contract from the Consejo Superior de Investigaciones Científicas (CSIC, Spain).Peer reviewe

Inhibition of Gastric Lipase as a Mechanism for Body Weight and Plasma Lipids Reduction in Zucker Rats Fed a Rosemary Extract Rich in Carnosic Acid

BACKGROUND: Rosemary (Rosmarinus officinalis L.) extracts (REs) exhibit hepatoprotective, anti-obesity and anti-inflammatory properties and are widely used in the food industry. REs are rich in carnosic acid (CA) and carnosol which may be responsible for some of the biological activities of REs. The aim of this study was to investigate whether inhibition of lipase activity in the gut may be a mechanism by which a RE enriched in CA (40%) modulates body weight and lipids levels in a rat model of metabolic disorders and obesity. METHODS AND PRINCIPAL FINDINGS: RE was administered for 64 days to lean (fa/+) and obese (fa/fa) female Zucker rats and body weight, food intake, feces weight and blood biochemical parameters were monitored throughout the study. Lipase activity (hydrolysis of p-nitrophenylbutyrate) was measured in the gastrointestinal tract at the end of the study and the contents of CA, carnosol and methyl carnosate were also determined. Sub-chronic administration of RE moderately reduced body weight gain in both lean and obese animals but did not affect food intake. Serum triglycerides, cholesterol and insulin levels were also markedly decreased in the lean animals supplemented with RE. Importantly, lipase activity was significantly inhibited in the stomach of the RE-supplemented animals where the highest content of intact CA and carnosol was detected. CONCLUSIONS: Our results confirm that long-term administration of RE enriched in CA moderates weight gain and improves the plasma lipids profile, primarily in the lean animals. Our data also suggest that these effects may be caused, at least in part, by a significant inhibition of gastric lipase and subsequent reduction in fat absorption

Constituyentes Anticancerígenos de la Dieta Mediterránea

La OTRI del Centro Tecnológico Nacional de la Conserva y Alimentación junto con la OTT del Consejo Superior de Investigaciones Científicas, colaboran en el Proyecto AGROCSIC, el cual fue aprobado por el Ministerio de Ciencia y Tecnología y financiado por el Ministerio de Educación y Ciencia. El objetivo principal de esta nueva actuación es estudiar las distintas líneas de trabajo de los Centros del CSIC relacionadas con la alimentación, para transferir sus resultados al sector industrial.Al referirnos a “dieta mediterránea” hablamos de un largo proceso de confluencia entre clima, productos y necesidades de las civilizaciones de los pueblos que han vivido en la cuenca mediterránea. En sentido estricto, deberíamos hablar de dietas mediterráneas, ya que las seguida por poblaciones como Creta, Túnez, Italia, España, etc. no es siempre la misma. Sin embargo, estos paises sí comparten características comunes; consumo elevado: de frutas, hortalizas, legumbres, pasta, cereales, aceite de oliva; moderado: de pescado, cárnico y de productos lácteos, así como de vino y frutos secos. Además de esto, el tipo de cocinado se basa en fritura en baño de aceite de oliva y hervido de alimentos. Actualmente la dieta mediterránea consiste básicamente en mantener una dieta variada/equilibrada y restricciones en el aporte calórico.Peer reviewe

Caracterización de la actividad polifenol oxidasa de aguacate, alcachofa, champiñón, fresa, manzana, níspero y pera / Juan Carlos Espín de Gea ; director Francisco García Cánovas, José Tudela Serrano.

Tesis-Universidad de Murcia.Consulte la tesis en: BCA. GENERAL. ARCHIVO UNIVERSITARIO. D 494.Consulte la tesis en: BCA. GENERAL. ARCHIVO UNIVERSITARIO. T.M.-1440

Tratamiento postcosecha de frutas y hortalizas mediante pulsos de irradiación ultravioleta

Referencia OEPM: P200100910.-- Fecha de solicitud: 19/04/2001.-- Titular: Consejo Superior de Investigaciones Científicas (CSIC).El objeto de la presente invención es el incremento del contenido en resveratrol de uva de mesa mediante pulsos de irradiación en un túnel de lámparas ultravioleta-C. Los pulsos son menores de 1 minuto y la potencia de irradiación puede ser del rango de 30 a 510 W. 2-4 días después del tratamiento, el contenido en resveratrol de la uva tratada aumenta 10 veces o más. De esta manera, simple y barata, se consigue una uva con un significativo aumento en sus propiedades beneficiosas para la salud. El tratamiento también es aplicable a cualquier fruta u hortaliza.Peer reviewe

Study of the oxidation of resveratrol catalyzed by polyphenol oxidase. Effect of polyphenol oxidase, laccase and peroxidase on the antiradical capacity of resveratrol

26 pages, 8 figures, 2 tables.-- Online version published Feb. 2007.This paper reports the study of the oxidation of resveratrol catalyzed by polyphenol oxidase (PPO) as -well as the effect of PPO, laccase and peroxidase on the antiradical capacity of resveratrol (measured as capacity to scavenge 2,2'-azino-bis (3-ethylbenzthiazoline - 6 - sulfonic acid) radicals (ARTS')). Monophenolase activity of mushroom PPO in the presence of resveratrol showed the characteristic lag period (τ) prior the attainment of the steady state rate (Vss). The Michaelis constant (Km) for the oxidation of resveratrol catalyzed by PPO was 45 ± 2 μM at pH 6.8 and it decreased with pH. However, the maximum steady state rate (Vmax) remained constant with pH. Both τ and Vss depended on pH in a sigmoid way. Kinetic and NMR assays confirmed that this compound is a substrate which fulfilled both kinetic and structural reaction mechanisms of PPO. Neither laccase, nor PPO modified the antiradical capacity of resveratrol. However, resveratrol, in the presence of peroxidase, lost its antiradical capacity. A possible correlation between antiradical capacity of resveratrol and its oxidation status is proposed. This paper tries to increase the knowledge about this promising health-beneficial molecule and to demonstrate that PPO could be involved in the oxidation pathway of resveratrol.Dr. Juan Carlos Espin is holder of a “Marie Curie” contract HPMF-CT- 1999-00023 from the European Commission under the framework of the program: “Improving the Human Research Potential and the Socio-Economic knowledge Base”.Peer reviewe

Effect of captopril on mushroom tyrosinase activity in vitro

12 pages, 10 figures.The study presented here demonstrates that the antihypertensive drug captopril ([2S]-N-[3-mercapto-2-methylpropionyl]- -proline) is an irreversible non-competitive inhibitor and an irreversible competitive inhibitor of the monophenolase and diphenolase activities of mushroom tyrosinase when -tyrosine and -DOPA were assayed spectrophotometrically in vitro, respectively. Captopril was rendered unstable by tyrosinase catalysis because of the interaction between the enzymatic-generated product (o-quinone) and captopril to give rise to a colourless conjugate. Therefore, captopril was able to prevent melanin formation. The spectrophotometric recordings of the inhibition of tyrosinase by captopril were characterised by the presence of a lag period prior to the attainment of an inhibited steady state rate. The lag period corresponded to the time in which captopril was reacting with the enzymatically generated o-quinone. Increasing captopril concentrations provoked longer lag periods as well as a concomitant decrease in the tyrosinase activity. Both lag period and steady state rate were dependent of captopril, substrate and tyrosinase concentrations. The inhibition of both monophenolase and diphenolase activities of tyrosinase by captopril showed positive kinetic co-operativity which arose from the protection of both substrate and o-quinone against inhibition by captopril. Inhibition experiments carried out using a latent mushroom tyrosinase demonstrated that captopril only bound the enzyme at its active site. The presence of copper ions only partially prevented but not reverted mushroom tyrosinase inhibition. This could be due to the formation of both copper-captopril complex and disulphide interchange reactions between captopril and cysteine rich domains at the active site of the enzyme.Dr. Juan Carlos Espín is holder of a ‘Marie Curie’ contract HPMF-CT-1999-00023 from the European Commission under the framework of the program: ‘Improving the Human Research Potential and the Socio-Economic Knowledge Base’.Peer reviewe

Polifenoles y salud. Propiedades biológicas de polifenoles de la uva y la granada

3 páginas.-- Sección "Ciencia y sociedad".De estos antioxidantes, destacan los flavonoides: antocianos, flavanoles, flavonoles, flavanonas, flavonas y ácidos hidroxicinámicos y derivados hidroxibenzoicos. Son buenos contra el cáncer -el resveratrol- y enfermedades cardiovasculares.Peer reviewe