The effects of polyphenols and other bioactives on human health

Although deficiencies in polyphenol intake do not result in specific deficiency diseases, adequate intake of polyphenols could confer health benefits, especially with regard to chronic diseases. Tea, cocoa, fruits, and berries, as well as vegetables, are rich in polyphenols. Flavan-3-ols from cocoa have been found to be associated with a reduced risk of stroke, myocardial infarction, and diabetes, as well as improvements in lipids, endothelial-dependent blood flow and blood pressure, insulin resistance, and systemic inflammation. The flavonoid quercetin and the stilbene resveratrol have also been associated with cardiometabolic health. Although polyphenols have been associated with improved cerebral blood flow, evidence of an impact on cognition is more limited. The ability of dietary polyphenols to produce clinical effects may be due, at least in part, to a bi-directional relationship with the gut microbiota. Polyphenols can impact the composition of the gut microbiota (which are independently associated with health benefits), and gut bacteria metabolize polyphenols into bioactive compounds that produce clinical benefits. Another critical interaction is that of polyphenols with other phytochemicals, which could be relevant to interpreting the health parameter effects of polyphenols assayed as purified extracts, whole foods, or whole food extracts

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

Diet-derived bioavailable metabolites to tackle diabetes

Funding Information: Funding: This study was funded by Fundação para a Ciência e Tecnologia (FCT)/Ministério da Ciência e do Ensino Superior, grant numbers PTDC/BIA-MOL/31104/2017 (RM) and UIDB/04567/2020 and UIDP/ 04567/2020 (CBIOS). iNOVA4Health Research Unit (LISBOA—01–0145—FEDER—007344), which is cofunded by FCT/Ministério da Ciência e do Ensino Superior, through national funds, and by FEDER under the PT2020 Partnership Agreement, is also acknowledged. Authors would like to acknowledge FCT for the financial support of AFR (PD/BD/135504/2018); SF (UI/BD/151421/2021), and RM (CEEC/04567/CBIOS/2020).Diabetes remains one of the leading causes of deaths and co-morbidities in the world, with tremendous human, social and economic costs. Therefore, despite therapeutics and technological advancements, improved strategies to tackle diabetes management are still needed. One of the suggested strategies is the consumption of (poly)phenols. Positive outcomes of dietary (poly)phenols have been pointed out towards different features in diabetes. This is the case of ellagitannins, which are present in numerous foodstuffs such as pomegranate, berries, and nuts. Ellagitannins have been reported to have a multitude of effects on metabolic diseases. However, these compounds have high molecular weight and do not reach circulation at effective concentrations, being metabolized in smaller compounds. After being metabolized into ellagic acid in the small intestine, the colonic microbiota hydrolyzes and metabolizes ellagic acid into dibenzopyran-6-one derivatives, known as urolithins. These low molecular weight compounds reach circulation in considerable concentrations ranging until micromolar levels, capable of reaching target tissues. Different urolithins are formed throughout the metabolization process, but urolithin A, isourolithin A, and urolithin B, and their phase-II metabolites are the most frequent ones. In recent years, urolithins have been the focus of attention in regard to their effects on a multiplicity of chronic diseases, including cancer and diabetes. In this review, we will discuss the latest advances about the protective effects of urolithins on diabetes.publishersversionpublishe

Identification of Botanical Biomarkers in Argentinean Diplotaxis Honeys: Flavonoids and Glucosinolates

To select and establish floral biomarkers of the botanical origin ofDiplotaxis tenuifoliahoneys, the flavonoids and glucosinolates present in bee-deposited nectar collected from hive combs (unripe honey) and mature honey from the same hives fron which the unripe honey samples were collected were analyzed by LC-UV-PAD-ESI-MSn. Glycosidic conjugates of the flavonols quercetin, kaempferol, and isorhamnetin were detected and characterized in unripe honey.D. tenuifoliamature honeys contained the aglycones kaempferol, quercetin, and isorhamnetin. The differences between the phenolic profiles of mature honey and freshly deposited honey could be due to hydrolytic enzymatic activities. Aliphatic and indole glucososinolates were analyzed in unripe and mature honeys, this being the first report of the detection and characterization of glucosinolates as honey constituents. Moreover, these honey samples contained different amounts of propolis-derived flavonoid aglycones (1765−3171 μg/100 g) and hydroxycinnamic acid derivatives (29−1514 μg/100 g). Propolis flavonoids were already present in the freshly deposited nectar, showing that the incorporation of these compounds to honey occurs at the early steps of honey production. The flavonoids quercetin, kaempferol, and isorhamnetin and the glucosinolates detected in the samples could be used as complementary biomarkers for the determination of the floral origin of ArgentineanDiplotaxishoneys

Estabilidad de los compuestos bioactivos de fresa sometida a tratamientos postcosecha oxidativos y atmosféricos

[SPA] La fresa es un fruto muy perecedero que necesita de tratamientos de postcosecha para prolongar su vida útil. En este estudio, se ha evaluado el uso de distintos tratamientos postcosecha: ozono (O3) gas, luz ultravioleta (UV-C) y el envasado en atmósferas modificadas (EAM), enriquecidas en O2 y/o CO2, en los constituyentes bioactivos de la fresa. En un primer ensayo, fresa de la variedad Camarosa fue sometida a diferentes dosis de luz UV-C (1, 5, 10 y 15 kJ m-2) y O3 gas (5000, 10000, 150000, 20000 ppm) con el objetivo de seleccionar las dosis óptimas de los tratamientos oxidativos. Se observó que las dosis más bajas de luz UV-C y O3 gas fueron los únicos tratamientos que no perjudicaron la calidad organoléptica del fruto, por lo que 1 kJ m-2 de luz UV-C y 5000 ppm de O3 gas se seleccionaron para los ensayos de conservación en atmósfera modificada. La estabilidad de los compuestos bioactivos presentes en fresa tratada con distintos tratamientos postcosecha se evaluaron a lo largo de 12 días de conservación a 2ºC. En los dos estudios llevados a cabo se observó que dosis de 1 kJ m-2 de luz UV-C y 5000 ppm O3 gaseoso redujeron de una forma significativa el contenido fenólico de las fresas, al igual que la conservación en alto O2 (≥ 60 kPa) y alto CO2 (≥10 kPa) a partir del quinto día de conservación. La calidad organoléptica de la fresa fue puntuada como buena a lo largo de la conservación, excepto por el sabor de las fresas conservadas en EAM, evaluada como regular al cabo de 9 y 12 días de conservación. [ENG] The short postharvest self-life of strawberries encourages the use of decay-control techniques. In this study, modified atmosphere packaging (MAP), gaseous ozone (O3), and ultraviolet-C (UV-C) light have been evaluated as novel postharvest techniques to prolong self-life and maintain quality of strawberries. In the first experience, strawberries of the variety Camarosa were treated with different doses of UV-C light (1, 5, 10 and 15 kJ m-2) and gaseous O3 (5000, 10000, 150000, 20000 ppm) to adjust the optimal doses of theses oxidative treatments. The lowest UV-C (1 kJm-2) and gaseous O3 (5000 ppm) doses were selected for the storage assays, as the rest of the doses provoked browning and drying of the strawberry calyx. The effect of UV-C light, gaseous O3, superatmospheric O2 and CO2-enriched atmospheres applied individually and in combination on the bioactive constituents and selflife of strawberries were evaluated during 12 days at 2ºC. In general, phenolic content of UVC and gaseous O3 treated strawberries was significantly reduced when compared to untreated samples. After 5 days, strawberries stored under superatmospheric O2 (≥ 60 kPa) and CO2- enriched (≥10 kPa) concentration showed lower total phenolic content. In general, overall quality was good in all samples throughout the self-life except for flavour scores of MAP strawberries, which were clearly lower than air-stored samples after 9 and 12 days of storage.Agradecimientos a la Comisión Europea FLAVO (Flavonoids in fruits and vegetables: their impact on food quality, nutrition and human health) y al proyecto AGL2004-03060 por la financiación económica

Targeted and Untargeted Metabolomics to Explore the Bioavailability of the Secoiridoids from a Seed/Fruit Extract (Fraxinus angustifolia Vahl) in Human Healthy Volunteers: A Preliminary Study

The bark, seeds, fruits and leaves of the genus Fraxinus (Oleaceae) which contain a wide range of phytochemicals, mostly secoiridoid glucosides, have been widely used in folk medicine against a number of ailments, yet little is known about the metabolism and uptake of the major Fraxinus components. The aim of this work was to advance in the knowledge on the bioavailability of the secoiridoids present in a Fraxinus angustifolia Vahl seed/fruit extract using both targeted and untargeted metabolomic analyses. Plasma and urine samples from nine healthy volunteers were taken at specific time intervals following the intake of the extract and analyzed by UPLC-ESI-QTOF. Predicted metabolites such as tyrosol and ligstroside-aglycone glucuronides and sulfates were detected at low intensity. These compounds reached peak plasma levels 2 h after the intake and exhibited high variability among the participants. The ligstroside-aglycone conjugates may be considered as potential biomarkers of the Fraxinus secoiridoids intake. Using the untargeted approach we additionally detected phenolic conjugates identified as ferulic acid and caffeic acid sulfates, as well as hydroxybenzyl and hydroxyphenylacetaldehyde sulfate derivatives which support further metabolism of the secoiridoids by phase I and (or) microbial enzymes. Overall, the results of this study suggest low uptake of intact secoiridoids from a Fraxinus angustifolia Vahl extract in healthy human volunteers and metabolic conversion by esterases, glycosidases, and phase II sulfo- and glucuronosyl transferases to form smaller conjugated derivatives.This work was financially supported by the Centre for the Development of Industrial Technology (CDTI) from the Spanish Government (NEMAF project) and R.G.V., P.F-B. and M-T.G.C. are participating to the COST Action FA1403 Positive (Interindividual variation in response to consumption of plant food bioactives and determinants involved). We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).Peer reviewe

Bioactive components and antioxidant and antibacterial activities of different varieties of honey: a screening prior to clinical application

This study assessed 16 different honey samples in order to select the best one for therapeutic purposes. First, a study of honey's main bioactive compounds was carried out. Then phenolic profiles were determined and specific compounds quantified using a HPLC system coupled to a mass spectrometer. Then, antioxidant activity, by three in vitro methods, and antibacterial activity against reference strains and clinical isolates were evaluated. Great variability among samples was observed regarding ascorbic acid (between 0.34 ± 0.00 and 75.8 ± 0.41 mg/100 g honey; p < 0.001), total phenolic compounds (between 23.1 ± 0.83 and 158 ± 5.37 mg/100 g honey; p < 0.001), and total flavonoid contents (between 1.65 ± 0.11 and 5.93 ± 0.21 mg/100 g honey; p < 0.001). Forty-nine different phenolic compounds were detected, but only 46 of them were quantified by HPLC. The concentration of phenolic compounds and the phenolic profiles varied widely among samples (between 1.06 ± 0.04 and 18.6 ± 0.73 mg/100 g honey; p < 0.001). Antioxidant activity also varied significantly among the samples. All honey varieties exhibited antibacterial activity against both reference and clinical strains (effective concentrations ranged between 0.05 and 0.40 g/mL depending on the honey sample and bacteria tested). Overall, samples with better combinations of bioactive properties were avocado and chestnut honeys.This work was supported by the ConsejeriaFundinǵ de Sanidad of Junta de Castilla y Leoń (Spain); under grant GRS 551/A/10. P.C.-F. was funded by the Consejeriá de Educacioń of Junta de Castilla y Leoń and European Social Fund. Notes The authors declare no competing financial interest.info:eu-repo/semantics/publishedVersio

Separation of Isomeric Forms of Urolithin Glucuronides Using Supercritical Fluid Chromatography

Producción CientíficaUrolithins are gut microbiota metabolites produced in humans after consuming foods containing ellagitannins and ellagic acid. Three urolithin metabotypes have been reported for different individuals depending on the final urolithins produced. After absorption, they are conjugated with glucuronic acid (phase II metabolism), and these are the main circulating metabolites in plasma and reach different tissues. Different regioisomeric isomers of urolithin glucuronides have been described. Still, their identification and quantification in humans have not been properly reported due to resolution limitations in their analysis by reversed-phase high-performance liquid chromatography. In the present study, we report a novel method for separating these isomers using supercritical fluid chromatography. With this method, urolithin A 3- and 8-glucuronide, isourolithin A 3- and 9- glucuronide, and urolithin B 3-glucuronide (8-hydroxy urolithin 3-glucuronide; 3-hydroxy urolithin 8-glucuronide; 3-hydroxyurolithin 9-glucuronide; 9-hydroxyurolithin 3-glucuronide; and urolithin 3-glucuronide) were separated in less than 15 min. The proposed method was applied to successfully analyze these metabolites in urine samples from different volunteers belonging to different metabotypes.Taif University (TURSP- HC2021/3

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