Metabolism of natural antioxidants: evaluation of the pathways involved in the in vivo biotransformation of tyrosol into hydroxytyrosol

Hydroxytyrosol [2-(3,4-dihydroxyphenyl)ethanol], a potent bioactive molecule mainly present in virgin olive oil and to a lower extent in wine, is also a by-product of dopamine metabolism. In a previous clinical trial designed to assess the effects of moderate wine intake it was found that hydroxytyrosol urinary recoveries were higher than the corresponding to the dose administered, suggesting an endogenous formation. The aim of the present work was to assess new mechanisms responsible for hydroxytyrosol generation by using an array of methodologies and studies ranging from in vitro assays to in vivo experiments in animal models and humans. The mechanisms identified as being involved in the generation of hydroxytyrosol were (1) CYP2A6/CYP2D6-catalyzed tyrosol-to-hydroxytyrosol biotransformation, (2) ethanol-induced increase in tyrosol bioavailability, and (3) alteration of dopamine oxidative metabolism due to ethanol. Considering these observations, it is postulated that hydroxytyrosol may contribute significantly to the health effects derived from moderate wine intake.L’hidroxitirosol [2-(3,4-dihidroxiphenil)etanol], una potent molècula bioactiva present de forma rellevant a l’oli d’oliva verge i minoritàriament al vi, és també un producte del metabolisme de la dopamina. En un assaig clínic previ dissenyat per avaluar els efectes del consum moderat de vi es trobà que les recuperacions urinàries d’hidroxitirosol eren superiors a la dosi administrada, suggerint-ne una gènesi endògena. L’objectiu del present treball fou estudiar nous mecanismes responsables de la generació d’hidroxitirosol mitjançant diverses tècniques i estudis, des d’assajos in vitro a experiments in vivo en animals i humans. Els mecanismes involucrats a la generació d’hidroxitirosol són (1) la biotransformació de tirosol a hidroxitirosol catalitzada per CYP2A6/CYP2D6, (2) l’augment a la biodisponibilitat del tirosol induïda per l’etanol, i (3) l’alteració del metabolisme oxidatiu de la dopamina per l’etanol. Globalment, aquestes observacions donen a l’hidroxitirosol un paper clau en la comprensió dels efectes beneficiosos associats al consum moderat de vi

Metabolism of natural antioxidants: evaluation of the pathways involved in the in vivo biotransformation of tyrosol into hydroxytyrosol

Hydroxytyrosol [2-(3,4-dihydroxyphenyl)ethanol], a potent bioactive molecule mainly present in virgin olive oil and to a lower extent in wine, is also a by-product of dopamine metabolism. In a previous clinical trial designed to assess the effects of moderate wine intake it was found that hydroxytyrosol urinary recoveries were higher than the corresponding to the dose administered, suggesting an endogenous formation. The aim of the present work was to assess new mechanisms responsible for hydroxytyrosol generation by using an array of methodologies and studies ranging from in vitro assays to in vivo experiments in animal models and humans. The mechanisms identified as being involved in the generation of hydroxytyrosol were (1) CYP2A6/CYP2D6-catalyzed tyrosol-to-hydroxytyrosol biotransformation, (2) ethanol-induced increase in tyrosol bioavailability, and (3) alteration of dopamine oxidative metabolism due to ethanol. Considering these observations, it is postulated that hydroxytyrosol may contribute significantly to the health effects derived from moderate wine intake.L’hidroxitirosol [2-(3,4-dihidroxiphenil)etanol], una potent molècula bioactiva present de forma rellevant a l’oli d’oliva verge i minoritàriament al vi, és també un producte del metabolisme de la dopamina. En un assaig clínic previ dissenyat per avaluar els efectes del consum moderat de vi es trobà que les recuperacions urinàries d’hidroxitirosol eren superiors a la dosi administrada, suggerint-ne una gènesi endògena. L’objectiu del present treball fou estudiar nous mecanismes responsables de la generació d’hidroxitirosol mitjançant diverses tècniques i estudis, des d’assajos in vitro a experiments in vivo en animals i humans. Els mecanismes involucrats a la generació d’hidroxitirosol són (1) la biotransformació de tirosol a hidroxitirosol catalitzada per CYP2A6/CYP2D6, (2) l’augment a la biodisponibilitat del tirosol induïda per l’etanol, i (3) l’alteració del metabolisme oxidatiu de la dopamina per l’etanol. Globalment, aquestes observacions donen a l’hidroxitirosol un paper clau en la comprensió dels efectes beneficiosos associats al consum moderat de vi

Potential Role of (-)-Epigallocatechin-3-Gallate (EGCG) in the Secondary Prevention of Alzheimer Disease

Medical advances in the last decades have increased the average life expectancy, but also the incidence and prevalence of age-associated neurodegenerative diseases. Alzheimer's disease (AD) is one of the most common neurodegenerative diseases and the most prevalent type of dementia. A plethora of different mechanisms contribute to AD, among which oxidative stress plays a key role in its development and progression. So far, there are no pharmacological treatments available and the current medications are mainly symptomatic. In the last years, dietary polyphenols have gained research attention due to their interesting biological activities, and more specifically their antioxidant properties. (-)- Epigallocatechin-3-gallate (EGCG) is a natural flavanol that has been extensively studied regarding its potential effects in AD. In this review we present the current in vitro and in vivo experimentation regarding the use of EGCG in AD. We also review the complex mechanisms of action of EGCG, not only limited to its antioxidant activity, which may explain its beneficial health effects.http://dx.doi.org/10.2174/1389450116666150825113655This work was supported by grants, donations and agreements from Fondation Jérôme Lejeune (Paris, France), Instituto de Salud Carlos III FEDER, (PI11/00744), MINECO (SAF2010- 19434, MTM2012-38067-C02-01 and SAF2013-49129-C1- R), EU (Era Net Neuron PCIN-2013-060) co-financed by European Regional Development Fund, DIUE de la Generalitat de Catalunya (SGR 2009/1450, SGR 2014/464 SGR 2014/1125). We acknowledge support of the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013-2017’, SEV-2012-0208.Jose Rodríguez-Morató was supported by a FI-DGR 2013 predoctoral fellowship from the Generalitat de Catalunya

Modulation of Nrf2 by olive oil and wine polyphenols and neuroprotection

Strong adherence to a Mediterranean diet is associated with improved cognitive function and a lower prevalence of mild cognitive impairment. Olive oil and red wine are rich sources of polyphenols which are responsible in part for the beneficial effects on cognitive functioning. Polyphenols induce endogenous antioxidant defense mechanisms by modulating transcription factors such as the nuclear factor (erythroid-derived 2)-like 2 (Nrf2). This review discusses the scientific data supporting the modulating effect of olive oil and red wine polyphenols on Nrf2 expression, and the potential health benefits associated with cognitive functioning

Comparison of the postprandial metabolic fate of U- 13 C stearic acid and U- 13 C oleic acid in postmenopausal women

Objective: Compare the postprandial fatty acid metabolism of isotopically labeled stearate (U-13C18:0) and oleate (U-13C18:1). Approach and Results: In conjunction with a randomized-controlled crossover trial, 6 hypercholesterolemic postmenopausal women (≥50 years; body mass index: 25.6±3.0 kg/m2; LDL [low-density lipoprotein]-cholesterol ≥110 mg/dL) consumed isocaloric diets enriched in 18:0 or 18:1 (10%-15% E) for 5 weeks each. On day 1 of week 5, following a 12-hour fast, participants receive their experimental diet divided into 13 hourly meals beginning at 8 am. U-13C18:0 or U-13C18:1 was incorporated into the 1:00 pm meal (1.0 mg/kg body weight). Serial blood and breath samples were collected over 12 hours and fasting samples at 24 and 48 hours. Plasma and lipid subfraction fatty acid profiles were assessed by gas chromatography-flame ionization detector, isotope-enrichment by liquid chromatography time-of-flight mass spectrometry, and fatty acid oxidation rate (expired 13CO2) by isotope ratio mass spectrometry. Both diets resulted in similar plasma LDL-cholesterol concentrations. Kinetic curves showed that U-13C18:0 had a higher plasma area under the curve (66%), lower plasma clearance rate (-46%), and a lower cumulative oxidation rate (-34%) than U-13C18:1. Three labeled plasma metabolites of U-13C18:0 were detected: 13C16:0, 13C16:1, and 13C18:1. No plasma metabolites of U-13C18:1 were detected within the study time-frame. Higher incorporation of 18:0 in cholesteryl ester and triglyceride fractions was observed on the 18:0 compared with the 18:1 diet. Conclusions: The neutrality of 18:0 on plasma LDL-cholesterol concentrations is not attributable to a single factor. Compared with 18:1, 18:0 had higher plasma area under the curve because of lower clearance and oxidation rates, underwent both a direct and a multistage conversion to 18:1, and was preferentially incorporated into cholesteryl esters and triglycerides.This work was supported by Human Nutrition Research Center on Aging Pilot funds; United States Department of Agriculture (USDA)-NIFA-AFRI-003397, and USDA 1950-51000-072-02S. J. Rodríguez-Morató acknowledges funding from the EU Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 712949 (TECNIOspring PLUS) and from ACCIÓ. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of authors and do not necessarily reflect the views of the USDA

Cranberries attenuate animal-based diet-induced changes in microbiota composition and functionality: a randomized crossover controlled feeding trial

Cranberries have multiple health effects but their impact on gut microbiota has not been examined in randomized controlled feeding trials. We evaluated the relationship between the microbiota and cranberries in the context of an animal-based diet. In a randomized, double-blind, cross-over, controlled design trial, 11 healthy adults consumed for 5 days each a control diet (animal-based diet plus 30 g/day placebo powder) and a cranberry diet (animal-based diet plus 30 g/day freeze-dried whole cranberry powder). The animal-based diet included meats, dairy products, and simple sugars. Stool, urine, and blood samples were obtained before and after each intervention phase. As compared to the pre-control diet, control diet modified 46 taxonomic clades, including an increase in the abundance of Firmicutes and decrease in Bacteroidetes. Moreover, it increased bacteria-derived deoxycholic acid and decreased acetate and butyrate in stool. As compared to the post-intervention phase of control diet, the cranberry diet modified 9 taxonomic clades, including a decrease in the abundance of Firmicutes and increase in Bacteroidetes. Further, the cranberry diet attenuated control diet-induced increase in secondary bile acids and decrease in short-chain fatty acids (SCFA), and increased urinary anthocyanins and bacterially derived phenolic acids. No changes were found in fecal trimethylamine and plasma cytokines. In conclusion, an animal-based diet altered the microbiota composition to a less favorable profile, increased carcinogenic bile acids, and decreased beneficial SCFA. Cranberries attenuated the impact of the animal-based diet on microbiota composition, bile acids, and SCFA, evidencing their capacity to modulate the gut microbiota.This research was funded by Cranberry Institute and United States Department of Agriculture (USDA) [1950-51000-087]. JRM acknowledges funding from European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 712949 (TECNIOspring PLUS) and from ACCI

Olive oil phenolic compounds' activity against age-associated cognitive decline: clinical and experimental evidence

Epidemiological studies have shown that consuming olive oil rich in phenolic bioactive compounds is associated with a lower risk of neurodegenerative diseases and better cognitive performance in aged populations. Since oxidative stress is a common hallmark of age-related cognitive decline, incorporating exogenous antioxidants could have beneficial effects on brain aging. In this review, we firstly summarize and critically discuss the current preclinical evidence and the potential neuroprotective mechanisms. Existing studies indicate that olive oil phenolic compounds can modulate and counteract oxidative stress and neuroinflammation, two relevant pathways linked to the onset and progression of neurodegenerative processes. Secondly, we summarize the current clinical evidence. In contrast to preclinical studies, there is no direct evidence in humans of the bioactivity of olive oil phenolic compounds. Instead, we have summarized current findings regarding nutritional interventions supplemented with olive oil on cognition. A growing body of research indicates that high consumption of olive oil phenolic compounds is associated with better preservation of cognitive performance, conferring an additional benefit, independent of the dietary pattern. In conclusion, the consumption of olive oil rich in phenolic bioactive compounds has potential neuroprotective effects. Further research is needed to understand the underlying mechanisms and potential clinical applications

Potential role of olive oil phenolic compounds in the prevention of neurodegenerative diseases

Adherence to the Mediterranean Diet (MD) has been associated with a reduced incidence of neurodegenerative diseases and better cognitive performance. Virgin olive oil, the main source of lipids in the MD, is rich in minor phenolic components, particularly hydroxytyrosol (HT). HT potent antioxidant and anti-inflammatory actions have attracted researchers' attention and may contribute to neuroprotective effects credited to MD. In this review HT bioavailability and pharmacokinetics are presented prior to discussing health beneficial effects. In vitro and in vivo neuroprotective effects together with its multiple mechanisms of action are reviewed. Other microconstituents of olive oil are also considered due to their potential neuroprotective effects (oleocanthal, triterpenic acids). Finally, we discuss the potential role of HT as a therapeutic tool in the prevention of neurodegenerative diseases