Pharmacological properties of polyphenols : Bioavailability, mechanisms of action and biological effects in in vitro studies, animal models and humans

Funding Information: Funding: This work was supported by the following grants from the Instituto de Salud Carlos III CB16/10/00435 (CIBERFES), (PID2019‐110906RB‐I00/AEI/10.13039/501100011033) from the Spanish Ministry of Innovation and Science, PROMETEO/2019/097 de “Consellería, de Sanitat de la Gener‐ alitat Valenciana”, and the EU Funded H2020‐DIABFRAIL‐LATAM (Ref: 825546), European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL), and of the ERA‐NET Co‐ fund ERA‐HDHL (GA No. 696295 of the EU Horizon 2020 Research and Innovation Program). Part of the equipment employed in this work has been funded by Generalitat Valenciana and co‐financed with ERDF funds (OP ERDF of Comunitat Valenciana 2014–2020). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Drugs are bioactive compounds originally discovered from chemical structures present in both the plant and animal kingdoms. These have the ability to interact with molecules found in our body, blocking them, activating them, or increasing or decreasing their levels. Their actions have allowed us to cure diseases and improve our state of health, which has led us to increase the longevity of our species. Among the molecules with pharmacological activity produced by plants are the polyphenols. These, due to their molecular structure, as drugs, also have the ability to interact with molecules in our body, presenting various pharmacological properties. In addition, these compounds are found in multiple foods in our diet. In this review, we focused on discussing the bioavailability of these compounds when we ingested them through diet and the specific mechanisms of action of polyphenols, focusing on studies carried out in vitro, in animals and in humans over the last five years. Knowing which foods have these pharmacological activities could allow us to prevent and aid as concomitant treatment against various pathologies.Peer reviewe

Impact of supplementation with vitamins B6, B12, and/or folic acid on the reduction of homocysteine levels in patients with mild cognitive impairment: A systematic review

Àcid fòlic; Hhomocisteïna; Deteriorament cognitiu lleuÁcido fólico; Homocisteína; Deterioro cognitivo leveFolic acid; Homocysteine; Mild cognitive impairmentHyperhomocysteinemia is an independent predictor of the risk for cognitive decline and may be a result of low levels of vitamins B12, B6, and folate. Previous findings suggest that adequate intake of these vitamins may reduce homocysteine levels. This review aimed to assess the effects of treatment with vitamins B6, B12, and/or folic acid in the homocysteine levels in patients with mild cognitive impairment (MCI). A systematic literature review was conducted in EMBASE, MEDLINE®, PsycINFO, and Cochrane Central Register of Controlled Trials. The research question was formulated using the Population, Intervention, Comparison, and Outcome (PICO) framework: in patients with MCI (P); what is the efficacy of vitamins B6, B12, and/or folic acid intake (I); compared with baseline values, and/or compared with controls (C); in reducing homocysteine levels from baseline (O). A total of eight primary studies with a total of 1,140 participants were included in the review. Four were randomized controlled trials, one was a quasi-controlled trial, and three were observational studies. All studies included folic acid in their intervention, seven vitamin B12, and four vitamin B6. Mean (SD) length of the intervention period was 18.8 (19.3) months, ranging from 1 to 60 months. All studies showed a statistically significant decrease in homocysteine levels in groups treated with vitamins B6, B12, and/or folic acid compared to controls, with a mean decline of homocysteine concentration of 31.9% in the intervention arms whereas it increased by 0.7% in the control arm. This review identified evidence of a reduction of plasma homocysteine levels in MCI patients taking vitamins B6, B12, and/or folic acid supplements, with statistically significant declines being observed after 1 month of supplementation. Findings support that supplementation with these vitamins might be an option to reduce homocysteine levels in people with MCI and elevated plasma homocysteine.Nestlé Health Science, Switzerlan

The science of storytelling: different levels of narrative integration in teaching innovation applied to Human Physiology

[EN] The incorporation of narrative features into teaching materials of different formats, such as graphic and audiovisual ones, has proven to be an efficient way of encouraging student motivation. Besides, it strengthens the teaching of abstract concepts like those frequent in experimental sciences, such as Physiology, a basic subject in life sciences studies. From the Department of Physiology of the University of Valencia we present the creation of a teaching innovation group focused on the development of Narrative Physiology, FISIONARR, with the aim of promoting the narrative nature of teaching Physiology through two strategic lines. The first one focuses on graphic narrative and its integration as a teaching tool at different levels; the second deals with the generation of audiovisual narrative. In this sense, specific audiovisual material has been prepared for a series of videos entitled " Invisible Physiology", and as a conductive element of the digital educational escape room "Alimental, querida Watson".[ES] La incorporación de elementos narrativos en material docente de distintos formatos gráficos y audiovisuales es una manera eficiente de incentivar la motivación del estudiantado y de reforzar la docencia de conceptos abstractos como los relacionados con ciencias experimentales como la Fisiología, materia básica en estudios de ciencias de la salud. Desde el Departamento de Fisiología de la Universitat de València presentamos la creación de un grupo de innovación docente centrado en el uso de la Fisiología Narrativa, FISIONARR, con el objetivo de potenciar el carácter narrativo de la docencia en Fisiología a través de dos líneas estratégicas. La primera de ellas se centra en la narrativa gráfica y en su integración como herramienta docente a distintos niveles. La segunda trata sobre la generación de narrativa audiovisual y concretamente de ha elaborado material para una serie de videos titulados “La Fisiología Invisible” y como elemento conductor de la escape room educacional digital “Alimental, querida Watson”.Olaso Gonzalez, G.; Calvo Saiz, C.; González Cabo, P.; García Giménez, JL.; Gómez-Cabrera, MC.; Arribas Rodríguez, S.; Gal Iglesias, B.... (2023). La ciencia de contar historias: distintos niveles de integración narrativa en innovación docente aplicada a la Fisiología Humana. Editorial Universitat Politècnica de València. 1050-1060. https://doi.org/10.4995/INRED2023.2023.166551050106

European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS).

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.The EU-ROS consortium (COST Action BM1203) was supported by the European Cooperation in Science and Technology (COST). The present overview represents the final Action dissemination summarizing the major achievements of COST Action BM1203 (EU-ROS) as well as research news and personal views of its members. Some authors were also supported by COST Actions BM1005 (ENOG) and BM1307 (PROTEOSTASIS), as well as funding from the European Commission FP7 and H2020 programmes, and several national funding agencies

Impact of supplementation with vitamins B 6

Àcid fòlic; Hhomocisteïna; Deteriorament cognitiu lleuÁcido fólico; Homocisteína; Deterioro cognitivo leveFolic acid; Homocysteine; Mild cognitive impairmentHyperhomocysteinemia is an independent predictor of the risk for cognitive decline and may be a result of low levels of vitamins B12, B6, and folate. Previous findings suggest that adequate intake of these vitamins may reduce homocysteine levels. This review aimed to assess the effects of treatment with vitamins B6, B12, and/or folic acid in the homocysteine levels in patients with mild cognitive impairment (MCI). A systematic literature review was conducted in EMBASE, MEDLINE®, PsycINFO, and Cochrane Central Register of Controlled Trials. The research question was formulated using the Population, Intervention, Comparison, and Outcome (PICO) framework: in patients with MCI (P); what is the efficacy of vitamins B6, B12, and/or folic acid intake (I); compared with baseline values, and/or compared with controls (C); in reducing homocysteine levels from baseline (O). A total of eight primary studies with a total of 1,140 participants were included in the review. Four were randomized controlled trials, one was a quasi-controlled trial, and three were observational studies. All studies included folic acid in their intervention, seven vitamin B12, and four vitamin B6. Mean (SD) length of the intervention period was 18.8 (19.3) months, ranging from 1 to 60 months. All studies showed a statistically significant decrease in homocysteine levels in groups treated with vitamins B6, B12, and/or folic acid compared to controls, with a mean decline of homocysteine concentration of 31.9% in the intervention arms whereas it increased by 0.7% in the control arm. This review identified evidence of a reduction of plasma homocysteine levels in MCI patients taking vitamins B6, B12, and/or folic acid supplements, with statistically significant declines being observed after 1 month of supplementation. Findings support that supplementation with these vitamins might be an option to reduce homocysteine levels in people with MCI and elevated plasma homocysteine.Nestlé Health Science, Switzerlan

Modulating Oxidant Levels to Promote Healthy Aging

International audienceRecent Advances: This review discusses the importance of the modulation of the oxidant levels through physiological strategies such as physical exercise or genetic manipulations such as the overexpression of antioxidant enzymes, in the promotion of healthy aging. Critical Issues: We have divided the review into five different sections. In the first two sections of the article "Oxidants are signals" and "Exercise training is an antioxidant," we discuss the main sources of free radicals during muscle contraction and their role, as hormetic substances, in the regulation of two main muscle adaptations to exercise in skeletal muscle; that is, mitochondrial biogenesis and the endogenous antioxidant defense. In the third section of the review, we deal with "the energy collapse in aging." The increased rate of reactive oxygen species (ROS) production and the low rate of mitochondria biosynthesis in the old cells are examined. Finally, in the fourth and fifth sections entitled "Overexpression of antioxidants enzymes in healthy aging" and "Exercise, longevity, and frailty," we consider the importance of the potentiation of the cellular defenses in health span and in life span. Future Directions: A correct manipulation of the ROS generation, directing these species to their physiological signaling role and preventing their deleterious effects, would allow the promotion of healthy aging

Real-Life Outcomes of a Multicomponent Exercise Intervention in Community-Dwelling Frail Older Adults and Its Association with Nutritional-Related Factors

Most of the studies on physical exercise in older adults have been conducted through randomized clinical trials performed under tight experimental conditions. Data regarding Real-Life physical exercise intervention programs in older adults with different conditions and in different settings, are lacking. This is an interventional, prospective and pragmatic Real-Life study in which fifty sedentary and frail individuals were enrolled. We aimed at determining if a Real-Life exercise intervention outweighs previously reported improvements in a Clinical Trial (NCT02331459). We found higher improvements in the Real-Life exercise intervention vs. the Clinical Trial in functional parameters, such as Fried’s frailty criteria, Tinetti, Barthel and Lawton & Brody scales. Similar results were found in the dietary habits, emotional and social networking outcomes determined through the Short-MNA, Yesavage, EuroQol and Duke scales. The Real-Life intervention led to a significant reduction in the number of falls, visits to the primary care centers and emergency visits when compared to the results of our previously published Clinical Trial. The implementation of a Real-Life exercise intervention is feasible and should be a major priority to improve health-span in the older population

Moderate Red Wine Consumption Increases the Expression of Longevity-Associated Genes in Controlled Human Populations and Extends Lifespan in Drosophila melanogaster

The beneficial effects of moderate red wine consumption on cardiovascular health are well known. The composition of red wine includes several compounds, such as the phytoestrogen resveratrol, that exert these beneficial effects, although not all the mechanisms by which they act are known. Our aim was to study the effect of red wine consumption on longevity-related genes in controlled human populations, such as cloistered nuns. We found that the expression of catalase, manganese-superoxide dismutase, Sirt1, and p53 was increased in peripheral blood mononuclear cells after 14 days of moderate red wine consumption. This increase was accompanied by an enhanced metabolic wellness: fatty acids, cholesterol, branched chain amino acids (isoleucine and leucine), ketone bodies (acetoacetate), bacterial co-metabolites (trimethylamine), and cellular antioxidants (taurine) contributed to a change in metabolic profile after moderate red wine consumption by the nuns. No serious unwanted side effects were observed. Finally, we tested the effect of moderate red wine consumption on longevity in a controlled animal population, such as D. melanogaster, and found that it increased average life span by 7%. In conclusion, moderate red wine consumption increases the expression of key longevity-related genes and improves metabolic health in humans and increases longevity in flies

Glucose 6-P Dehydrogenase—An Antioxidant Enzyme with Regulatory Functions in Skeletal Muscle during Exercise

Hypomorphic Glucose 6-P dehydrogenase (G6PD) alleles, which cause G6PD deficiency, affect around one in twenty people worldwide. The high incidence of G6PD deficiency may reflect an evolutionary adaptation to the widespread prevalence of malaria, as G6PD-deficient red blood cells (RBCs) are hostile to the malaria parasites that infect humans. Although medical interest in this enzyme deficiency has been mainly focused on RBCs, more recent evidence suggests that there are broader implications for G6PD deficiency in health, including in skeletal muscle diseases. G6PD catalyzes the rate-limiting step in the pentose phosphate pathway (PPP), which provides the precursors of nucleotide synthesis for DNA replication as well as reduced nicotinamide adenine dinucleotide phosphate (NADPH). NADPH is involved in the detoxification of cellular reactive oxygen species (ROS) and de novo lipid synthesis. An association between increased PPP activity and the stimulation of cell growth has been reported in different tissues including the skeletal muscle, liver, and kidney. PPP activity is increased in skeletal muscle during embryogenesis, denervation, ischemia, mechanical overload, the injection of myonecrotic agents, and physical exercise. In fact, the highest relative increase in the activity of skeletal muscle enzymes after one bout of exhaustive exercise is that of G6PD, suggesting that the activation of the PPP occurs in skeletal muscle to provide substrates for muscle repair. The age-associated loss in muscle mass and strength leads to a decrease in G6PD activity and protein content in skeletal muscle. G6PD overexpression in Drosophila Melanogaster and mice protects against metabolic stress, oxidative damage, and age-associated functional decline, and results in an extended median lifespan. This review discusses whether the well-known positive effects of exercise training in skeletal muscle are mediated through an increase in G6PD

Personalized multicomponent physical exercise program for the prevention and reversal of frailty in the elderly

International audienc