Insights into the Neuroprotective Potential of Epicatechin: Effects against Aß-Induced Toxicity in Caenorhabditis elegans.

Medical therapies to avoid the progression of Alzheimer's disease (AD) are limited to date. Certain diets have been associated with a lower incidence of neurodegenerative diseases. In particular, the regular intake of foods rich in polyphenols, such as epicatechin (EC), could help prevent or mitigate AD progression. This work aims to explore the neuroprotective effects of EC using different transgenic strains of Caenorhabditis elegans, which express human Aß1-42 peptides and contribute to elucidating the mechanisms involved in the effects of EC in AD. The performed assays indicate that this flavan-3-ol was able to reduce the signs of ß-amyloid accumulation in C. elegans, improving motility and chemotaxis and increasing survival in transgenic strain peptide producers compared to nematodes not treated with EC. The neuroprotective effects exhibited by EC in C. elegans could be explained by the modulation of inflammation and stress-associated genes, as well as autophagy, microgliosis, and heat shock signaling pathways, involving the regulation of cpr-5, epg-8, ced-7, ZC239.12, and hsp-16 genes. Overall, the results obtained in this study support the protective effects of epicatechin against Aß-induced toxicity.

Evaluation of the polyphenolic profile of native Ecuadorian stingless bee honeys (Tribe: Meliponini) and their antibiofilm activity on susceptible and multidrug-resistant pathogens: An exploratory analysis.

Biofilms are associated with infections that are resistant to conventional therapies, contributing to the antimicrobial resistance crisis. The need for alternative approaches against biofilms is well-known. Although natural products like stingless bee honeys (tribe: Meliponini) constitute an alternative treatment, much is still unknown. Our main goal was to evaluate the antibiofilm activity of stingless bee honey samples against multidrug-resistant (MDR) pathogens through biomass assays, fluorescence (cell count and viability), and scanning electron (structural composition) microscopy. We analyzed thirty-five honey samples at 15% (v/v) produced by ten different stingless bee species (Cephalotrigona sp., Melipona sp., M. cramptoni, M. fuscopilosa, M. grandis, M. indecisa, M. mimetica, M. nigrifacies, Scaptotrigona problanca, and Tetragonisca angustula) from five provinces of Ecuador (Tungurahua, Pastaza, El Oro, Los Ríos, and Loja) against 24-h biofilms of Staphylococcus aureus, Klebsiella pneumoniae, Candida albicans, and Candida tropicalis. The present honey set belonged to our previous study, where the samples were collected in 2018-2019 and their physicochemical parameters, chemical composition, mineral elements, and minimal inhibitory concentration (MIC) were screened. However, the polyphenolic profile and their antibiofilm activity on susceptible and multidrug-resistant pathogens were still unknown. According to polyphenolic profile of the honey samples, significant differences were observed according to their geographical origin in terms of the qualitative profiles. The five best honey samples (OR24.1, LR34, LO40, LO48, and LO53) belonging to S. problanca, Melipona sp., and M. indecisa were selected for further analysis due to their high biomass reduction values, identification of the stingless bee specimens, and previously reported physicochemical parameters. This subset of honey samples showed a range of 63-80% biofilm inhibition through biomass assays. Fluorescence microscopy (FM) analysis evidenced statistical log reduction in the cell count of honey-treated samples in all pathogens (P <0.05), except for S. aureus ATCC 25923. Concerning cell viability, C. tropicalis, K. pneumoniae ATCC 33495, and K. pneumoniae KPC significantly decreased (P <0.01) by 21.67, 25.69, and 45.62%, respectively. Finally, scanning electron microscopy (SEM) analysis demonstrated structural biofilm disruption through cell morphological parameters (such as area, size, and form). In relation to their polyphenolic profile, medioresinol was only found in the honey of Loja, while scopoletin, kaempferol, and quercetin were only identified in honey of Los Rios, and dihydrocaffeic and dihydroxyphenylacetic acids were only detected in honey of El Oro. All the five honey samples showed dihydrocoumaroylhexose, luteolin, and kaempferol rutinoside. To the authors' best knowledge, this is the first study to analyze stingless bees honey-treated biofilms of susceptible and/or MDR strains of S. aureus, K. pneumoniae, and Candida species.

Biochemical Profile and Antioxidant Properties of Propolis from Northern Spain.

The antioxidant, anti-inflammatory, and antimicrobial characteristics of propolis, a bioactive compound collected from hives, have prompted its use in the food sector in recent times. This study investigated the physicochemical characteristics, phenolic profile, and antioxidant capacity of 31 propolis extracts collected from Northern Spain. The physicochemical composition (resins, waxes, ashes mineral content, and heavy metals) was within the allowable regulatory limits. The analysis of bioactive compounds enabled the identification of 51 constituents: flavonoids (apigenin, catechin, chrysin, quercetin, and pinocembrin) and phenolic acids (caffeic, ferulic, and coumaric). The mean value of total polyphenols was 42.72 ± 13.19 Pinocembrin-Galangin Equivalents/100 g, whereas a range between 1.64 ± 0.04 and 4.95 ± 0.36 Quercetin Equivalents (QE) g/100 g was found for total flavonoids content. The determination of bioactivities revealed significant antioxidant capacity using DPPH (1114.28 ± 10.39 µM Trolox Equivalents and 3487.61 ± 318.66 µM Vitamin C Equivalents). Resin content in propolis samples was positively and significantly correlated with both polyphenols (rho = 0.365; p = 0.043) and flavonoid composition (rho = 0.615; p = 0.000) as well as the antioxidant capacity TEAC DPPH (rho = 0.415; p = 0.020). A multiple regression analysis modeled the correlation between resin composition, flavonoids, and TEAC DPPH values, yielding a significant regression equation (R2 = 0.618; F (2,28) = 22.629; p < 0.000; d = 2.299). Therefore, evaluating physicochemical parameters and biological activities provides a promising framework for predicting propolis' quality and antioxidant properties, thus suggesting its potential as a functional and bioactive compound for the food industry.

The effects of polyphenols against oxidative stress in Caenorhabditis elegans are determined by coexisting bacteria.

Introduction: Increasing evidence supports the role of gut microbiota in many aspects of human health, including immune, metabolic and neurobehavioral traits. Several studies have focused on how different components of the diet, such as polyphenols, can modulate the composition and function of the gut microbiota leading to health benefits. Methods: The effects on the resistance against thermally induced oxidative stress of C. elegans grown in the presence of flavonoids (quercetin or epicatechin) and fed different probiotic strains, namely Lactobacillus plantarum CLC17, Bifidobacterium longum NCIMB 8809 and Enterococcus faecium CECT 410, were explored. Results: Feeding C. elegans with the assayed bacteria in the absence of flavonoids did not significantly affect body size and fertility of the worms neither improve their resistance against oxidative stress compared to E. coli controls. However, increased resistance to stress was found when C. elegans was cultivated in the presence of both L. plantarum and flavonoids, but not with B. longum or E. faecium. An exploratory study revealed the presence of glycosylated and sulfated metabolites together with the aglycone in worms treated with quercetin and fed any of the different assayed LAB strains. However, in the assays with epicatechin a differential metabolite, tentatively identified as 5-(4'-hydroxyphenyl)-γ-valerolactone 3'-O-glucoside, was detected in the worms fed L. plantarum but not with the other bacteria. Conclusion: The obtained results indicated that the interactions bacteria/polyphenol play a key role in the effects produced in C. elegans regarding resistance against oxidative stress, although those effects cannot be only explained by the ability of bacteria to metabolize polyphenols, but other mechanisms should also be involved.

Influence of Altitudes and Development Stages on the Chemical Composition, Antioxidant, and Antimicrobial Capacity of the Wild Andean Blueberry (Vaccinium floribundum Kunth).

The chemical composition and biological capacities of berries depend on environmental parameters, maturity, and location. The Andean blueberry (Vaccinium floribundum Kunth), also known as mortiño, presents a unique combination of several phytochemicals, which play a synergistic role in its characterization as a functional food. We aimed to expose the possible variations that exist in the profile of the phenolic compounds as well as the antioxidant and antimicrobial capacity of the wild Andean blueberry with respect to three ripeness stages and two different altitudes. We found that polyphenols are the predominant compounds in the berry during the early ripeness stage and are the main bioactive compounds that give rise to the antioxidant capacity and inhibition effect on the growth of gram-positive and gram-negative bacteria. Moreover, the accumulation of ascorbic acid, free amino acids, and anthocyanins increases as the ripening process progresses, and they were the main bioactive compounds in the ripe berry. The latter compounds influence the production of the typical bluish or reddish coloration of ripe blueberries. In addition, it was determined that environmental conditions at high altitudes could have a positive influence in all cases. Overall, our data provide evidence regarding the high functional value of the wild Andean blueberry.

Wine, Polyphenols, and Mediterranean Diets. What Else Is There to Say?

A considerable amount of literature has been published claiming the cardiovascular benefits of moderate (red) wine drinking, which has been considered a distinguishing trait of the Mediterranean diet. Indeed, red wine contains relevant amounts of polyphenols, for which evidence of their biological activity and positive health effects are abundant; however, it is also well-known that alcohol, even at a low level of intake, may have severe consequences for health. Among others, it is directly related to a number of non-communicable diseases, like liver cirrhosis or diverse types of cancer. The IARC classifies alcohol as a Group 1 carcinogen, causally associated with the development of cancers of the upper digestive tract and liver, and, with sufficient evidence, can be positively associated with colorectum and female breast cancer. In these circumstances, it is tricky, if not irresponsible, to spread any message on the benefits of moderate wine drinking, about which no actual consensus exists. It should be further considered that other hallmarks of the Mediterranean diet are the richness in virgin olive oil, fruits, grains, and vegetables, which are also good sources of polyphenols and other phytochemicals, and lack the risks of wine. All of these aspects are reviewed in this article.

Combined effects of irradiation and storage time on the nutritional and chemical parameters of dried Agaricus bisporus Portobello mushroom flour.

Portobello variety of Agaricus bisporus mushrooms, appreciated for its taste, makes it desirable to be eaten fresh and also as flour in soups and gravies. Gamma and electron-beam radiation at four doses (1, 2, 5, and 10 kGy) were used to analyze its preservation effect on Portobello mushroom flour. A proximate analysis, as well as the impact on fatty acids, tocopherols, soluble sugars, organic acids, and ergosterol profiles, were performed every 3 months, during a storage period of 1 year. Gamma rays preserved mannitol (most abundant soluble sugar) over the 12 months, while electron beam radiation preserved organic acids. No significant changes were sought for any radiation type, and the slight changes extracted from the estimated marginal means reveal a tendency for irradiation as having preserving effects of nutrients and other important molecules. Thus, both irradiation types, up to 10 kGy are suitable for preservation of A. bisporus Portobello flour.

Caffeic and Dihydrocaffeic Acids Promote Longevity and Increase Stress Resistance in Caenorhabditis elegans by Modulating Expression of Stress-Related Genes.

Caffeic and dihydrocaffeic acid are relevant microbial catabolites, being described as products from the degradation of different phenolic compounds i.e., hydroxycinnamoyl derivatives, anthocyanins or flavonols. Furthermore, caffeic acid is found both in free and esterified forms in many fruits and in high concentrations in coffee. These phenolic acids may be responsible for a part of the bioactivity associated with the intake of phenolic compounds. With the aim of progressing in the knowledge of the health effects and mechanisms of action of dietary phenolics, the model nematode Caenorhabditis elegans has been used to evaluate the influence of caffeic and dihydrocaffeic acids on lifespan and the oxidative stress resistance. The involvement of different genes and transcription factors related to longevity and stress resistance in the response to these phenolic acids has also been explored. Caffeic acid (CA, 200 µM) and dihydrocaffeic acid (DHCA, 300 µM) induced an increase in the survival rate of C. elegans under thermal stress. Both compounds also increased the mean and maximum lifespan of the nematode, compared to untreated worms. In general, treatment with these acids led to a reduction in intracellular ROS concentrations, although not always significant. Results of gene expression studies conducted by RT-qPCR showed that the favorable effects of CA and DHCA on oxidative stress and longevity involve the activation of several genes related to insulin/IGF-1 pathway, such as daf-16, daf-18, hsf-1 and sod-3, as well as a sirtuin gene (sir-2.1).

Influence of Calcium Silicate on the Chemical Properties of Pleurotus ostreatus var. florida (Jacq.) P. Kumm.

Supplementation of mushroom substrates has been linked to a higher resistance against insect pests, although few studies show the impact of this supplementation on the different agronomical parameters of mushrooms or even their chemical composition. In this work, the variation in the biological and chemical composition of oyster mushroom (Pleurotus ostreatus var. florida (Jacq.) P. Kumm) was analysed after varying the substrate supplementation of calcium silicate (0, 0.5, 1, 2, and 4% (w/w%)) during two harvest flushes. Overall, supplementation did not change the weight, the number of fruiting bodies, biological efficiency, yield ratio, and productivity rate of the mushrooms, although the harvest flushes did show significant differences. Furthermore, slight changes were found in the chemical composition with an increase in vitamin D2 and tocopherols for the mushrooms with higher amounts of calcium silicate. Overall, the substrate supplementation did not seem to induce expressive changes or decrease production yields, and can, therefore, continue to be researched as a potential application to fight agronomical pests.

Bioactive compounds, phenolic profile, antioxidant capacity and effectiveness against lipid peroxidation of cell membranes of Mauritia flexuosa L. fruit extracts from three biomes in the Ecuadorian Amazon.

The bioactive compounds, total antioxidant capacity and protective effect against lipid oxidative damage of red blood cell (RBC) membranes of Mauritia flexuosa L. extracts from three altitude levels (low, middle and high zones) were analyzed. The identification of the main polyphenols in the fruit was performed using High Performance Liquid Chromatography/Electrospray Ionization Tandem Mass Spectrometry analysis, while High-Performance Liquid Chromatography - Diode Array Detector was applied for the vitamin C and carotenoid analysis. The ability of the extracts (methanolic, free polyphenols and bound polyphenols) to protect RBC membranes against oxidative destruction was assessed utilizing the thiobarbituric acid reactive substance assay (TBARS) assay. Among the 14 phenolic compounds identified, quercetin glycosides were the most predominant ones. The fruit from the middle altitude zone showed higher vitamin C and lutein contents than those from the low and high areas, whilst higher values of ß-Carotene were obtained in M. flexuosa L. from the low zone. The contents of flavonoids and total polyphenols were lower in fruit from the low zone, whilst the fruit from the middle zone had the highest values. Similar results were observed in the results of the antioxidant capacity assays. However, a significant difference was not found in the protective effect of the extracts from the three altitude zones against lipid peroxidation in RBC membranes.

Baking Optimization as a Strategy to Extend Shelf-Life through the Enhanced Quality and Bioactive Properties of Pulse-Based Snacks.

Food processing optimization can enhance the nutrient bioavailability, storage time, and stability of convenience foods. Baking is a heat and mass transfer process with a high impact on the shelf-life of the obtained product; a small variation in the parameters during baking can lead to significant changes in the end baked product, as it significantly affects the food nutrient profile and bioactive compounds. Response surface methodology (RSM) was used for mapping a response surface over a particular region of interest of baking conditions. The combined effect of the two factors (baking temperature and time) on the selected quality and bioactive parameters as dependent factors was evaluated in order to predict the optimal baking conditions which can facilitate the extended shelf-life of the product through maximizing the antioxidant bioactive properties. This design was used to develop models to predict the effect of the temperature and time baking profile and select those conditions where the quality and bioactive parameters reached a balance to obtain pulse snacks with a high quality, enhanced bioactive properties, and thus a longer shelf-life. Simultaneous optimization by the desirability function showed that a maximum temperature of 210 °C and a time of 14 min were the optimum conditions to produce a pulse-based snack with high antioxidant-antihypertensive activity and nutritional quality.

Caernohabditis elegans as a Model Organism to Evaluate the Antioxidant Effects of Phytochemicals.

The nematode Caernohabditis elegans was introduced as a model organism in biological research by Sydney Brenner in the 1970s. Since then, it has been increasingly used for investigating processes such as ageing, oxidative stress, neurodegeneration, or inflammation, for which there is a high degree of homology between C. elegans and human pathways, so that the worm offers promising possibilities to study mechanisms of action and effects of phytochemicals of foods and plants. In this paper, the genes and pathways regulating oxidative stress in C. elegans are discussed, as well as the methodological approaches used for their evaluation in the worm. In particular, the following aspects are reviewed: the use of stress assays, determination of chemical and biochemical markers (e.g., ROS, carbonylated proteins, lipid peroxides or altered DNA), influence on gene expression and the employment of mutant worm strains, either carrying loss-of-function mutations or fluorescent reporters, such as the GFP.

Protective effect of the medicinal herb infusion "horchata" against oxidative damage in cigarette smokers: An ex vivo study.

Cigarette smoking has been associated with an increase in oxidative stress (OS) and is considered a predisposing factor to chronic noncommunicable diseases, whilst dietary antioxidants has been proposed as an alternative to cope with this oxidative stress. In this study, 20 smokers and 20 non-smokers were studied with the aim of determining their antioxidant status, as well as the ability of an infusion of 23 medicinal plants, to counteract the damage caused by OS. The plasma, red blood cells (RBCs) and polymorphonuclear cells (PBMCs) of both groups were incubated or not with the horchata infusion extract and then the OS markers, genotoxicity, nanostructure of RBCs membrane and genes related to oxidative responses and cellular functionality were evaluated. Up to 33 different compounds, mainly quercetin glycosides, were identified in the extract. A significant deterioration in the antioxidant status in smokers compared to non-smokers was found. The horchata infusion extract improved the nanostructure of RBCs and DNA damage, as well as the activity of the endogenous antioxidant enzymes and markers of oxidative damage to lipid, and proteins in plasma, RBCs and PBMCs in both groups, whilst no significant changes were found in the expression of different genes related to OS response.

Assessment of the In Vivo Antioxidant Activity of an Anthocyanin-Rich Bilberry Extract Using the Caenorhabditis elegans Model.

Anthocyanins have been associated with several health benefits, although the responsible mechanisms are not well established yet. In the present study, an anthocyanin-rich extract from bilberry (Vaccinium myrtillus L.) was tested in order to evaluate its capacity to modulate reactive oxygen species (ROS) production and resistance to thermally induced oxidative stress, using the nematode Caenorhabditis elegans as an in vivo model. The assays were carried out with the wild-type N2 strain and the mutant strains daf-16(mu86) I and hsf-1(sy441), which were grown in the presence of two anthocyanin extract concentrations (5 and 10 µg/mL in the culture medium) and further subjected to thermal stress. The treatment with the anthocyanin extract at 5 µg/mL showed protective effects on the accumulation of ROS and increased thermal resistance in C. elegans, both in stressed and non-stressed young and aged worms. However, detrimental effects were observed in nematodes treated with 10 µg/mL, leading to a higher worm mortality rate compared to controls, which was interpreted as a hormetic response. These findings suggested that the effects of the bilberry extract on C. elegans might not rely on its direct antioxidant capacity, but other mechanisms could also be involved. Additional assays were performed in two mutant strains with loss-of-function for DAF-16 (abnormal DAuer Formation factor 16) and HSF-1 (Heat Shock Factor 1) transcription factors, which act downstream of the insulin/insulin like growth factor-1 (IGF-1) signaling pathway. The results indicated that the modulation of these factors could be behind the improvement in the resistance against thermal stress produced by bilberry anthocyanins in young individuals, whereas they do not totally explain the effects produced in worms in the post-reproductive development stage. Further experiments are needed to continue uncovering the mechanisms behind the biological effects of anthocyanins in living organisms, as well as to establish whether they fall within the hormesis concept.

Current and future experimental approaches in the study of grape and wine polyphenols interacting gut microbiota.

Interactions between polyphenols and gut microbiota are indeed a major issue of current interest in food science research. Knowledge in this subject is progressing as the experimental procedures and analysis techniques do. The aim of this article is to critically review the more leading-edge approaches that have been applied so far in the study of the interactions between grape/wine polyphenols and gut microbiota. This is the case of in vitro dynamic gastrointestinal simulation models that try to mitigate the limitations of simple static models (batch culture fermentations). More complex approaches include the experimentation with animals (mice, rats, pigs, lambs and chicks) and nutritional intervention studies in humans. Main advantages and limitations as well as the most relevant findings achieved by each approach in the study of how grape/wine polyphenols can modulate the composition and/or functionality of gut microbiota, are detailed. Also, common findings obtained by the three approaches (in vitro, animal models and human nutritional interventions) such as the fact that the Firmicutes/Bacteroidetes ratio tends to decrease after the feed/intake/consumption of grape/wine polyphenols are highlighted. Additionally, a nematode (Caenorhabditis elegans) model, previously used for investigating the mechanisms of processes such as aging, neurodegeneration, oxidative stress and inflammation, is presented as an emerging approach for the study of polyphenols interacting gut microbiota. © 2020 Society of Chemical Industry.

Pechiche (Vitex Cymosa Berteo ex Speng), a Nontraditional Fruit from Ecuador, is a Dietary Source of Phenolic Acids and Nutrient Minerals, in Addition to Efficiently Counteracting the Oxidative-Induced Damage in Human Dermal Fibroblasts.

Pechiche fruits (Vitex cymosa Berteo ex Speng) from Ecuador were studied to determine their phenolic acid profile, nutrient minerals and capacity to protect primary human dermal fibroblasts (HDFa) against oxidative-induced damage. Up to five phenolic acids were identified, with homovanillic acid as the main one. Vitamin C, ß-carotene and lutein were also determined. Phosphorus and potassium were the main macrominerals, while iron was the principal micromineral. HDFa were preincubated with a crude pechiche extract (PCext) and then subjected to oxidative stress. The activity of five antioxidant enzymes, intracellular reactive oxygen species (ROS) and ATP levels and lipid peroxidation and protein oxidation were used as markers of oxidative damage. Preincubation with PCext for 24 h allowed for the significant reduction of intracellular ROS levels, improved the intracellular ATP levels and protected lipids and proteins against oxidative damage (p 0.05). Additionally, preincubation with PCext was also able to significantly (p < 0.05) improve the activity of the antioxidant enzymes catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and glutathione transferase, compared to the stressed group without pretreatment. The results obtained in this study suggest the potential of pechiche as a source of bioactive compounds, as well as its beneficial effect against oxidative stress.

Exploring Target Genes Involved in the Effect of Quercetin on the Response to Oxidative Stress in Caenorhabditis elegans.

Quercetin is one the most abundant flavonoids in the human diet. Although it is well known that quercetin exhibits a range of biological activities, the mechanisms behind these activities remain unresolved. The aim of this work is to progress in the knowledge of the molecular mechanisms involved in the biological effects of quercetin using Caenorhabditis elegans as a model organism. With this aim, the nematode has been used to explore the ability of this flavonoid to modulate the insulin/insulin-like growth factor 1(IGF-1) signaling pathway (IIS) and the expression of some genes related to stress response. Different methodological approaches have been used, i.e., assays in knockout mutant worms, gene expression assessment by RT-qPCR, and C. elegans transgenic strains expressing green fluorescent protein (GFP) reporters. The results showed that the improvement of the oxidative stress resistance of C. elegans induced by quercetin could be explained, at least in part, by the modulation of the insulin signaling pathway, involving genes age-1, akt-1, akt-2, daf-18, sgk-1, daf-2, and skn-1. However, this effect could be independent of the transcription factors DAF-16 and HSF-1 that regulate this pathway. Moreover, quercetin was also able to increase expression of hsp-16.2 in aged worms. This observation could be of particular interest to explain the effects of enhanced lifespan and greater resistance to stress induced by quercetin in C. elegans, since the expression of many heat shock proteins diminishes in aging worms.

A comparative study between conventional and non-conventional extraction techniques for the recovery of ergosterol from Agaricus blazei Murrill.

Response surface methodology was applied to optimize the recovery of ergosterol from an agroindustrial residue of Agaricus blazei Murrill, by comparing conventional (heat-assisted extraction, HAE) and more sustainable non-conventional approaches (ultrasound and microwave-assisted extractions, UAE and MAE, respectively). A circumscribed central composite design was employed to optimize and describe the interactive effects among variables of the HAE, MAE (time and temperature) and UAE systems (time and ultrasound power), and their performances compared with the standard soxhlet extraction system. The optimum conditions were predicted as 150 min, 81.6 °C for HAE, 30 min, 400 W for UAE, and 25 min, 134.6 °C, for the MAE system. The UAE system was identified as the most appropriate technique to obtain extracts with the highest amount of ergosterol, followed by MAE and HAE. Overall, these results demonstrate the potential of using the fruiting bodies of A. blazei as a suitable source to obtain ergosterol-rich extracts, which can be used as an ingredient for various bio-based industrial applications.

Flour fortification for nutritional and health improvement: A review.

Deficiencies of micronutrients, essentially vitamins and minerals, have mainly cause several illnesses, especially in children and women worldwide. Governments and world organizations have focused great efforts to address these shortcomings and improve the health of the populations. This malnutrition can be combated by fortifying basic foods that are consumed daily. Thus, flours, especially wheat, maize and rice, are a popular and common food in the world's populations diet and are gaining considerable attention as a suitable vehicle for micronutrient fortification. There are some studies that show the effectiveness of flour fortification in combating micronutrient deficiencies and several diseases and the flour fortification strategies are directed to meet nutritional and health needs of the populations. The main points discussed in this review are food fortification, with great focus in flour fortification, health benefits, and legislative issues. This review also highlights multifaceted issues related to flour fortification to meet nutritional needs and to improve the health of vulnerable populations.

Nutritional properties, identification of phenolic compounds, and enzyme inhibitory activities of Feijoa sellowiana leaves.

The nutritional values, the identification of individual phenolic compounds as well as the functional properties (in vitro acetylcholinesterase (AChE) and pancreatic lipase inhibition) of Tunisian Feijoa sellowiana (O.Berg) leaves were determined by high-performance liquid chromatography coupled with diode array and mass spectrometry detector. Feijoa Sellowiana  leaves Extract (FSLE) were evaluated in the present work. Macronutrient components (proteins, carbohydrates, dietary fiber, lipids, and ashes) of FSLE as well as their fatty acids and mineral content were determined. The individual phenolic composition was characterized by the presence of flavonols (mostly quercetin glycosides), flavan-3-ols (procyanidins and catechins), and phenolic acid derivatives. To understand the possible inhibition mechanism exerted by the extract components, enzyme kinetic studies using derived Lineweaver-Burk (LB) plots and Michaelis-Menten were performed. The obtained results evidenced that FSLE exhibited important AChE inhibitory effect, behaving as a noncompetitive inhibitor. Furthermore, the leaves' extract inhibited irreversibly the pancreatic lipase, with maximum inhibition (70%) achieved at 1 mg/ml. PRACTICAL APPLICATIONS: In many countries of the world, Feijoa Sellowiana leaves are used as an alternative to tea drinks and as a folkloric medicine. Moreover, it is well known that the phytochemical compounds are a practical alternative for the prevention of many chronic diseases such as Alzheimer's and obesity. For this reason, the present study aimed to evaluate the nutritional, individual phenolic compounds, and functional properties of Feijoa Sellowiana leaves to valorize them as a food and pharmaceutical bioactive human source.