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OBJECTIVE: This study aims to characterize in vitro D-chiro-inositol intestinal absorption and identify factors able to improve its bioavailability. D-chiro-inositol, one of the natural occurring stereoisomer of myo-inositol, acts as a second messenger in insulin-regulated glucose metabolism in complementary mode with myo-inositol. Because of their insulin-mimetic activities and safety, both myo-inositol and D-chiro-inositol are often employed as supplements in insulin-resistance treatment. MATERIALS AND METHODS: Trans-epithelial passage of D-chiro-inositol was evaluated in the human intestinal Caco-2 cell line differentiated on filter, a widely established in vitro model to study intestinal absorption. D-chiro-inositol transport was assayed in a concentration range corresponding to an estimated in vivo concentration following oral supplementation. α-Lactalbumin peptides, obtained by in vitro simulated gastrointestinal digestion, were tested as possible modulators of the intestinal permeability of D-chiro-inositol. RESULTS: The absorption of this stereoisomer was relatively low and presumably due to passive diffusion, while it was greatly enhanced by the presence of α-Lactalbumin digest. α-Lactalbumin peptides induced an increase in paracellular permeability that was completely reversible, indicating lack of cytotoxicity. This effect involved temporary rearrangement of F-actin apical cytoskeleton and of the tight junction protein ZO-1. CONCLUSIONS: Although further studies are required to identify and characterize the most effective peptides, the ability of α-Lactalbumin digest to act as absorption enhancers may have very interesting and promising applications in the fields of nutritional supplements and pharmacology. [ABSTRACT FROM AUTHOR]

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

This paper reviews the current knowledge regarding modifications to chlorophylls during the processing of green table olives treated with alkali. Particular attention is given to the pheophytinization reactions (substitution of Mg 2+ by 2H + in the chlorophyll chromophore group) that can take place because of pH and/or temperature changes and the possible sequential substitution of the 2H + with Cu 2+ within the chlorophyll porphyrin ring. These reactions may have a direct impact on the commercial value of olive productions as some naturally forming Cu-chlorophylls complexes (i) are identical to strictly forbidden colorants for table olives (E141) and (ii) have been identified as responsible for the unwelcome appearance of the so-called green staining alteration (characterized by bluish-green zones distributed over the olive skin of the drupes).

Chlorophyll pigments are thought to be responsible for the highly appreciated green color of unfermented Castelvetrano-style table olives, but no studies have considered the effects of a controlled addition of copper during storage or packaging at the industrial level. For this purpose, chlorophyll derivatives were analyzed in Nocellara cultivar table olives debittered industrially using the Castelvetrano method, via means of HPLC and MS analyses, following the addition of copper in alkaline brines stored at 4 °C for 3 months in 220 L barrels, and during the subsequent storage in acid brines in commercial 400 g packages at 4 °C for up to 18 months. The presence of copper in storage or in packaging brines both contributed significantly to maintaining the green color of the olives, which was associated with a specific pattern of chlorophyll derivatives, as evidenced by principal component analysis. Notably, re-greening was rapidly achievable also for olives that had yellowed for 18 months at a copper concentration below the limit of EU legislation. Finally, by means of PCA, we also demonstrated that a short-term thermic treatment can work as an accelerated predictive tool in determining the fate of chlorophyll derivatives.

Hamamelis virginiana L. a rich source of both condensed and hydrolyzable tannins, utilized to treat dermatological disorders. Since no experimental and clinical data is available for its use as oral formulation in skin related disorders, the purpose of this study was to investigate the effects of Hamaforton™ ( Hamamelis virginiana extract) metabolites on gene dysregulation induced by ultraviolet A radiation in cultured human dermal fibroblasts. A combination of in vivo and ex vivo experimental designs has been exploited in order to take into account the polyphenol metabolic transformation that occurs in humans. 12 healthy volunteers received either a capsule of Hamaforton™ or a placebo in a randomized, blinded crossover trial. After Hamaforton™ ingestion, the kinetic of appearance of galloyl derivatives was measured in plasma. Then, in the ex vivo experiment, the serum isolated after supplementation was used as a source of Hamaforton™ metabolites to enrich the culture medium of dermal fibroblasts exposed to ultraviolet A radiation. Three different gallic acid metabolites (4-O-methyl gallic acid, 4-O-methyl gallic acid sulphate and trimethyl gallic acid glucuronide) were identified in volunteer plasma. While, ultraviolet A irradiation of dermal fibroblasts affected the expression of extracellular matrix genes, the presence of Hamaforton™ metabolites in the culture media did not affect the expression of most of those genes. However, the activation of the expression of 10 different genes involved in repair processes for the maintenance of skin integrity, suggest that the metabolites can play a role in damage recovery. To our knowledge, this is the first study that demonstrates the bioavailability of Hamaforton™ phenolic compounds, and the effects of its metabolites on cultured dermal fibroblast response to ultraviolet A irradiation., Competing Interests: CB is an employee of Horphag Research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Natella, Guantario, Ambra, Ranaldi, Intorre, Burki and Canali.)

Background and Aim: During Coronavirus disease 2019 (Covid-19) Italy experienced deep lockdown with closure of almost all activities, with the exception for food shops and few others. During this quarantine, alteration of dietary habits occurred, due to the changes in food availability and mandatory meal house-consumption. The change in dietary habits could somehow be directed by freely accessible information available on internet.  Thus, s we evaluated the type and the scientific quality of the information provided to the Italian population by the most visible web sites found on google, relating diet in Covid-19 time., Methods: we systematically perform a reliability and content analysis of Italian language websites using google as search engine and a combinations of diet/nutrition/Covid-19 as search terms Results: 88 webpages were included in the study, the great part representing newspaper webpages. Institutional webpages, despite having high scientific quality, did not have high visibility. Generally, all the other webpages reported information of medium-quality scientific level., Conclusion: finding appropriate solutions to redirect the population's attention to more reliable and accessible information is mandatory.

Purpose: Validated biomarkers of food intake (BFIs) have recently been suggested as a useful tool to assess adherence to dietary guidelines or compliance in human dietary interventions. Although many new candidate biomarkers have emerged in the last decades for different foods from metabolic profiling studies, the number of comprehensively validated biomarkers of food intake is limited. Apples are among the most frequently consumed fruits and a rich source of polyphenols and fibers, an important mediator for their health-protective properties., Methods: Using an untargeted metabolomics approach, we aimed to identify biomarkers of long-term apple intake and explore how apples impact on the human plasma and urine metabolite profiles. Forty mildly hypercholesterolemic volunteers consumed two whole apples or a sugar and energy-matched control beverage, daily for 8 weeks in a randomized, controlled, crossover intervention study. The metabolome in plasma and urine samples was analyzed via untargeted metabolomics., Results: We found 61 urine and 9 plasma metabolites being statistically significant after the whole apple intake compared to the control beverage, including several polyphenol metabolites that could be used as BFIs. Furthermore, we identified several endogenous indole and phenylacetyl-glutamine microbial metabolites significantly increasing in urine after apple consumption. The multiomic dataset allowed exploration of the correlations between metabolites modulated significantly by the dietary intervention and fecal microbiota species at genus level, showing interesting interactions between Granulicatella genus and phenyl-acetic acid metabolites. Phloretin glucuronide and phloretin glucuronide sulfate appeared promising biomarkers of apple intake; however, robustness, reliability and stability data are needed for full BFI validation., Conclusion: The identified apple BFIs can be used in future studies to assess compliance and to explore their health effects after apple intake. Moreover, the identification of polyphenol microbial metabolites suggests that apple consumption mediates significant gut microbial metabolic activity which should be further explored.

Objectives: Uncontrolled ingestion of alcohol has dramatic consequences on the entire organism that are also associated with the oxidation process induced by alcohol and elevate radical oxygen species. Resveratrol, a nonflavonoid phenol, shows well-documented antioxidant properties. We investigated the potential antioxidant ability of this natural compound in a mouse model of alcohol addiction., Methods: We administered (per os) for 60 d 10 mg · kg -1 · d -1 of resveratrol in alcoholic adult male mice. Oxidative stress was evaluated by measuring serum-free oxygen radicals defense and free oxygen radical levels. Resveratrol metabolites were measured in the serum of mice that were administered with resveratrol. Finally, the effect of resveratrol on the alcohol-induced alteration of brain-derived neurotrophic factors (BDNF) in the liver was investigated., Results: Prolonged consumption of resveratrol strongly counteracts serum radical oxygen species formation caused by chronic alcohol intake without effects on natural, free oxygen radical defense. The presence of resveratrol metabolites in the serum only of animals supplemented with resveratrol potentiates the evidence that the antioxidant effect observed is due to the ingestion of the natural compound. Moreover, resveratrol supplementation can counteract alcohol-induced BDNF elevation in the liver, which is the main target of organ alcohol-induced damage., Conclusions: The consumption of resveratrol through metabolite formation may play a protective role by decreasing free radical formation and modulating the BDNF involved in hepatic disruption induced by chronic alcohol consumption. Further investigation into the mechanism underlying the protective effect could reinforce the potential use of resveratrol as a dietary supplement to prevent damage associated with chronic alcohol abuse., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Several studies highlighted a correlation between folic acid deficiency and high plasma homocysteine concentration, considered a risk factor for multifactorial diseases. Natural folates represent an emerging alternative strategy to supplementation with synthetic folic acid, whose effects are controversial. The present work was, therefore, performed in hyperhomocysteinemic mice to study the impact of supplementation with dairy matrices containing natural folates on plasma homocysteine levels and faecal microbiota composition., Methods: Forty mice were divided into six groups, two of which fed control or folic acid deficient (FD) diets for 10 weeks. The remaining four groups were fed FD diet for the first 5 weeks and then shifted to a standard control diet containing synthetic folic acid (R) or a FD diet supplemented with folate-enriched fermented milk (FFM) produced by selected lactic acid bacteria, fermented milk (FM), or milk (M), for additional 5 weeks., Results: Supplementation with dairy matrices restored homocysteine levels in FD mice, although impacting differently on hepatic S-adenosyl-methionine levels. In particular, FFM restored both homocysteine and S-adenosyl-methionine levels to the control conditions, in comparison with FM and M. Next generation sequencing analysis revealed that faecal microbiota of mice supplemented with FFM, FM and M were characterised by a higher richness of bacterial species in comparison with C, FD and R groups. Analysis of beta diversity highlighted that the three dairy matrices determined specific, significant variations of faecal microbiota composition, while hyperhomocysteinemia was not associated with significant changes., Conclusions: Overall, the results represent a promising starting point for the applicability of food matrices enriched in natural folates to manage hyperhomocysteinemia.

Fungal contamination poses at risk the whole food production chain - from farm to fork - with potential negative impact on human health. So far, the insurgence of pathogens has been restrained by the use of chemical compounds, whose residues have gradually accumulated determining toxic effects in the environment. Modern innovative techniques imply the use of natural and eco-sustainable bioactive plant molecules as pathogens and pests-control agents. These may be profitably recovered in large amounts at the end of industrial milling processes. This is the case of the non-digestible hull of common buckwheat ( Fagopyrum esculentum Moench), a natural source of polyphenols, tocopherols, phytosterols and fatty acids. We extract these compounds from the hull of buckwheat; apply them to Aspergillus flavus - aflatoxin producer - under in vitro conditions, checking their ability to inhibit fungal growth and aflatoxin biosynthesis. Moreover, a solvent free method implying the adoption of supercritical CO 2 as solvent was set up to extract lipophilic molecules from the buckwheat' hulls. Positive results in controlling fungal growth and aflatoxin biosynthesis let infer that the extracts could be further tested also under in vivo conditions.

Broccoli sprouts are considered functional food as they are naturally enriched in glucoraphanin (GR) that is the biological precursor of the anticancer compound sulforaphane (SFN). Due to its health promoting value, also broccoli sprout juice is becoming very popular. The present study aimed to quantitatively assess the conversion of GR to its hydrolysis products, SFN and SFN-nitrile, during the juice preparation process. We demonstrated that SFN plus SFN-nitrile yield from glucoraphanin is quite low (≈25%) and that some SFN is lost during the juice preparation partially due to the spontaneous conversion to sulforaphane-amine or conjugation to GSH and proteins naturally present in the juice. Our results demonstrate that the detection of the sole SFN free form does not provide reliable information about the real concentration of this functional compound in the juice., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Apples are one of the most commonly consumed fruits and their high polyphenol content is considered one of the most important determinants of their health-promoting activities. Here we studied the nutrikinetics of apple polyphenols by UHPLC-HRMS metabolite fingerprinting, comparing bioavailability when consumed in a natural or a polyphenol-enriched cloudy apple juice. Twelve men and women participated in an acute single blind controlled crossover study in which they consumed 250 mL of cloudy apple juice (CAJ), Crispy Pink apple variety, or 250 mL of the same juice enriched with 750 mg of an apple polyphenol extract (PAJ). Plasma and whole blood were collected at time 0, 1, 2, 3 and 5 h. Urine was collected at time 0 and 0-2, 2-5, 5-8, and 8-24 h after juice consumption. Faecal samples were collected from each individual during the study for 16S rRNA gene profiling. As many as 110 metabolites were significantly elevated following intake of polyphenol enriched cloudy apple juice, with large inter-individual variations. The comparison of the average area under the curve of circulating metabolites in plasma and in urine of volunteers consuming either the CAJ or the PAJ demonstrated a stable metabotype, suggesting that an increase in polyphenol concentration in fruit does not limit their bioavailability upon ingestion. Faecal bacteria were correlated with specific microbial catabolites derived from apple polyphenols. Human metabolism of apple polyphenols is a co-metabolic process between human encoded activities and those of our resident microbiota. Here we have identified specific blood and urine metabolic biomarkers of apple polyphenol intake and identified putative associations with specific genera of faecal bacteria, associations which now need confirmation in specifically designed mechanistic studies., (Copyright © 2018. Published by Elsevier Ltd.)

A multi-methodological approach was applied to study red sweet peppers (Capsicum annuum L.) ecotype "Cornetto di Pontecorvo" grown in a greenhouse or in open field. This approach includes morphological analysis, chemical composition determination, and biological activity evaluation of different extracts from pepper fruits. Untargeted analyses, namely NMR spectroscopy and mass spectrometry, allowed the comprehensive pepper metabolite profile of pepper pulp, peel and seeds hydroalcoholic and organic extracts to be determined, showing the presence of sugars, organic acids, amino acids and other secondary metabolites. Targeted analyses, such as HPLC-PDA, HPLC-TLC and spectrophotometric analyses allowed polyphenols, tannins, flavonoids and pigments content to be determined. Samples quality and freshness were verified by the low content of biogenic amines and mycotoxins, as determined using HPLC-FLD and HPLC-MS, respectively. Preliminary biological results demonstrated the ability of the organic extracts to inhibit α-amylase, a key enzyme in the control of glucose metabolism., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Fatty acids and bioactive lipophilic and hydrophilic compounds (tocopherols, β-carotene, lutein, squalene, total polyphenols and secoiridoids) in monocultivar Italian extra-virgin olive oil (EVOO) samples produced from the Leccino cultivar and six other yet uncharacterised cultivars (Rustica, Carpinetana, Dritta, Gentile di Chieti and Intosso) were analysed, also taking into account the effect of the type of decanter used for the oil extraction. Significant differences among cultivars were found for α-tocopherol and squalene, but not for carotenoids. Among phenols, cultivars significantly influenced oleuropein and ligstroside aglycones contents, but not those of the dialdehydic form of decarboxymethyl elenolic acid linked neither to tyrosol nor hydroxytyrosol. As previously reported, phenol is quantitatively affected by the type of decanter used for oil extraction. Accordingly, we found that the two-phases decanter preserved in the oil 1.5 times more phenolic compounds as compared with three-phases, whereas it did not influence the amount of lipophilic compounds. Moreover, our data statistically support the finding that type of decanter affects phenols also qualitatively. In fact, the two-phases decanter preferably preserved more the hydroxytyrosol secoiridoid derivatives than the tyrosol ones. Our results from one hand characterise for the first time oils previously unreported, from the other give some new indications on the relative role of factors relevant for the achievement of biologically active extra-virgin oil, i.e. the cultivar and technological ones.

Nutrigenomics data on the functional components of olive oil are still sparse, but rapidly increasing. Olive oil is the main source of fat and health-promoting component of the Mediterranean diet. Positive effects have been observed on genes involved in the pathobiology of most prevalent age- and lifestyle-related human conditions, such as cancer, cardiovascular disease and neurodegeneration. Other effects on health-promoting genes have been identified for bioactive components of olives and olive leafs. Omics technologies are offering unique opportunities to identify nutritional and health biomarkers associated with these gene responses, the use of which in personalized and even predictive protocols of investigation, is a main breakthrough in modern medicine and nutrition. Gene regulation properties of the functional components of olive oil, such as oleic acid, biophenols and vitamin E, point to a role for these molecules as natural homeostatic and even hormetic factors with applications as prevention agents in conditions of premature and pathologic aging. Therapeutic applications can be foreseen in conditions of chronic inflammation, and particularly in cancer, which will be discussed in detail in this review paper as major clinical target of nutritional interventions with olive oil and its functional components. © 2016 BioFactors, 43(1):17-41, 2017., (© 2016 International Union of Biochemistry and Molecular Biology.)