Phenolic Composition of Red and White Wine Byproducts from Different Grapevine Cultivars from La Rioja (Spain) and How This Is Affected by the Winemaking Process.

The recovery of raw materials offers an opportunity for applying the principles of circular bioeconomy. The phenolic composition of three underused wine byproducts (skin, seed, and bunch stem) was analyzed through UHPLC-QqQ-MS/MS to evaluate the intercultivar variability comparing red and white grape cultivars from La Rioja (Spain) and the influence of the winemaking, comparing conventional fermentation and carbonic maceration. We observed that the red skin, especially from Graciano, is rich in anthocyanins, whereas the white skin contains mainly phenolic acids, flavonols, and flavan-3-ols, with Maturana Blanca being the richest variety. Seeds are rich in flavan-3-ols and lignans with Maturana Blanca and Viura, respectively, the richest cultivars. Stems contain high amounts of flavan-3-ols, lignans, and stilbenes, with the red cultivars of Garnacha and Tempranillo being the richest samples. Carbonic maceration has a negative effect on the phenolic amount compared to conventional fermentation. In synthesis, we observed that each type of byproduct from red or white grape cultivars has a particular phenolic composition that can result in obtaining different ingredients with particular phenolic composition for target applications.

Urinary excretion of organosulfur compounds after acute ingestion of black onion.

Onion (Allium cepa L.) and its newly derived product "black onion" are characterised by the presence of compounds with potential bioactivity, particularly organosulfur compounds (OSCs). However, little is known about the metabolism, distribution, and excretion of these compounds as they pass through the gastrointestinal tract. This study monitored healthy subjects after an acute intake of black onion and analysed the excretion of OSCs using UHPLC-HRMS. A total of 31 OSCs were detected in urine after the acute ingestion of black onion, the main components being S-methyl-L-cysteine sulfoxide (methiin) (13.6 ± 3.9 µmol), isoalliin (12.4 ± 4.7 µmol) and S-propyl-L-cysteine (deoxypropiin) (3.1 ± 0.7 µmol). Moreover, N-acetylated metabolites of the major OSCs detected in black onion, namely, N-acetyl-S-(1-propenyl)-L-cysteine sulfoxide (NAS1PCS) and N-acetyl-S-(1-propenyl)-L-cysteine (NAS1PC), were found in urine after black onion consumption. The N-acetylation reaction takes place in the kidneys and liver, and metabolism pathways are proposed to explain the excretion of OSCs in urine. The basis of the identification of OSCs as urinary metabolites after black onion consumption is described for the first time and provides the basis for further research.

Bioavailability of Organosulfur Compounds after the Ingestion of Black Garlic by Healthy Humans.

The consumption of black garlic has been related to a decreased risk of many human diseases due to the presence of phytochemicals such as organosulfur compounds (OSCs). However, information on the metabolization of these compounds in humans is limited. By means of ultra-high-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS), this study aims to determine the OSCs and their metabolites excreted in urine 24 h after an acute intake of 20 g of black garlic by healthy humans. Thirty-three OSCs were identified and quantified, methiin (17,954 ± 6040 nmol), isoalliin (15,001 ± 9241 nmol), S-(2-carboxypropyl)-L-cysteine (8804 ± 7220 nmol) and S-propyl-L-cysteine (deoxypropiin) (7035 ± 1392 nmol) being the main ones. Also detected were the metabolites N-acetyl-S-allyl-L-cysteine (NASAC), N-acetyl-S-allyl-L-cysteine sulfoxide (NASACS) and N-acetyl-S-(2-carboxypropyl)-L-cysteine (NACPC), derived from S-allyl-L-cysteine (SAC), alliin and S-(2-carboxypropyl)-L-cysteine, respectively. These compounds are potentially N-acetylated in the liver and kidney. The total excretion of OSCs 24 h after the ingestion of black garlic was 64,312 ± 26,584 nmol. A tentative metabolic pathway has been proposed for OSCs in humans.

Impact of Phenol-Enriched Olive Oils on Serum Metabonome and Its Relationship with Cardiometabolic Parameters: A Randomized, Double-Blind, Cross-Over, Controlled Trial.

Phenol-rich foods consumption such as virgin olive oil (VOO) has been shown to have beneficial effects on cardiovascular diseases. The broader biochemical impact of VOO and phenol-enriched OOs remains, however, unclear. A randomized, double-blind, cross-over, controlled trial was performed with thirty-three hypercholesterolemic individuals who ingested for 3-weeks (25 mL/day): (1) an OO enriched with its own olive oil phenolic compounds (PCs) (500 ppm; FOO); (2) an OO enriched with its own olive oil PCs (250 ppm) plus thyme PCs (250 ppm; FOOT); and (3) a VOO with low phenolic content (80 ppm). Serum lipid and glycemic profiles, serum 1H-NMR spectroscopy-based metabolomics, endothelial function, blood pressure, and cardiovascular risk were measured. We combined OPLS-DA with machine learning modelling to identify metabolites discrimination of the treatment groups. Both phenol-enriched OO interventions decreased the levels of glutamine, creatinine, creatine, dimethylamine, and histidine in comparison to VOO one. In addition, FOOT decreased the plasma levels of glycine and DMSO2 compared to VOO, while FOO decreased the circulating alanine concentrations but increased the plasma levels of acetone and 3-HB compared to VOO. Based on these findings, phenol-enriched OOs were shown to result in a favorable shift in the circulating metabolic phenotype, inducing a reduction in metabolites associated with cardiometabolic diseases.

Artificial intelligence to estimate wine volume from single-view images.

In this paper, we present a method to determine the volume of wine in different types of glass liquid containers from a single-view image. The proposed model predicts red wine volume from a photograph of the glass containing the wine. Experimental results demonstrated satisfactory performance of our image-based wine measurement system, with a Mean Absolute Error lower than 10 mL . To train and evaluate our system, we introduced the WineGut_BrainUp dataset, a new dataset of glasses of wine that contains 24305 laboratory images, including a wide range of containers, volumes of wine, backgrounds, object distances, angles and lightning, with or without calibration object. The proposed methodology is a suitable analytical tool for automate measurement of red wine volume. Indeed, it has potential real life applications in diet monitoring and wine consumption studies.

New red-fleshed apple cultivars: a comprehensive review of processing effects, (poly)phenol bioavailability and biological effects.

Red-fleshed apple cultivars with an enhanced content of anthocyanins have recently attracted the interest of apple producers and consumers due to their attractive color and promising added health benefits. In this paper, we provide the first comprehensive overview of new hybrid red-fleshed apples, mainly focusing on their (poly)phenolic composition, the effect of processing, the (poly)phenolic bioavailability and the biological effects. Evidence so far from in vitro and in vivo studies supports their added beneficial effects compared to common apples on health outcomes such as cancer, cardiovascular disease, inflammation and immune function, which are mainly related to their specific (poly)phenol composition.

Red-Fleshed Apples Rich in Anthocyanins and White-Fleshed Apples Modulate the Aorta and Heart Proteome in Hypercholesterolaemic Rats: The AppleCOR Study.

The impact of a red-fleshed apple (RFA) rich in anthocyanins (ACNs), a white-fleshed apple (WFA) without ACNs, and an extract infusion from Aronia fruit (AI) equivalent in dose of cyanidin-3-O-galactoside (main ACN) as RFA was determined by the proteome profile of aorta and heart as key cardiovascular tissues. Hypercholesterolaemic Wistar rats were separated into six groups (n = 6/group; three males and three females) and the proteomic profiles were analyzed using nanoliquid chromatography coupled to mass spectrometry. No adverse events were reported and all products were well tolerated. RFA downregulated C1QB and CFP in aorta and CRP in heart. WFA downregulated C1QB and CFP in aorta and C9 and C3 in aorta and heart, among other proteins. AI downregulated PRKACA, IQGAP1, and HSP90AB1 related to cellular signaling. Thus, both apples showed an anti-inflammatory effect through the complement system, while RFA reduced CRP. Regardless of the ACN content, an apple matrix effect was observed that involved different bioactive components, and inflammatory proteins were reduced.

Functional implications of bound phenolic compounds and phenolics-food interaction: A review.

Sizeable scientific evidence indicates the health benefits related to phenolic compounds and dietary fiber. Various phenolic compounds-rich foods or ingredients are also rich in dietary fiber, and these two health components may interrelate via noncovalent (reversible) and covalent (mostly irreversible) interactions. Notwithstanding, these interactions are responsible for the carrier effect ascribed to fiber toward the digestive system and can modulate the bioaccessibility of phenolics, thus shaping health-promoting effects in vivo. On this basis, the present review focuses on the nature, occurrence, and implications of the interactions between phenolics and food components. Covalent and noncovalent interactions are presented, their occurrence discussed, and the effect of food processing introduced. Once reaching the large intestine, fiber-bound phenolics undergo an intense transformation by the microbial community therein, encompassing reactions such as deglycosylation, dehydroxylation, α- and ß-oxidation, dehydrogenation, demethylation, decarboxylation, C-ring fission, and cleavage to lower molecular weight phenolics. Comparatively less information is still available on the consequences on gut microbiota. So far, the very most of the information on the ability of bound phenolics to modulate gut microbiota relates to in vitro models and single strains in culture medium. Despite offering promising information, such models provide limited information about the effect on gut microbes, and future research is deemed in this field.

Chemopreventive effects of anthocyanins on colorectal and breast cancer: A review.

The present review has analyzed the scientific literature, available in the PubMed and Scopus databases, in order to summarize the current state of diet anthocyanin research in breast cancer (BC) and colorectal cancer (CRC) animal models but also for up-to-date human studies. For CRC, 28 preclinical and 9 clinical studies were selected in line with our search query in science databases. In relation to BC, 14 preclinical and 5 clinical studies were selected. Remarkably, all the preclinical studies, to a greater or lesser degree, suggested a chemoprevention effect of anthocyanin in BC/CRC rodent models. These encouraging results from animal models are not extrapolated to the same degree to human studies where, from the similar theoretical daily doses of anthocyanins in these studies, the opposite results were reported. Nevertheless, it is worth mentioning that the anthocyanin doses in the human studies carried out recently are low if we consider the estimated exposure to anthocyanins issued by the European Food Safety Agency (EFSA) or extremely low if we consider with caution the human equivalent dose based on body surface area from the preclinical dosage regimes used. Therefore, although some clinical data has demonstrated an inverse relation between anthocyanin consumption and BC/CRC, this could, in fact, be more relevant if we increase the daily human anthocyanin dose (as observed in animal model dose-effect studies) while new toxicological data for this flavonoid subtype are brought to light.

Phenol Biological Metabolites as Food Intake Biomarkers, a Pending Signature for a Complete Understanding of the Beneficial Effects of the Mediterranean Diet.

The Mediterranean diet (MD) has become a dietary pattern of reference due to its preventive effects against chronic diseases, especially relevant in cardiovascular diseases (CVD). Establishing an objective tool to determine the degree of adherence to the MD is a pending task and deserves consideration. The central axis that distinguishes the MD from other dietary patterns is the choice and modality of food consumption. Identification of intake biomarkers of commonly consumed foods is a key strategy for estimating the degree of adherence to the MD and understanding the protective mechanisms that lead to a positive impact on health. Throughout this review we propose potential candidates to be validated as MD adherence biomarkers, with particular focus on the metabolites derived from the phenolic compounds that are associated with the consumption of typical Mediterranean plant foods. Certain phenolic metabolites are good indicators of the intake of specific foods, but others denote the intake of a wide-range of foods. For this, it is important to emphasise the need to increase the number of dietary interventions with specific foods in order to validate the biomarkers of MD adherence. Moreover, the identification and quantification of food phenolic intake biomarkers encouraging scientific research focuses on the study of the biological mechanisms in which polyphenols are involved.

Variation in the Methylation of Caffeoylquinic Acids and Urinary Excretion of 3'-methoxycinnamic acid-4'-Sulfate After Apple Consumption by Volunteers.

INTRODUCTION: It has been reported that the phenolic metabolite 3'-methoxycinnamic acid-4'-sulfate generated from 5-O-caffeoylquinic acid may have potential benefits in human health. However, the variation in 3'- and 4'-methylation of 3',4'-dihydroxycinnamic acid and its impact on the yield of this sulfate metabolite is unclear and has been poorly studied. METHODS AND RESULTS: To address this aim, the excreted 3'-methoxy and 4'-methoxy metabolites in urine samples (24-h) are determined in 14 volunteers after an acute intake of 80 g of red-fleshed apple (RFA) or white-fleshed apple (WFA). These methoxy metabolites are also determined in the same volunteers in a second acute intake after a 6-week sustained consumption of the same products. CONCLUSION: Seven 3'-methoxy and seven 4'-methoxy metabolites are determined, i.e., the free cinnamic and corresponding phenylpropanoic acid, plus their sulfate, glucuronide, and glycine conjugates. In only six volunteers, five females and one male, is 4'-methylation preferred over 3'-methylation, but it is observed that an individual's 3'- : 4'-methylation ratio can change over time, and that the yield of 3'-methoxycinnamic acid-4'-sulfate is extremely variable, ranging from undetectable to 71% of the total C6 -C3 metabolites excreted, and any benefit accruing from this metabolite will not necessarily be available to all consumers.

Characterization of Tempranillo negro (VN21), a high phenolic content grapevine Tempranillo clone, through UHPLC-QqQ-MS/MS polyphenol profiling.

Grapevine cultivar and clone genotype is an important factor in the phenolic composition of wine. In this study, a new intense dark black berry color variant of Tempranillo, known as Tempranillo negro or VN21, is described. A targeted chromatographic approach based on UHPLC-QqQ-MS/MS was used to study the anthocyanins and non-colored phenols of the grape berry (skin and seeds) and wine. RJ43, one of the most cultivated clones in D.O.Ca. Rioja (Spain), was analyzed for comparison. Results suggest that the unique color of the grape skin in Tempranillo negro could be explained by higher concentrations of peonidin and cyanidin derivatives. This genotype accumulated anthocyanins in the seeds. Those differences in the berry were enhanced in the VN21 wines, which displayed notably higher concentrations of anthocyanins, and significantly increased contents of proanthocyanidins and stilbenes. This study exemplifies the application of phenol chromatographic analyses of spontaneous somatic variants to grapevine clonal selection.

Metabolic Fate and Cardiometabolic Effects of Phenolic Compounds from Red-Fleshed Apple in Hypercholesterolemic Rats: A Comparative Study with Common White-Fleshed Apple. The AppleCOR Study.

The present study aims to investigate the metabolic fate and the cardiometabolic effects of phenolic compounds provided by a red-fleshed apple variety biofortified in anthocyanins (ACN). Wistar rats are fed with high-fat diet (HFD) to induce hypercholesterolemia and supplemented with red-fleshed apple (HFD+R), white-fleshed apple (HFD+W), or an ACN-rich infusion from aronia fruit (HFD+A) providing matched content and profile of ACN. Plasma biochemical parameters, histological analysis, and phenol biological metabolites are determined. Plasma, urine, and feces show a significant increase of ACN metabolites after HFD+R and HFD+A, while flavan-3-ols are significantly increased after HFD+W and dihydrochalcones derivatives increased after both apples supplementation. A cardioprotective effect is observed after both apples and aronia infusion supplementation in the reduction of aortic thickness. The kidney function is improved after all supplementations and a decrease in insulin plasma concentration after both apples supplementation (HFD+R and HFD+W) is also observed. The findings support that ACN without apple matrix can induce cardioprotective effects. ACN or flavan-3-ols, together with dihydrochalcones, compose a phenolic phytocomplex in red- and white-fleshed apples, respectively, which can act synergistically in the attenuation of cardiovascular outcomes in hypercholesterolemic rats.

Virgin Olive Oil Phenolic Compounds Modulate the HDL Lipidome in Hypercholesterolaemic Subjects: A Lipidomic Analysis of the VOHF Study.

SCOPE: The lipidomic analysis of high-density lipoprotein (HDL) could be useful to identify new biomarkers of HDL function. METHODS AND RESULTS: A randomized, controlled, double-blind, crossover trial (33 hypercholesterolaemic subjects) is performed with a control virgin olive oil (VOO), VOO enriched with its own phenolic compounds (FVOO), or VOO enriched with additional phenolic compounds from thyme (FVOOT) for 3 weeks. HDL lipidomic analyses are performed using the Lipidyzer platform. VOO and FVOO intake increase monounsaturated-fatty acids (FAs) and decrease saturated and polyunsaturated FAs in triacylglyceride (TAG) species, among others species. In contrast, FVOOT intake does not induce these FAs changes. The decrease in TAG52:3(FA16:0) after VOO intake and the decrease in TAG52:5(FA18:2) after FVOO intake are inversely associated with changes in HDL resistance to oxidation. After FVOO intake, the decrease in TAG54:6(FA18:2) in HDL is inversely associated with changes in HDL cholesterol efflux capacity. CONCLUSION: VOO and FVOO consumption has an impact on the HDL lipidome, in particular TAG species. Although TAGs are minor components of HDL mass, the observed changes in TAG modulated HDL functionality towards a cardioprotective mode. The assessment of the HDL lipidome is a valuable approach to identify and characterize new biomarkers of HDL function.

Phosphoproteomic Analysis and Protein-Protein Interaction of Rat Aorta GJA1 and Rat Heart FKBP1A after Secoiridoid Consumption from Virgin Olive Oil: A Functional Proteomic Approach.

Protein functional interactions could explain the biological response of secoiridoids (SECs), main phenolic compounds in virgin olive oil (VOO). The aim was to assess protein-protein interactions (PPIs) of the aorta gap junction alpha-1 (GJA1) and the heart peptidyl-prolyl cis-trans isomerase (FKBP1A), plus the phosphorylated heart proteome, to describe new molecular pathways in the cardiovascular system in rats using nanoliquid chromatography coupled with mass spectrometry. PPIs modified by SECs and associated with GJA1 in aorta rat tissue were calpain, TUBA1A, and HSPB1. Those associated with FKBP1A in rat heart tissue included SUCLG1, HSPE1, and TNNI3. In the heart, SECs modulated the phosphoproteome through the main canonical pathways PI3K/mTOR signaling (AKT1S1 and GAB2) and gap junction signaling (GAB2 and GJA1). PPIs associated with GJA1 and with FKBP1A, the phosphorylation of GAB2, and the dephosphorylation of GJA1 and AKT1S1 in rat tissues are promising protein targets promoting cardiovascular protection to explain the health benefits of VOO.

Thermal and non-thermal processing of red-fleshed apple: how are (poly)phenol composition and bioavailability affected?

The present study evaluated the impact of different thermal (infrared-drying, hot air-drying and purée pasteurization) and non-thermal (freeze-drying) processing technologies on red-fleshed apple (poly)phenolic compounds. We further investigated the processing effect on the (poly)phenol bioavailability in a crossover postprandial study where three subjects consumed three apple products (freeze-dried snack, hot air-dried snack and pasteurized purée). (Poly)phenolic compounds present in the apple products and their biological metabolites in urine were analyzed using liquid chromatography coupled to mass spectrometry (UPLC-MS/MS). When comparing different processes, infrared-drying caused important losses in most of the apple (poly)phenolics, while hot air-drying and purée pasteurization maintained approximately 83% and 65% of total (poly)phenols compared with the freeze-dried snack, respectively. Anthocyanins in particular were degraded to a higher extent, and hot air-dried apple and pasteurized purée maintained respectively 26% and 9% compared with freeze-dried apple snack. The acute intake showed that pasteurized purée exhibited the highest (poly)phenol bioavailability, followed by hot air-drying and freeze-dried snack, highlighting the impact of processing on (poly)phenols absorption. In conclusion, for obtaining affordable new red-fleshed apple products with enhanced (poly)phenol bioavailability, purée pasteurization and hot air-drying represent viable techniques. However, to obtain a red-fleshed apple snack with high anthocyanin content, freeze-drying is the technique that best preserves them.

Relationship between Wine Consumption, Diet and Microbiome Modulation in Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder leading to the most common form of dementia in elderly people. Modifiable dietary and lifestyle factors could either accelerate or ameliorate the aging process and the risk of developing AD and other age-related morbidities. Emerging evidence also reports a potential link between oral and gut microbiota alterations and AD. Dietary polyphenols, in particular wine polyphenols, are a major diver of oral and gut microbiota composition and function. Consequently, wine polyphenols health effects, mediated as a function of the individual's oral and gut microbiome are considered one of the recent greatest challenges in the field of neurodegenerative diseases as a promising strategy to prevent or slow down AD progression. This review highlights current knowledge on the link of oral and intestinal microbiome and the interaction between wine polyphenols and microbiota in the context of AD. Furthermore, the extent to which mechanisms bacteria and polyphenols and its microbial metabolites exert their action on communication pathways between the brain and the microbiota, as well as the impact of the molecular mediators to these interactions on AD patients, are described.

Phenol-Enriched Virgin Olive Oil Promotes Macrophage-Specific Reverse Cholesterol Transport In Vivo.

The intake of olive oil (OO) enriched with phenolic compounds (PCs) promotes ex vivo HDL-mediated macrophage cholesterol efflux in humans. We aimed to determine the effects of PC-enriched virgin OO on reverse cholesterol transport (RevCT) from macrophages to feces in vivo. Female C57BL/6 mice were given intragastric doses of refined OO (ROO) and a functional unrefined virgin OO enriched with its own PC (FVOO) for 14 days. Our experiments included two independent groups of mice that received intragastric doses of the phenolic extract (PE) used to prepare the FVOO and the vehicle solution (saline), as control, for 14 days. FVOO intake led to a significant increase in serum HDL cholesterol and its ability to induce macrophage cholesterol efflux in vitro when compared with ROO group. This was concomitant with the enhanced macrophage-derived [3H]cholesterol transport to feces in vivo. PE intake per se also increased HDL cholesterol levels and significantly promoted in vivo macrophage-to-feces RevCT rate when compared with saline group. PE upregulated the expression of the main macrophage transporter involved in macrophage cholesterol efflux, the ATP binding cassettea1. Our data provide direct evidence of the crucial role of OO PCs in the induction of macrophage-specific RevCT in vivo.