Soil effect on proanthocyanidins composition of red and white wines obtained from Nero d'Avola and Grillo Vitis vinifera L. Cultivars.

In this study, the effects of the main soil chemical-physical parameters (i.e. texture, pH, total carbonates, cation exchange capacity, electric conductivity, organic matter and mineral endowment) on proanthocyanidin composition of Nero d'Avola red wines and Grillo white wines were investigated. Monomer proanthocyanidins (i.e. (+)-catechin and (-)-epicatechin) and oligomer proanthocyanidins (i.e. B1, B2, B3 and B4 dimers and C1 trimer), as well as proanthocyanidins subunit composition, percentage of galloylation, percentage of prodelphinidins and mean degree of polymerization, were studied for each wine. Results highlighted that the proanthocyanidins composition of both red and white wines is greatly affected by soil. In particular, the proanthocyanidins composition of Nero d'Avola red wines appeared to be affected by the soil physical-chemical parameters related to nutrients dynamics (CEC, EC, pH, organic matter, mineral endowment), whereas the proanthocyanidins composition of Grillo white wines was mainly influenced by the soil texture, that modulates soil water dynamics.

Color Characterization of Bordeaux Red Wines Produced without Added Sulfites.

Nowadays, the development of naturalness as a concept is illustrated in the oenological field by the development of wine produced with lower inputs, sometimes even without any addition of SO2 throughout the winemaking process, up to the bottling stage. Despite the increase in the offer of these wines, they remain poorly explored in the literature and require characterization. This study was developed to evaluate the color of Bordeaux red wines without SO2 addition using colorimetric and polymeric pigments analysis. From a batch of commercial Bordeaux red wines with and without SO2 addition, and experimental wines produced from homogenous grapes according to different winemaking processes, colorimetric analyses (CIELab and color intensity (CI)) revealed a large difference in wine color depending on the presence or absence of SO2. Indeed, wines without SO2 were significantly darker and presented with a deeper purplish color. According to these observations, polymeric pigments were quantified using UPLC-DAD/ESI QTof, and a higher concentration of polymeric pigments bound by the ethylidene bridge was observed in wines without SO2. This correlated with differences observed for CIELab and CI. Finally, a comparison with polymeric tannins bound by ethylidene bridge was made and revealed that no differences were observed between wines with and without added SO2. This underlines the affinity difference between tannins and anthocyanins to react with acetaldehyde to form ethylidene bridges.

CRISPR-Cas9-Based Technology and Its Relevance to Gene Editing in Parkinson's Disease.

Parkinson's disease (PD) and other chronic and debilitating neurodegenerative diseases (NDs) impose a substantial medical, emotional, and financial burden on individuals and society. The origin of PD is unknown due to a complex combination of hereditary and environmental risk factors. However, over the last several decades, a significant amount of available data from clinical and experimental studies has implicated neuroinflammation, oxidative stress, dysregulated protein degradation, and mitochondrial dysfunction as the primary causes of PD neurodegeneration. The new gene-editing techniques hold great promise for research and therapy of NDs, such as PD, for which there are currently no effective disease-modifying treatments. As a result, gene therapy may offer new treatment options, transforming our ability to treat this disease. We present a detailed overview of novel gene-editing delivery vehicles, which is essential for their successful implementation in both cutting-edge research and prospective therapeutics. Moreover, we review the most recent advancements in CRISPR-based applications and gene therapies for a better understanding of treating PD. We explore the benefits and drawbacks of using them for a range of gene-editing applications in the brain, emphasizing some fascinating possibilities.

Identification, quantitation and sensory contribution of new C-glucosidic ellagitannin-derived spirit compounds.

Ellagitannins are the main extractible phenolic compounds in oak wood. They can be extracted by eaux-de-vie aging in barrels but rapidly undergo chemical transformations, such as hydrolysis, reduction, oxidation, or even substitution reactions. Given gaps in knowledge about their composition in spirits, the goal of this work was to explore ellagitannin behavior during Cognac eaux-de-vie aging and search for new C-glucosidic ellagitannin-derived compounds. A purification protocol was followed to isolate the new formed compounds. UPLC-UV-Q-ToF and NMR spectroscopy were used to characterize a new C-glucosidic ellagitannin, named brandy tannin B. Two new forms of whiskey tannins were also isolated. The new compound, Brandy tannin B along with ß-1-O-ethylvescalagin and ß-1-O-ethylvescalin, and whiskey tannins were identified and quantified for the first time in Cognac eaux-de-vie. In addition, the organoleptic impact of brandy tannin B was evaluated. This work brings new insights into ellagitannin composition and their contribution to spirit quality.

Impact of Barrel Toasting on Ellagitannin Composition of Aged Cognac Eaux-de-Vie.

It is well established that C-glucosidic ellagitannins contribute to wine quality, and new forms of ellagitannins have been found recently in cognac eaux-de-vie. The contribution of some ellagitannin-derived spirit compounds to eaux-de-vie taste has been demonstrated recently. However, there is a gap in our knowledge of the content, composition, and evolution of C-glucosidic ellagitannins in this matrix. Indeed, the quantification of these compounds and their evolutionary compounds have never before been researched in cognac eaux-de-vie. Thus, the aim of this study was not only to quantify these compounds, but also to study their kinetics and to observe how they are impacted by barrel toasting. For this purpose, barrels representing eight different toasting levels were used to age the same eau-de-vie during the first 18 months. Ellagitannin quantification was carried out by HPLC-Triple quadrupole. The results showed that the evolutionary trend of the eight ellagitannins is the same for all eight types of barrel toasting. The maximum concentrations of C-glucosidic ellagitannins were found after 3 months of aging (up to 23 mg/L) before decreasing to 18 months (9.7 mg/L), whereas ellagitannin-derived spirit compound concentrations increased throughout aging (up to 130.9 mg/L). In addition, barrel toasting had such an impact on ellagitannin content that barrels could be differentiated according to their levels. Eaux-de-vie in barrels with high toasting were lower in ellagitannins concentrations.

Oxyresveratrol and Gnetol Glucuronide Metabolites: Chemical Production, Structural Identification, Metabolism by Human and Rat Liver Fractions, and In Vitro Anti-inflammatory Properties.

Stilbene metabolites are attracting great interest because many of them exhibit similar or even stronger biological effects than their parent compounds. Furthermore, the metabolized forms are predominant in biological fluids; therefore, their study is highly relevant. After hemisynthesis production, isolation, and structural elucidation, three glucuronide metabolites for oxyresveratrol (ORV) were formed: trans-ORV-4'-O-glucuronide, trans-ORV-3-O-glucuronide, and trans-ORV-2'-O-glucuronide. In addition, two glucuronide metabolites were obtained for gnetol (GN): trans-GN-2'-O-glucuronide and trans-GN-3-O-glucuronide. When the metabolism of ORV and GN is studied in vitro by human and rat hepatic enzymes, four of the five hemisynthesized compounds were identified and quantified. Human enzymes glucuronidated preferably at the C-2' position, whereas rat enzymes do so at the C-3 position. In view of these kinetic findings, rat enzymes have a stronger metabolic capacity than human enzymes. Finally, ORV, GN, and their glucuronide metabolites (mainly at the C-3 position) decreased nitric oxide, reactive oxygen species, interleukin 1ß, and tumor necrosis factor α production in lipopolysaccharide-stimulated macrophages.

Evolution of the Crown Procyanidins' Tetramer during Winemaking and Aging of Red Wine.

Condensed tannins play a major role in the quality of red wine. After grape extraction, they quickly evolve thanks to different oxidation mechanisms. Recently, NMR identified a new sub class of condensed tannins, named crown procyanidins, in red wine. The crown procyanidins' tetramer exhibits a macrocyclic structure composed of four (-)-epicatechin with an unusual cavity in the center of the molecule. These new tannins exposed a higher polarity than the linear tannins. In this work, the evolution kinetics of these crown procyanidins during the winemaking process and after aging of red wine in bottles were studied. Samples' quantification was analyzed by UPLC-UV-Q-TOF. The concentration of cyclic and non-cyclic procyanidins was compared. During the winemaking process, crown procyanidins are mainly extracted at the beginning of the alcoholic fermentation and they remain stable until the end of the winemaking process. The high polarity and solubility of this new molecule in water was confirmed. During the aging of red wine in bottles, crown procyanidins' concentrations are stable, whereas the non-cyclic tannins decrease dramatically. Finally, a strong oxygenation experiment confirmed the crown procyanidins' resistance to oxidation and unique skills.

Trans-ε-Viniferin Encapsulation in Multi-Lamellar Liposomes: Consequences on Pharmacokinetic Parameters, Biodistribution and Glucuronide Formation in Rats.

Trans-ε-viniferin (εVin) is a resveratrol dimer exhibiting promising biological activities for human health. Its bioavailability being low, the development of encapsulation methods would be used to overcome this issue. The aim of this study was to measure the consequences of the encapsulation of εVin in multilamellar liposomes on its pharmacokinetic parameters, metabolism and tissue distribution in rats. After oral administration of εVin (20 mg/kg body weight), either as free or encapsulated forms, plasmas were sequentially collected (from 0 to 4 h) as well as liver, kidneys and adipose tissues (4 h after administration) and analyzed by LC-HRMS. The glucuronide metabolites (εVG) were also produced by hemisynthesis for their quantification in plasma and tissues. The encapsulation process did not significantly modify the pharmacokinetic parameters of εVin itself. However, a significant increase of the T1/2 was noticed for εVG after administration of the encapsulated form as compared to the free form. An accumulation of εVin and εVG in adipose tissues was noticed, and interestingly a significant increase of the latter in the mesenteric one after administration of the encapsulated form was highlighted. Since adipose tissues could represent storage depots, and encapsulation allows for prolonging the exposure time of glucuronide metabolites in the organism, this could be of interest to promote their potential biological activities.

Pomegranate Juice Ameliorates Dopamine Release and Behavioral Deficits in a Rat Model of Parkinson's Disease.

Pomegranate juice (PJ) is a rich source of ellagitannins (ETs), precursors of colonic metabolite urolithin A, which are believed to contribute to pomegranate's neuroprotective effect. While many experimental studies involving PJ's role in Alzheimer's disease and hypoxic-ischemic brain injury have been conducted, our knowledge of pomegranate's effects against Parkinson's disease (PD) is very limited. Previously, we have reported that PJ treatment improved postural stability, which correlated well with enhancement of neuronal survival, protection against oxidative damage, and α-synuclein aggregation. Since olfactory and motor deficits are typical symptoms of PD, in this study, we aimed to investigate the capability of PJ to protect against olfactory, motoric, and neurochemical alterations. To evaluate its efficiency, Wistar rats were given a combined treatment with ROT (1.3 mg/kg b.w./day, s.c.) and PJ (500 mg/kg/day, p.o.) for 35 days. After this, we assessed the olfactory discrimination index (DI) and vertical and horizontal activities as well as levels of dopamine and its main metabolite 3,4-Dihydroxyphenylacetic acid (DOPAC) in the dissected midbrain of animals. Our findings provide the first evidence that PJ treatment protects against ROT-induced DA depletion in the midbrain, which correlates well with improved olfactory function and vertical activity as well as with the presence of urolithin A in the brain.

Use of alimentary film for selective sorption of haloanisoles from contaminated red wine.

Haloanisoles (HAs) are known to compromise wine quality because of their mouldy off-flavours. Up to now no treatment exists to eliminate the presence of these unpleasant volatiles in wine. This research aimed i) to assess the alimentary plastic film efficacy to remove or lessen HAs content in polluted wines; and ii) to evaluate its impact on wine quality. The film-treatment reduced significantly (p < 0,05) the 2,4,6-trichloroanisole (TCA) content of initial wine. This decrease became more noticeable as the contact time film-wine increased. Chromatic characteristics, phenolic and proanthocyanidin contents, and woody aroma profile did not change because of the film-treatment. A significant sorption of certain esters was observed, but as HAs were removed under detection thresholds, fruity perception of wines was improved. Globally, the alimentary plastic film was able to improve the organoleptic quality of wines contaminated with HAs, by reducing the cork taint and enhancing their overall fruity aroma.

Grapes and their derivatives in modulation of cognitive decline: a critical review of epidemiological and randomized-controlled trials in humans.

With an increase in life expectancy, the incidence of chronic degenerative pathologies such as dementia has progressively risen. Cognitive impairment leads to the gradual loss of skills, which results in substantial personal and financial cost at the individual and societal levels. Grapes and wines are rich in healthy compounds, which may help to maintain homeostasis and reduce the risk of several chronic illnesses, including dementia. This review analyzed papers that were systematically searched in PubMed, MEDLINE, Embase, and CAB-Abstract, using the association between grapes (or their derivatives) and their effects on cognitive functions in humans. Analysis was restricted to epidemiological and randomized-controlled studies. Consumption of grape juice (200-500 mL/day) and/or light-to-moderate wine (one to four glasses/day) was generally associated with improved cognitive performance, while the results for other alcoholic beverages were controversial and inconclusive. Bioactive molecules contained in grapes and wine were also considered, with particular attention paid to resveratrol. Due to the relatively high doses required (150-1000 mg/day) for bioactivity coupled with its low bioavailability, resveratrol is only one of the possible grape-derived compounds that may partly underpin the beneficial effects of grapes on the central nervous system.

Validation of a mass spectrometry method to identify and quantify ellagitannins in oak wood and cognac during aging in oak barrels.

Ellagitannins are the main extractible phenolic compounds in oak wood; the monomers vescalagin and castalagin, lyxose/xylose-bearing monomers grandinin and roburin E, dimers roburins A and D and lyxose/xylose-bearing dimers roburins B and C are the principal ones. These compounds are responsible for the high durability of wood and may contribute to the organoleptic quality of wines and spirits (color, astringency, bitterness). Despite their importance, their presence and forms in distilled spirits are not well known. The aim of this work was therefore to develop and validate a method to identify and quantify oak wood ellagitannins in Cognac using high liquid chromatography-triple quadrupole (LC-QQQ) analysis. The method was validated using vescalagin as the standard and by studying sensitivity, linearity in working range, intraday repeatability, and intraday precision in order to quantify individual ellagitannins in this complex matrix.

Effect of enological treatments on phenolic and sensory characteristics of red wine during aging: Micro-oxygenation, sulfur dioxide, iron with copper and gelatin fining.

This work aimed to study long-term impact of micro-oxygenation and/or different aging treatments: (i) high SO2, (ii) high Fe with Cu and (iii) gelatin fining on Plavac mali red wine phenolic and in-mouthfeel sensory development in barrels and furthermore in bottles. Results showed that outcomes of micro-oxygenation strongly depend on aging treatments. High SO2 concentration during aging in barrels and bottles delayed typical phenolic changes and slightly contributed to astringency and lower color intensity, particularly in wine that was not micro-oxygenated. High metal concentrations and gelatin fining promoted intensive polymerization of proanthocyanins and a lower percentage of prodelphinidins after long-term aging in barrels. Also, flavan-3-ol and anthocyanins transformation rates in micro-oxygenated wines of both treatments significantly differed from their controls. Gelatin fining proved to be a very effective treatment for astringency reduction, particularly when combined with micro-oxygenation, but fined wines after long term aging in bottles showed lower color intensity.

Is it scientifically justifiable to exclude wine and/or unfermented grape derivatives from the diet of consumers with or at risk of developing type-2 diabetes?

The abuse of alcoholic beverages has been associated with an increased risk of chronic-degenerative diseases, including diabetes mellitus, so that there is a general diffidence towards the low/moderate consumption of wine by individuals with type-2 diabetes (T2D) or at risk of developing it. This narrative review investigates by critical revision of the scientific literature whether wine/grape derivatives must be excluded or if their low/moderate consumption could be part of the daily diet of T2D individuals. Although further intervention studies on the consumption of alcoholic beverages and the development or control of T2D are needed, the burden of evidence suggests that low/moderate wine consumption could have beneficial effects.

New C-Glycosidic Ellagitannins Formed upon Oak Wood Toasting; Identification and Sensory Evaluation.

In the courses of studies on ellagitannin changes during oak wood toasting, two C-glycosidic ellagitannins were isolated from the french oak wood for the first time. These two compounds exhibited [M-H]- ion peak at m/z 1055.0631 (compound A) and at m/z 1011.0756 (compound B). A compound is named Castacrenin E and is produced by Castacrenin D oxidation. Castacrenin D is a vescalagin with an additional aromating ring to the C-1 through a C-C bond. These compounds are not only found under laboratory conditions but also in commercial oak wood representing different toasting methods and sizes. Their levels are conditioned by oak wood dimensions and toasting degree. The wood pieces with the smallest size present almost two times more compounds A and B. Moreover, the compound B is the only compound to be present in medium toasting temperatures of the smallest wood pieces. Both of them can influence either astringency sensation or bitterness taste.

Impact of Different Stoppers on the Composition of Red and Rosé Lagrein, Schiava (Vernatsch) and Merlot Wines Stored in Bottle.

Different technical cork stoppers (blend of natural cork microgranules, one-piece natural cork, agglomerated natural cork, technical cork 1+1) were compared to evaluate the effects on the phenolic, volatile profiles and dissolved oxygen in three red (Merlot, Lagrein red, St. Magdalener) and one rosé (Lagrein rosé) wines, which were stored in bottles for 12 months. Gallic acid, caffeic acid, p-coumaric acid, trans-resveratrol, glutahionyl caftaric acid and protocatechuic acid did not vary remarkably during the first three months, whereas at six months a net increase was reported, followed by a clear decrease at 12 months. The same trend was observed in Lagrein rosé, but only for gallic acid. The total anthocyanins content decreased during the storage period in the four wines. Isopentyl acetate, 1-hexanol, ethyl hexanoate, 2-phenylethyl alcohol, diethyl succinate, ethyl octanoate and ethyl decanoate were the main volatile compounds. The sum of alcohols decreased in all four of the wines. The esters decreased in Merlot; however, they increased in Lagrein rosé, Lagrein red and St. Magdalener during the storage. Univariate and multivariate statistics and a sensory discriminant triangle test displayed similar influences of the different stoppers on the phenolic and volatile compounds during the whole storage duration. The changes detected in the phenolic and volatile concentrations were presumably due to the non-oxygen-mediated reactions occurring during 12 months of storage in bottle.

Oenological tannins to prevent Botrytis cinerea damage in grapes and musts: Kinetics and electrophoresis characterization of laccase.

Enzymatic parameters (KM and Vmax), residual activity, effect of bentonite and electrophoresis characterization of laccase in the presence of different oenological tannins (OT) were investigated in relation to B. cinerea negative effects in grapes and musts. Five OT were tested (gallotannin, ellagitannin, quebracho, grape-skin and grape-seed) in comparison with ascorbic acid (AA), sulfur dioxide (SO2) and bentonite. We added OT, AA, SO2 and bentonite to botrytized must obtained by inoculation of grapes with B. cinerea strain 213. Laccase activity was measured by the syringaldazine method at different concentrations of substrate. Enzymatic parameters were determined using Michaelis-Menten and Lineweaver-Burk plots. The B. cinerea strain was also grown in a liquid medium for laccase production. Molecular weight of laccases and effect of OT upon these laccases were studied by SDS-PAGE. Results confirm that bentonite, contrary to OT, did not permit to reduce laccase activity. Regardless the tannin considered, Vmax, KM and laccase activity were reduced and gallotannin, grape-skin and grape-seed tannin presented the greatest ability. Efficiency of grape-seed tannin addition in order to reduce the laccase activity, was comparable to that of AA or SO2 at the typical doses employed in oenology for each one. Oenological tannins appear to be excellent processing aids to prevent laccase effects and contribute to reduce the use of SO2 in grapes and musts.

High-Performance Liquid Chromatography-Hydrogen/Deuterium Exchange-High-Resolution Mass Spectrometry Partial Identification of a Series of Tetra- and Pentameric Cyclic Procyanidins and Prodelphinidins in Wine Extracts.

A solid-phase extraction method was applied for the identification of a series of unconventional crown (macrocyclic) B-type proanthocyanidin tetramers (m/z 1169.2557, 1185.2507, 1201.2456, and 1217.2405) and pentamers (m/z 1457.3191, 1473.3140, 1489.3090, 1505.3039, and 1521.2988) containing (epi)catechins only (procyanidins) or (epi)catechins and (epi)gallocatechins (prodelphinidins). These compounds were identified in red wine by high-performance liquid chromatography-high-resolution mass spectrometry coupled with online hydrogen/deuterium exchange (HDX) after purification with a C18 solid-phase extraction phase from the original wine sample. The number and type of monomer units present in each procyanidin and prodelphinidin are discussed on the basis of the experimental measured masses, their retention time distribution among observed isomers, tandem mass spectrometry fragmentations, and the HDX-induced shift of the theoretical monoisotopic mass. The elution in reverse-phase high-performance liquid chromatography shifted to lower retention times when the ratio of (epi)gallocatechin units in these molecules increased with respect to the content of (epi)catechin units, as a consequence of the increase of polarity.

Effect of extraction time on content, composition and sensory perception of proanthocyanidins in wine-like medium and during industrial fermentation of Cabernet Sauvignon.

BACKGROUND: The research objectives focused on the extraction of grape tannins during extended maceration. Skins and seeds were extracted separately in a wine-like medium. In parallel, the same grapes were fermented in industrial tanks. The content and structural characteristics of extractable proanthocyanidins (PAs) were determined spectrophotometrically and using UHPLC-DAD-MS/MS, respectively. Skin, seed extracts and fermented wines were characterized in chemical and sensorial terms after different extraction durations. RESULTS: The extraction of high molecular-weight PAs (HMWPs) from seeds increased for up to 20 days, whereas low molecular-weight PAs (LMWPs) reached a plateau earlier. The extraction of HMWPs and LMWPs from skins reached a maximum at the first sampling. Sensory evaluation confirmed greater astringency and bitterness of seed extracts with increasing time. Neither seed nor skin extracts differed statistically in terms of the mean degree of polymerization (mDP) and percentage of galloylation (%G) on different extraction days (except for seeds at the first sampling). During industrial maceration, HMWPs and LMWPs increased up to 12.7% alcohol (9 days of maceration); thereafter, the increase was not significant, whereas the mDP, %G and percentage of prodelphinidins did not significantly change after 11.4% alcohol. There were positive correlations with the wine astringency and PA content. CONCLUSION: Looking at both simulated and industrial maceration, it can be concluded that, with a longer maceration time, the increase in HMWP content was more evident than PA structural changes. The increasing content of tannins from seeds played an important role in the greater astringency and bitterness of Cabernet Sauvignon macerated at length. © 2019 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Disease Resistant Bouquet Vine Varieties: Assessment of the Phenolic, Aromatic, and Sensory Potential of Their Wines.

The search for grape varieties resistant to diseases and to climatic changes notably concerns the wine industry. Nine monovarietal wines from new red grape varieties resistant to cryptogamic diseases (downy and powdery mildews) were evaluated in terms of their total phenolic, anthocyanin and proanthocyanidin contents, anthocyanin profile, volatile composition, and sensory attributes. Thus, the question remains, will these hybrid grapes (≥97.5% of Vitisvinifera genome) lead to wines with organoleptic properties similar to those of Vitisvinifera wines that consumers are used to? Total phenolic (1547-3418 mg GA/L), anthocyanin (186-561 mg malvidin/L), and proanthocyanidin (1.4-4.5 g tannins/L) contents were in broad agreement with those previously described in the literature for monovarietal wines produced with well-known red grape varieties (Cabernet Sauvignon, Merlot, Syrah). With regard to fruity aroma, ethyl esters of straight-chain fatty acids (530-929 µg/L) stood out clearly as the major volatile components for all hybrid wines considered. Sensory analysis revealed significant differences (p < 0.05) for visual aspect, aroma, flavor, global balance, astringency, and body. Overall, these new hybrid grape varieties are not only resistant to cryptogamic diseases, but also present enough potential to become quality wines, since their phenolic and volatile attributes are close to those of common red monovarietal wines.