Les flavan-3-ols appartiennent à la famille des polyphénols retrouvés dans diverses plantes et majoritairement dans le raisin. Ils jouent un rôle primordial dans les mécanismes de défense des plantes, influent sur les propriétés organoleptiques du vin et sont potentiellement bénéfiques au niveau de la santé humaine. La voie de biosynthèse des flavanols monomères est décrite dans la littérature. Cependant, les mécanismes de formation des proanthocyanidines (polymères) sont inconnus à ce jour. Des études ont montré que les flavanols glycosylés sont des intermédiaires potentiels dans la biosynthèse des PA et permettent le transport des unités de flavanols du cytoplasme vers la vacuole de la cellule, où a lieu la polymérisation. Un criblage global des flavanols glycosylés présents dans des raisins à trois stades de développement et dans des vins de différents cépages a été réalisé en analysant séparément les pellicules et les pépins de raisin par une méthode d’UPLC-DAD-ESI-MS. La teneur de ces composés dépend de paramètres de type variété du raisin, tissu biologique étudié et stade de maturité. La présence de dimères de flavanol glycosylés a été montrée pour la première fois dans le raisin. Grâce à l’hémisynthèse de la (+)-catéchine 4’-O--glucoside et 7-O--glucoside, certains monomères ont été caractérisés comme appartenant à la classe des -glucosides. Une étude quantitative a montré l’évolution des flavanols glycosylés au cours du développement de la baie de raisin (pépins et pellicules séparés) provenant de trois cépages différents. Les monomères et dimères d’ (épi) catéchine diglycosylés ont été découverts pour la première fois et uniquement dans les pépins. Une diminution en monomères d’ (épi) catéchine monoglycosylés a été observée dans la pellicule au cours de la maturation du raisin. Les dimères d’ (épi) catéchine monoglycosylés s’accumulent un peu après le stade de véraison et diminuent ensuite à maturité. Les monomères et dimères d’ (épi) catéchine diglycosylés s’accumulent dans les pépins au cours de la maturation. Finalement, l’évolution des teneurs en flavanols mono et diglycosylés au cours de microvinifications a été étudiée. On observe des profils d’extraction similaires pour les deux variétés utilisées (Grenache et Syrah). La quantité totale des différentes familles de composés augmente au cours de la vinification, et ensuite diminue en fin de FA. Certains composés sont dégradés préférentiellement, suggérant la présence d’activités glycosidases spécifiques du raisin ou de la levure. / Flavan-3-ols belong to a group of polyphenols present in a wide variety of plants, and particularly in grapeberries. They play an important role in defense mechanisms in plants, have a significant impact on wine organoleptic properties; and their beneficial effects on human health may help to protect against chronic diseases such as atherosclerosis. The sequence of common flavanol monomer biosynthesis is widely described in the literature, but the formation mechanisms of proanthocyanidins (PA) remain unknown. Studies show that flavanol glycosides are potential intermediates in PA polymerization and have transporter roles of monomeric units from cytoplasm to vacuole in cell, where polymerization takes place. Global screening of grapeberry flavanol glycosides were carried out at three stages of grape development and in wines of different varieties; skin and seeds were measured separately using an UPLC-DAD-ESI-MS method. The composition of the target isomers depends on different parameters such as tissue type or stage of development. The presence epi catechin monoglycoside is reported here for the first time in grapes. Using (+)-catechin 4’-O--glucoside and 7-O--glucoside hemisynthesis, several monomers were shown to -glucosides. Quantitative analysis demonstrates the evolution of flavanol glycosides in both skin and seeds during the development of three grapevine varieties. For the first time monomeric and dimeric (epi) catechin diglycosides were revealed and shown accumulate only in grape seeds during ripening. A reduction in the concentration of monomeric (epi) catechin monoglycoside was observed during grape skin development. Dimeric (epi) catechin monoglycosides accumulate after veraison and then decrease at the end of grape ripening. The extraction profiles of flavanol glycosides during red grape fermentation showed similar evolution patterns for both varieties used. The total concentration of different compound families increases during winemaking, and then decreases at the end of fermentation. Degradation of specific compounds was observed at the end of fermentation which may be explained by the activity of glycosidases from grape extracts released during fermentation and pressing.

The prevalence of obesity and diabetes is increasing in the United States and abroad and strategies are needed to prevent the progression from an at-risk state to the clinically diagnosed diseases. Flavanols in cocoa powder have been shown to reduce blood glucose concentrations, improve insulin sensitivity, and decrease gut permeability in animals and humans, but it is unknown if this occurs in adults with prediabetes. Therefore, we first hypothesized that an acute dose of cocoa would reduce postprandial glucose and enhance insulin and incretin hormone responses to a mixed meal challenge compared to a placebo. Second, we hypothesized that 15 g cocoa/day for 4-weeks would reduce gut permeability, attenuate endotoxin response to a high fat meal, improve insulin sensitivity, and improve measures of skeletal muscle substrate flexibility in a randomized, double blinded, placebo controlled parallel group design. To test the first hypothesis, 30 overweight or obese volunteers who were at-risk for diabetes completed two meal challenges using a randomized crossover design. Blood samples were collected hourly for 4 hours and were analyzed for glucose, insulin, C-peptide, glucagon-like peptide 1 (GLP-1), and gastric inhibitory peptide (GIP). Cocoa did not influence these measures. However, participants with the lowest fasting blood glucose concentrations were more likely to respond to the cocoa as hypothesized. To test our second hypothesis, 15 overweight or obese adults at risk for developing diabetes consumed either the cocoa or placebo treatments along with a controlled diet for one month. Overall, cocoa did not seem to influence insulin sensitivity, gut permeability, or endotoxin levels, although cocoa may influence skeletal muscle substrate metabolism. In conclusion, the data for both studies suggests that cocoa did not exert substantial effects on the evaluated outcomes. However, the experiments did provide valuable information about incretin hormone levels in adults with impaired glucose tolerance. More research is needed to understand how cocoa can affect glucose homeostasis for overweight or obese adults. / Ph. D.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Dominika Sobolová Supervisor: Assoc. Prof. Přemysl Mladěnka, Pharm.D., Ph.D. Title of diploma thesis: Pharmacokinetics of flavanols This work is focusing on summarizing available information about the fate of flavanols in the organism. It is necessary to know the pharmacokinetics to explain their biological effects. In contrast to other flavonoids, they occur in the form of aglycones in plant foods. Galoylation, polymerization and optical isomerism have an important influence on the pharmacokinetics. Partial absorption of monomers begins in the small intestine after oral ingestion. In addition to the liver, the extensive metabolic changes take place even in the enterocytes. The resulting metabolites enter the circulation or they are effluxed back into the intestinal lumen, especially in the case of (epi)catechin sulfates. Epicatechin and catechin are present almost exclusively as glucuronides, sulfates or methylated compounds in the plasma. On the contrary, free unconjugated forms prevail within the gallates. The extent of their absorption is lower. They are excreted via biliary excretion, while other catechins are quickly eliminated by the kidneys in urine. The bioavailability of the parent...

Fisetin, a flavanol with anti-inflammatory, anti-cancer, and anti-aging properties, has shown promise for reducing fat accumulation in tissue culture and animal models. This plant sourced compound has limited studies supporting its effects on fat accumulation. Therefore, this study was completed to determine fisetin’s role in fat reduction along with its mechanism of action using Caenorhabditis elegans. C. elegans is a small roundworm with roughly 65% of its genes being conserved in humans related to disease. In this study, 100 and 200 µM fisetin has shown to reduce fat accumulation in wild-type worms. Body size, locomotion, and pumping rate were assessed in wild-type worms to determine if fisetin modified worm size, speed, and feed behavior, respectively. Mutant strains were tested to elucidate a potential pathway, of which tub-1 knockout mutants failed to reduce fat accumulation after fisetin treatment, suggesting this gene’s involvement. Gene expression of tub-1 was not altered by fisetin treatment, suggesting potential post-transcriptional regulation of fisetin. This study serves as an introduction to fisetin’s fat reducing effects via a tub-1 dependent mechanism.

<p>Kardiovaskulära sjukdomar och hypertoni blir allt mer vanligt i västvärlden. Trots livsstilsrekommendationer ökar antalet insjuknanden i hjärt-kärlsjukdomar, vilket har blivit en av de vanligaste dödsorsakerna i Sverige. Syftet med litteraturstudien var att undersöka om flavanol i kosten kan användas blodtryckssänkande samt att klargöra om flavanol påverkar den kardiovaskulära ohälsan. Metoden som användes var en litteraturstudie av redan publicerade vetenskapliga artiklar inom ämnet. Flertalet studier visar på att flavanol har en blodtryckssänkande likväl som andra positiva effekter. Många studiers resultat visar att flavanol har större effekt på de grupper som redan har kardiovaskulär ohälsa samt högt blodtryck. Forskningen är ny och har än inte hunnit utvärderas ordentligt, men den positiva påverkan hos flavanol är tydlig och det är inte svårt att se användbara områden för flavanol som terapeutisk metod, men även i hälsopromoterande syfte. Detta är något som skulle rimma väl med sjuksköterskans professionella ansvar att främja hälsa och motverka sjukdom. Trots de i dagsläget erhållna resultaten krävs mer och framför allt forskning med hög kvalitet.</p>

Kardiovaskulära sjukdomar och hypertoni blir allt mer vanligt i västvärlden. Trots livsstilsrekommendationer ökar antalet insjuknanden i hjärt-kärlsjukdomar, vilket har blivit en av de vanligaste dödsorsakerna i Sverige. Syftet med litteraturstudien var att undersöka om flavanol i kosten kan användas blodtryckssänkande samt att klargöra om flavanol påverkar den kardiovaskulära ohälsan. Metoden som användes var en litteraturstudie av redan publicerade vetenskapliga artiklar inom ämnet. Flertalet studier visar på att flavanol har en blodtryckssänkande likväl som andra positiva effekter. Många studiers resultat visar att flavanol har större effekt på de grupper som redan har kardiovaskulär ohälsa samt högt blodtryck. Forskningen är ny och har än inte hunnit utvärderas ordentligt, men den positiva påverkan hos flavanol är tydlig och det är inte svårt att se användbara områden för flavanol som terapeutisk metod, men även i hälsopromoterande syfte. Detta är något som skulle rimma väl med sjuksköterskans professionella ansvar att främja hälsa och motverka sjukdom. Trots de i dagsläget erhållna resultaten krävs mer och framför allt forskning med hög kvalitet.

The consequences of pre-fermentation and post-fermentation extended maceration (EM) on colour, mouthfeel and phenolic composition were investigated in Pinot noir (2004), Grenache (2006) and Shiraz (2007) (Vitis vinifera L.) wines. Experimental wines were made using cold soak, post-fermentation EM, and standard fermentation treatments (C). Cold soak treatments included a 3-day cold soak at 10°C (CS), with an additional comparison of plunging effects for the 2004 wines (CSP). Post-fermentation extended maceration treatments were 1- or 3-weeks on skins in 2004 (PS1 and PS3 respectively), and 3-weeks in 2006 and 2007 (PS3). A variety of chemical and sensory test methods were used to determine changes in phenolic components and organoleptic properties between treatments of all 3 varietals as they aged in the bottle. Among other results, it was determined if wines made with a period of cold soak had increased colour intensity, and increased concentrations of monomeric anthocyanins and pigmented polymers compared to control wines. It was also determined if wines made with a period of post-fermentation EM had increased concentrations of the flavan-3-ols (+)-catechin and (−)-epicatechin, and tannin, decreased colour intensity and modified mouthfeel compared to the other wine treatments. A greater understanding of Australian red winemakers’ opinions on EM regimes and their use in Australian wineries was obtained by survey. Survey results confirmed that EM is used extensively in Australian wineries but that winemakers have poor understanding of the consequences of EM regimes for red wine properties. The survey confirmed that winemakers are concerned about the economic cost and logistic pressures associated with the use of EM regimes during vintage. Wines made using EM need to spend longer in fermentation vessels, which are in high demand during this time. Findings from this study provide winemakers with more information to consider before making decisions about their use of EM regimes. Survey findings showed more winemakers would use EM regimes if logistic and economic pressures did not apply. However, results suggest that even if winemakers did adopt EM practices, some may not achieve what they believe to be the outcome of these regimes, such as improved colour or mouthfeel properties. For instance, results showed that cold soaking did not make a difference to wine colour compared to conventional fermentation maceration. Even without cold soaking red must, winemakers may be able to achieve the same or very similar wine organoleptic characteristics at a reduced cost. Similarly, no significant effects of plunging during cold soak were observed. Post-fermentation EM visibly reduced wine colour intensity and imparted a browner hue to the wine compared to red wine that was pressed off skins upon reaching dryness. This EM regime is therefore unlikely to benefit winemakers who are seeking to produce highly coloured wines. However, prolonged maceration post-fermentation did increase the intensity of perceived bitterness and increased the concentration of wine flavan-3-ols and tannins. Winemakers may therefore influence the desired balance between the extraction of these wine phenolics (and the associated outcome for taste and mouthfeel properties) and economic considerations by varying the duration of maceration post-fermentation. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1362928 / Thesis (Ph.D.) - University of Adelaide, School of Agriculture, Food and Wine, 2009.

En lien avec leur potentiel antioxydant, les composés phénoliques sont généralement associés à l'effet protecteur sur la santé d'une alimentation riche en fruits et légumes. Ils sont également fortement associés à la qualité organoleptique des cidres puisqu'ils affectent directement leur astringence, leur amertume, leur couleur et leurs arômes. Deux études ont récemment été publiées sur la détection de QTL des composés phénoliques des pommes de table. Aucune étude n'a encore été publiée pour les pommes à cidre, réputées pour leur forte teneur en composés phénoliques. L'objectif de cette thèse est d'identifier les régions génétiques impliquées dans la teneur en composés phénoliques d'une descendance de pommiers à cidre. Dans un premier temps, deux méthodes de quantification ont été développées et comparées en UHPLC-UV et UHPLC-MS/MS pour les principaux composés phénoliques du jus de pomme. Bien qu'il y ait des surestimations avec l'un des détecteurs pour certains composés, ces deux méthodes corrèlent très fortement. Des dosages ont également été réalisés sur fruit entier à l'INRA de Rennes. Une grande variabilité a été observée pour les fruits et les jus de cette descendance, représentative des principales variétés de pommes à cidre cultivées en Europe. 48 QTL ont été détectés sur neuf groupes de liaison (LG). Neuf clusters semblent particulièrement stables, indépendamment de l'année ou du matériel (fruit ou jus) étudié. Les enzymes de la biosynthèse des composés phénoliques et facteurs de transcription ont été ciblés pour l'identification des gènes candidats, réalisée au niveau des principaux QTL. Ces travaux proposent de nouvelles cibles pour la sélection assistée par marqueurs comme le QTL pour l'acide chlorogénique du LG17 pour l'amélioration des variétés de pommes à cidre