Introdução: O murici (Byrsonima crassifolia (L.) Kunth) é um fruto utilizado pela população como alimento ou como agente terapêutico, mas ainda há poucos estudos sobre as suas propriedades funcionais. Assim, este trabalho objetivou caracterizar os frutos do murici quanto à composição de compostos antioxidantes e avaliar seus mecanismos de ação antioxidante in vitro. Metodologia: Os frutos do murici foram coletados na cidade de Araiozes, Maranhão, Brasil. A composição centesimal foi avaliada pelos métodos oficiais de análise e o perfil de minerais por espectrometria de emissão ótica com plasma indutivamente acoplado. Os perfis de carotenóides, tocoferóis e vitamina C foram determinados por comatografia líquida de alta eficiência. As condições ótimas para a extração de polifenóis de murici foram definidas por meio de planejamento composto central rotacional. Assim, o extrato A foi obtido usando 43,4 por cento de acetona a 28,9°C por 50,8 minutos e o extrato B com 45,2 por cento de acetona a 40°C por 52,8 minutos. Os extratos foram avaliados quanto ao perfil de compostos fenólicos por HPLC-ESI/MS e quanto aos mecanismos de ação antioxidante in vitro. Resultados: Os frutos de murici apresentaram (valor médio) 74,35 por cento de umidade, 0,94 por cento de cinzas, 0,68 por cento de proteínas, 1,82 por cento de lipídios, 4,31 por cento de carboidratos disponíveis e 17,91 por cento de fibras. Quanto ao perfil de minerais, o murici é uma boa fonte de potássio (338.58 mg 100 g 1 ), cobre (200 µg 100g ) e magnésio (35.91 mg 100 g 1 ). Os frutos apresentaram 57,41 mg/100 g vitamina C, 308,97 µg/g de luteína, 16,78 µg/g de -caroteno, 3,80 µg/g de -criptoxantina, 6,49 mg/100 g de - tocoferol, 017 mg/100 g de -tocoferol, 2,66 mg/100 g de -tocoferol e 0,33 mg/100 g de -tocoferol. A análise por HPLC-ESI/MS permitiu a identificação de 19 compostos fenólicos nos extratos de murici, sendo três dímeros de proantocianidinas, dois isômeros de catequina, ácido gálico, quercetina e seus derivados, entre outros. Os extratos de murici agiram eficientemente contra os radicais ABTS (TEAC de 158,48 µM Trolox/ g murici fresco para o extrato A e 170,17 para o extrato B), peroxil (1252,88 µM Trolox/ g extrato para o extrato A e 1332,78 para o extrato B), hidroxil (IC = 300,68 µg/mL para o extrato A e 281,33 para o extrato B), superóxido (IC 50 = 374,50 µg/mL para o extrato A e 350,92 para o extrato B). Os extratos inibiram a atividade da enzima xantina oxidase de maneira dose-dependente, porém, foram necessárias altas concentrações. No sistema Rancimat, a adição do extrato A na concentração de 2 mg/mL incrementou o tempo de indução da oxidação em 42,17 por cento , enquanto que o extrato B incrementou em 59,18 por cento . Já no sistema de cooxidação -caroteno/ácido linoleico, 150 µg/mL dos extratos inibiram cerca de 50 por cento da oxidação. Conclusão: Os frutos do murici são fontes potenciais de compostos antioxidantes, os quais atuam como scavengers de radicais livres, inibem a atividade da enzima xantina oxidase e a oxidação de lipídios / Introduction: The murici (Byrsonima crassifolia (L.) Kunth) is a fruit used by the population as food or as a therapeutic agent, but there are few studies about their functional properties. This study aimed to characterize the fruits of murici regarding the composition of antioxidant compounds and to evaluate their mechanisms of antioxidant action in vitro. Methods: The murici were obtained from Araiozes, Maranhão, Brazil. The chemical composition was assessed by official methods of analysis and profile of minerals by optical emission spectrometry with inductively coupled plasma. The analyses of vitamin C, carotenoids and tocoferols were performed by HPLC. Response surface methodology was employed to optimize the extraction of murici phenolics. The optimized conditions were 43.4 per cent acetone for 50.8 min. at 28.9°C (Extract A) and 45.2 per cent acetone for 52.8 min. at 40°C (Extract B). Phenolic compounds of the murici extracts were evaluated by HPLC-ESI/MS and the mechanisms of its antioxidant action were analyzed by in vitro methods. Results: The murici presented (average) 74.35 per cent moisture, 0.68 per cent protein, 1.82 per cent fat, 4.31 per cent carbohydrate and 17.91 per cent fiber. Concerning the profile of minerals, murici is a good source of potassium (338.58 mg 100 g ), copper (200 mg 100g -1 ) and magnesium (35.91 mg 100 g -1 ). The presence of vitamin C (57.41 mg 100g -1 ), lutein (308.97 mg g -1 1 ), -cryptoxanthin (3.80 mg g -1 ), -carotene (16.78 mg g ), -tocopherol (6.49 mg 100 g ), tocopherol (0.17 mg 100 g -1 ), -tocopherol (2.66 mg 100 g ) and tocopherol (0.33 mg 100 g -1 ) was observed in its composition. Nineteen phenolics have been identificated in murici extracts, as three dimers proanthocyanidins, two isomers of catechin, gallic acid, quercetin and their derivatives. Murici extracts acted effectively against radical ABTS (TEAC of 158.48 88 µM Trolox/g fresh murici to extract A and 170.17 to extract B), peroxyl (1252.88 µM Trolox/g extract to extract A and 1332.78 to extract B), hydroxyl (IC = 300.68 µg/mL to extract A and 281.33 to extract B) and superoxide (IC 50 = 374.50 µg/mL for the extract A and 350.92 to extract B). High concentrations of the extracts inhibited the activity of the enzyme xanthine oxidase in a dose-dependent manner. The result found by the Rancimat® method showed that the extract A at 2 mg/mL increased the oxidation induction time 42.17 per cent , while the extract B increased 59.18 per cent . Already in the -carotene/linoleate model system, 150 µg/mL of extracts inhibited the oxidation by 50 per cent . The study still showed that the extract antioxidants may be effective in blocking radical chain reactions and may also interfere with the reactions that produce the secondary products that speed up the systems oxidative process. Conclusion: The murici is potential source of antioxidant compounds, which act as scavengers of free radicals, inhibit the activity of the enzyme xanthine oxidase and lipid oxidation

Crystal engineering is attracting attention in the pharmaceutical industry because the design of new crystal form of drugs can improve their stability, bioavailability and other relevant physical characteristic properties. Therefore, crystal engineering of nutraceuticals such as flavonoids by exploring their hydrogen bonding interactions can generate novel compounds such as pharmaceutical cocrystals. Flavonoids are polyphenolic secondary plant metabolites that are present in varying levels in fruits, vegetables and beverages. The "French paradox", low cardiovascular mortality rate in spite of high intake of saturated fat among the Mediterranean populations made flavonoids an appropriate target for therapeutic researchers. The work herein deals with the crystal engineering of two flavonoids, quercetin and hesperetin, which are already known to exhibit antioxidant properties and reduce cardiovascular effects in humans. However, they have limited bioavailability and poor water solubility. Several new forms of quercetin and hesperetin in the form of solvates and cocrystals were synthesized. These new crystal forms were characterized by various techniques: FT-IR, DSC (Differential Scanning Calorimetry), single X-ray diffraction, powder X-ray diffraction, TGA (Thermal Gravimetric Analysis) and melting point. The new compounds were also studied via dissolution studies performed in 1:1 ethanol/water (V/V%). Thus, crystal engineering proves to be effective way to enhance the solubility and bioavailability of the target flavonoid molecules.

La formation de troubles physico-chimiques pendant le stockage de boissons clarifiées préoccupe la filière cidricole. Ces troubles sont dus à des interactions entre différents constituants de la boisson, générant des agrégats visibles. Ce travail présente un double objectif : étudier la composition des troubles afin de déterminer les familles chimiques impliquées, puis étudier les mécanismes des interactions responsables de l’apparition de ces troubles. Pour cela, la composition des troubles a été analysée dans trois boissons cidricoles (cidre, jus de pomme et pommeau). Les résultats ont montré l’implication des composés phénoliques et ont conduit à l’hypothèse selon laquelle l’oxydation de ces composés jouerait un rôle prépondérant dans leur agrégation. Des protéines ont également été dosées en grandes concentrations dans des troubles de jus de pomme, suggérant leur implication dans leur formation.Ces hypothèses ont été vérifiées par deux approches en solutions modèles : en modèle pommeau et en modèle jus de pomme. Ces travaux ont mis en évidence des troubles de différentes natures en fonction de la boisson étudiée. D’une part, les troubles des cidres et des pommeaux s’expliqueraient essentiellement par l’auto-agrégation des procyanidines oligomères consécutive à leur oxydation. Les marqueurs moléculaires impliqués dans la formation de trouble réversible ont pu être identifiés. D’autre part, les troubles de certains jus de pomme, relativement pauvres en composés phénoliques et riches en protéines, seraient provoqués par la dénaturation de protéines de défense des plantes / Physico-chemical haze appearance during storage of clarified apple-based beverages is a concern for producers. These hazes are caused by interactions between several constituents of the beverage that lead to the formation of visible aggregates. This work had two main goals: analyze the composition of hazes in order to determine which families of compounds are responsible for their formation, and understand which mechanisms are involved. First, the composition of the haze gathered from three apple-based beverages (cider, apple juice and pommeau) was analyzed. The results revealed the implication of phenolic compounds and led to the hypothesis that their oxidation was probably one of the main factors responsible for haze formation. Proteins were found in quite large quantities in some apple juice hazes, which suggests their involvement in haze formation in this beverage.These two hypotheses have been verified using two model approaches: in a model pommeau and in a model apple juice. This work evidenced that different kinds of hazes exist in apple-based beverages. On the one hand, haze in pommeaux and ciders is mainly explained by procyanidin oligomers self-aggregation induced by their oxidation, with possible interactions with other beverage constituents. On the other hand, haze in some apple juices, which probably contain low polyphenol and high protein levels, is triggered by “Pathogenesis-Related Proteins” denaturation that lead to their self-aggregation, in interaction with oligomeric procyanidins.

Plants inherently produce polyphenols (i.e., antioxidants) as a response to reduce oxidative stress caused by abusive environmental pre- and postharvest conditions. These antioxidants, as well as vitamin C, are present in considerable levels in strawberries; however, excessive oxidative stress brought on by improper postharvest handling conditions can reduce the levels of antioxidants in the fruit and shorten the shelf-life of strawberries. Nevertheless, it may be possible to utilize strawberry’s naturally occurring polyphenols to reduce postharvest stress and extend their shelf life. The polyphenolic profile has been previously investigated in several strawberry cultivars, however no studies have determined the unique polyphenolic profiles of three important Florida strawberry cultivars (‘Florida Radiance’, Sweet Sensation® ‘Florida 127’and ‘Florida Beauty’) at harvest and during cold storage. Therefore, in order to better understand the distribution of individual polyphenols within these cultivars and their impact on postharvest shelf-life, this study examined the polyphenolic profiles throughout 7 days of cold storage (1 °C) using an HPLC-DAD. The activity of phenylalanine ammonia lyase (PAL), a key enzyme in the biosynthesis of polyphenols, and polyphenol oxidase (PPO), the enzyme responsible for polyphenol degradation, were also examined during cold storage to understand their possible influences on postharvest synthesis or degradation of polyphenols. This study revealed that the polyphenolic profile of strawberry fruit was genotype dependent; however, pelargonidin 3-glucoside was consistently the anthocyanin found in higher concentrations in the fruit regardless of the cultivar. Apart from the anthocyanins, the flavonols showed the most variation among the three cultivars. PAL was slightly induced during strawberry postharvest storage suggesting that a stress response occurred during cold storage while PPO showed variable induction patterns across all three cultivars most likely due to their different polyphenol profiles. Analysis of the distribution of polyphenols in the cortex and pith of strawberries showed that polyphenols were mostly concentrated in the cortex of the fruit and that the concentration of individual polyphenol in each fruit tissue varied by cultivar. These results indicate that the oxidative stress response varies in each of the strawberry cultivars studied contributing to their unique polyphenolic profile. Results from this study can ultimately help to identify the polyphenols and enzymes related to superior postharvest quality in future studies.

L'angiogenèse est impliquée dans différents processus tels que la cicatrisation, la croissance tumorale et les maladies ischémiques. RhoA, connu pour son implication dans la prolifération et la migration des cellules, est régulé par la voie NO/PKG. Le sildenafil, inhibiteur de la phosphodiestérase 5, permet d'activer cette voie, ce qui constitue une stratégie thérapeutique intéressante dans le traitement des maladies ischémiques. Nous avon montré que le sildenafil améliore la croissance collatérale dès 7 jours de traitement, sans modifier la densité capillaire, via un mécanisme PI3K/akt-NO-dépendant et HIF/VEGF-indépendant. Ces différentes voies sont down-régulées à 21 jours. Enfin cette revascularisation s'accompagne d'un remodelage des artères de résistance, suggérant que le sildenafil favorise non pas l'angiogenèse mais l'artiogenèse. Enfin, nous avons mis en évidence un effet dose-dépendant des polyphenols du vin rouge, un autre puissant vasodilattaeur, sur la revascularisation post-ischémique : à fortes doses les densités vasculaires sont diminuées, associées à une inhibition des voies PI3K/Akt-NO et des MMPs. De faibles doses entraînent une augmentation des densités vasculaires par stimulation des voies PI3K/akt-No, sans affecter les MMPs. Par conséquent, nous avons mis en évidence un effet anti-angiogénique (fortes doses) et un effet pro-angiogenique (faibles doses) des plyphenols. Ce travail nous permet donc de mieux comprendre les mécanismes d'action de deux puissants vasodilatateurs dans revascularisation post-ischémique. Nous pouvons ainsi envisager de nouvelles stratégies thérapeutiques dans le traitement des maladies ischémiques ou du cancer.

Das Metabolische Syndrom stellt eine Kombination verschiedener metabolischer Anomalien in einem Individuum dar. Starkes Übergewicht gilt als maßgebende Größe in der Genese des Syndroms, welches mit einem enormen Risiko für kardiovaskuläre Erkrankungen einhergeht. Um die stark steigende Prävalenz des Metabolischen Syndroms einzudämmen, sind dringend Konzepte für die Behandlung, vor allem jedoch für die Prävention von Übergewicht erforderlich. Einen wichtigen Beitrag leisten diesbezüglich Ballaststoffe in der Ernährung. Sie tragen auf unterschiedlichen Wegen zur Gewichtskontrolle bei und beeinflussen zudem verschiedene mit dem Metabolischen Syndrom assoziierte Blutparameter. Ebenso werden protektive Effekte von Polyphenolen, welche zur Gruppe der sekundären Pflanzenstoffe zählen, beschrieben. Diese wirken u. a. auf den Glukose- sowie den Insulinhaushalt und greifen darüber hinaus in die Regulation der Fettverbrennung sowie des Energieverbrauches ein. Die Kombination beider Substanzgruppen verspricht bedeutendes gesundheitsförderndes Potential; dieses wurde gegenwärtig jedoch kaum untersucht. Carobballaststoff ist ein polyphenolreicher und vorwiegend unlöslicher Extrakt der Frucht des Johannisbrotbaumes (Ceratonia siliqua L). Bislang publizierte Studien zur physiologischen Wirksamkeit dieses Ballaststoffpräparates weisen sowohl beim Tier als auch beim Menschen bemerkenswerte hypocholesterinämische Eigenschaften nach. Inwiefern sich der Verzehr des Carobballaststoffes ebenso auf die Entwicklung von Übergewicht sowie anderen Messgrößen des Metabolischen Syndroms auswirkt, ist allerdings nicht bekannt. Die Zielstellung der Promotionsarbeit bestand darin, die postprandialen Wirkungen des Carobballaststoffverzehrs mit Hilfe einer Humanstudie aufzuzeigen. In die randomisierten, einfach verblindeten Untersuchungen im cross-over-Design wurden 20 gesunde Erwachsene im Alter zwischen 22 und 62 Jahren eingeschlossen. Unter Verwendung variierender Begleitmahlzeiten wurden die postprandialen Effekte verschiedener Mengen des Carobballaststoffes untersucht. Hierbei standen die Veränderungen der Plasmakonzentrationen von Glukose, Triglyceriden (TG), totalem und acyliertem Ghrelin sowie der Serumkonzentrationen von Insulin und nicht-veresterten Fettsäuren (NEFA) im Mittelpunkt der Betrachtungen. Der Verzehr des Carobballaststoffes in Kombination mit 200 ml Wasser und 50 g Glukose erhöhte die postprandialen Glukose- und Insulinkonzentrationen gegenüber der Glukoselösung ohne Ballaststoffzusatz. In Kombination mit 400 ml einer Flüssigmahlzeit verzehrt, senkte Carobballaststoff die postprandialen TG-, NEFA- und Ghrelin- (acyliert) Antworten. Die Untersuchung des respiratorischen Quotienten nach Zusatz von Carobballaststoff zur Flüssigmahlzeit mittels indirekter Respirationskalorimetrie bekräftigte die bereits bekannten Effekte auf den Lipidmetabolismus und wies zudem eine Steigerung der Fettverwertung unter Verminderung der Glukoseoxidation nach. Wurde Carobballaststoff schließlich in Lebensmittel eingebracht, sanken nach dem Verzehr dieser Lebensmittel erneut die postprandialen Konzentrationen an TG und NEFA. Gleichzeitig erhöhten sich die Glukose-, Insulin- sowie Ghrelin- (acyliert) Antworten. Carobballaststoff löst in Abhängigkeit von der jeweils verzehrten Begleitmatrix unterschiedliche Effekte aus. Das Präparat weist beachtliche Wirkungen auf die Blutlipide sowie den Energieverbrauch auf, hat indes ungünstige Wirkungen auf die Blutglukose, sofern er in Kombination mit einer veränderten Nährstoffmatrix aufgenommen wird. Carobballaststoff besitzt starkes gesundheitsförderndes Potential; jedoch sind weitere Studien notwendig, um seine Wirkungen sowie deren Voraussetzungen besser zu verstehen. Ferner sollten Untersuchungen über einen längeren Zeitraum vorgenommen werden, um die langfristige Relevanz der gewonnenen Ergebnisse darzulegen. Danach stellt die Anreicherung spezieller Lebensmittel mit Carobballaststoff einen geeigneten Weg dar, um von den viel versprechenden protektiven Wirkungen des Präparates zu profitieren. / The metabolic syndrome is a clustering of metabolic abnormalities and cardiovascular risk factors that occur in one individual. Since many individuals suffering of the metabolic syndrome are overweight, dietary treatment should primarily focus on weight reduction and control to handle and, much more importantly, to prevent the genesis of the syndrome. Dietary fiber could play a role in the management of the metabolic syndrome through its ability to control body weight as well as several parameters associated to the syndrome. Beside this, dietary polyphenols have been shown to influence glucose and insulin metabolism. Furthermore, studies in mice and men showed that polyphenols might increase fat oxidation and energy expenditure. The combination of both, dietary fiber and polyphenols, may exert beneficial health effects, which are not known up to now. A polyphenol-rich insoluble dietary fiber preparation from carob pulp (Ceratonia siliqua L; carob fiber) showed significant hypocholesterolemic activity in different animal trails and two human studies indicating that carob fiber may have potent health effects. However, short term effects on parameters associated with the control of the metabolic syndrome are not known. Therefore, a study was conducted to investigate the postprandial effects of carob fiber in healthy humans using different background food matrices. The study was designed as a randomized single-blind cross-over study in 20 subjects, aged 22 to 62 years. During several examinations plasma glucose, triglycerides (TG), total and acylated ghrelin, cholecystokinin (CCK) and peptide YY (PYY) as well as serum insulin and non-esterified fatty acids (NEFA) were repeatedly assessed before and after ingestion of carob fiber in combination with different test meals. The study results showed that carob fiber, consumed within a glucose load, increased plasma glucose and serum insulin compared to control. Plasma PYY increased after consumption of carob-enriched glucose solution. In a second part of the study, postprandial changes were assessed before and after ingestion of an isocaloric standardized liquid meal with or without carob fiber. Carob fiber intake lowered acylated ghrelin, triglycerides, and NEFA compared to control meal. Postprandial energy expenditure was increased and RQ was reduced after liquid meal with carob fiber compared to control meal. Finally, effects of the consumption of carob fiber-enriched foods were investigated at the subsequent day. Enrichment of foods increased plasma glucose and acylated ghrelin responses. Plasma triglycerides and serum NEFA responses were lower after bread ingestion compared to control. These results indicate that the effects of polyphenol-rich carob fiber on different blood parameters depend on the meal composition. Carob fiber showed beneficial effects on blood lipids as well as energy homeostasis, but also a deteriorated glycemic control when administered within a different food matrix. Further studies are needed to clarify observed effects and the mechanisms behind. Additionally, present study shows only short-term effects of carob fiber consumption, which might be less pronounced after long-term consumption due to adaptation mechanisms. Thus, future studies should elucidate the relevance of observed effects in long-term.

Dans un contexte de réchauffement climatique, la fonction puits de carbone des tourbières à sphaignes est susceptible d'être altérée en raison d'une modification des interactions sphaignes-microorganismes, responsables de l'accumulation de carbone. L'objectif de cette thèse a été (1) d'identifier les interactions chimiques entre les polyphénols des sphaignes et les communautés microbiennes des sphaignes et (2) d'évaluer l'impact du réchauffement climatique sur ces relations.Un dispositif expérimental (Open Top Chambers) simulant in situ une hausse modérée des températures (+ 1°C) a été installé sur la tourbière de Frasne (25). La hausse des températures a provoqué une modification du réseau alimentaire microbien avec l'augmentation de la biomasse des bactéries et une baisse importante (-70%) de la biomasse des prédateurs (amibes à thèque). Le réchauffement climatique a également induit une baisse de la production de polyphénols, diminuant ainsi leur effet inhibiteur sur les microorganismes. En parallèle à cette baisse, une hausse des activités enzymatiques phénoloxydases a également été enregistrée. Le réchauffement a ainsi modifié les relations polyphénols - phénoloxydases, deux éléments essentiels du cycle du carbone des tourbières.Les différents changements induits par le réchauffement climatique (polyphénols, phénoloxydases, réseau trophique microbien) ont aussi conduit à une modification des relations " sphaignes-microorganismes " via une accélération potentielle du recyclage des nutriments, ce qui pourrait influencer sur le long terme le fonctionnement de l'écosystème tourbière.

Salvia genus is a widely cultivated genus and used in medicine for various purposes as having antimicrobial, antioxidant, anticarcinogen and anti-inflammatory features. In this study the aim was to investigate phenolic composition of Salvia absconditiflora and understand the possible effects of those constituents in cancer related drug metabolizing enzymes. Salvia absconditiflora showed 80,43 % Radical Scavenging Activity against DPPH radical. Total flavonoid content was found as one third of total phenolic content. Presence of important phenolic acids and flavonoids such as caffeic acid, luteolin, coumaric acid are validated with LC-MS/MS analysis. Cytotoxicity of Salvia absconditiflora treatment on MCF-7 and MDA-MB-231 breast cancer cell lines were investigated through XTT and TBE assays both dose and time dependent manner. Cell proliferation was inhibited 50 % by different IC50 values calculated in different assays and different time intervals. This suggests that two breast cancer cell lines response in a different way to cytotoxic treatments. Cancer related drug metabolizing enzyme gene modulations were investigated with qRT-PCR. CYP1A1 and CYP1B1 were upregulated in MCF-7 but down-regulated in MDA-MB-231 cells in response to Salvia absconditiflora treatment.

Salvia genus is a widely cultivated genus and used in medicine for various purposes as having antimicrobial, antioxidant, anticarcinogen and anti-inflammatory features. In this study the aim was to investigate phenolic composition of Salvia absconditiflora and understand the possible effects of those constituents in cancer related drug metabolizing enzymes. Salvia absconditiflora showed 80,43 % Radical Scavenging Activity against DPPH radical. Total flavonoid content was found as one third of total phenolic content. Presence of important phenolic acids and flavonoids such as caffeic acid, luteolin, coumaric acid are validated with LC-MS/MS analysis. Cytotoxicity of Salvia absconditiflora treatment on MCF-7 and MDA-MB-231 breast cancer cell lines were investigated through XTT and TBE assays both dose and time dependent manner. Cell proliferation was inhibited 50 % by different IC50 values calculated in different assays and different time intervals. This suggests that two breast cancer cell lines response in a different way to cytotoxic treatments. Cancer related drug metabolizing enzyme gene modulations were investigated with qRT-PCR. CYP1A1 and CYP1B1 were up-regulated in MCF-7 but down-regulated in MDA-MB-231 cells in response to Salvia absconditiflora treatment.

L'objectiu d'aquesta tesi doctoral és avaluar els efectes de les fraccions del vi (alcohòlica i no alcohòlica -principalment polifenols-) sobre els principals factors de risc cardiovascular en 67 homes amb un elevat risc de patir malalties cardiovasculars. Es va realitzar un assaig clínic, aleatoritzat i creuat en el qual tots els participants van rebre en un ordre aleatori les tres intervencions: 30 gr d'alcohol / dia en forma de vi negre, la mateixa quantitat de polifenols en forma de vi negre desalcoholitzat i 30gr d'alcohol / dia en forma de ginebra, durant 28 dies cada intervenció. Es van avaluar els efectes al final de cada una de les tres intervencions sobre els biomarcadors cel•lulars i sèrics d’inflamació relacionats amb l'aterosclerosi, el metabolisme glucídic, el perfil lipídic i la pressió arterial. El consum moderat d'alcohol (intervencions amb vi negre i ginebra) van incrementar la interleucina (IL) -10 i van disminuir la monocyte-derived chemoquine (MDC). Els polifenols del vi negre (intervencions amb vi negre i vi negre desalcoholitzat) van disminuir les concentracions sèriques de la intercellular adhesion molecule (ICAM) -1, E-selectina i IL-6, i també inhibiren l'expressió del lymphocyte function-associated antigen 1 ( LFA-1) en els limfòcits T i la de Mac -1, SLex (CD15) i CCR2 en la superfície dels monòcits. Tant l'etanol com els polifenols del vi negre varen disminuir les concentracions circulants de l’antigen i el lligand del CD40, CD40, IL-16, monocyte chemoprotein (MCP) -1 i vascular cellular adhesion molecule (VCAM) -1. La concentració de glucosa en dejú es va mantenir constant al llarg de l'estudi, mentre que la concentració d'insulina plasmàtica i, en conseqüència, l'índex HOMA va disminuir després del vi negre i el vi negre desalcoholitzat. El colesterol HDL, l'apolipoproteïna AI i A-II van augmentar després de les intervencions amb vi negre i ginebra. La lipoproteïna (a) plasmàtica només va disminuir després de la intervenció amb vi negre. A més, la pressió sistòlica i diastòlica només van disminuir significativament després de la intervenció amb vi negre desalcoholitzat, canvis correlacionats amb un augment de la concentració plasmàtica d'òxid nítric. La pressió sistòlica i diastòlica van disminuir i l'òxid nítric va augmentar, encara que no significativament, després de la intervenció amb vi negre i també comparat amb la ginebra encara que tampoc significativament. El consum moderat de ginebra no va tenir cap efecte en la pressió arterial ni en la concentració plasmàtica d'òxid nítric. Per tant, els polifenols del vi negre disminueixen l'expressió de molècules d'adhesió leucocitàries i la pressió arterial, així com també milloren la resistència a la insulina mentre que tant l'alcohol com els polifenols del vi negre modulen els mediadors inflamatoris solubles en homes d'alt risc cardiovascular, conferint al vi negre més efectes protectors sobre la patologia cardiovascular que altres begudes alcohòliques. / "Benefit / risk balance of polyphenols and alcohol content of wine: scientific basis of the effects of moderate wine consumption on the cardiovascular system" The objective of this thesis is to evaluate the effects of the fractions of the wine (alcoholic and non-alcoholic, mainly polyphenols) on major cardiovascular risk factors in 67 men with at high risk of cardiovascular disease. We performed a clinical, randomized, crossover in which all participants received in a random order the following three interventions: 30 g alcohol / day as red wine, the equivalent amount of dealcoholized red wine and 30g alcohol / day as gin, for 28 days each intervention. The effects at the end of the three interventions on serum and cellular biomarkers of inflammation associated with atherosclerosis, glucose metabolism, lipid profile and blood pressure were evaluated. Moderate consumption of alcohol (red wine interventions and gin) increased interleukin (IL) -10 and decreased monocyte-derived chemoquine (MDC). Polyphenols in red wine (red wine and dealcoholized red wine interventions) decreased serum concentrations of intercellular adhesion molecule (ICAM) -1, E-selectin and IL-6, and inhibited the expression of lymphocyte function-associated antigen 1 ( LFA-1) on T lymphocytes and Mac -1, sLex (CD15) and CCR2 on the surface of monocytes. Both ethanol and wine polyphenols decreased circulating levels of CD40a, CD40L, IL-16, monocyte chemoprotein (MCP) -1 and vascular cellular adhesion molecule (VCAM) -1. The fasting blood glucose concentration was constant throughout the study, whereas the concentration of plasma insulin and consequently the HOMA index decreased after the red wine and the dealcoholized red wine interventions. HDL cholesterol, apolipoprotein AI and A-II increased after the intervention with red wine and gin. Lipoprotein(a) decreased only after the intervention with red wine. Moreover, the systolic and diastolic pressure significantly decreased only after the intervention with dealcoholized red wine, changes correlated with an increased plasma concentration of nitric oxide. In conclusion, red wine polyphenols modulate the expression of leukocyte adhesion molecules, insulin resistance and blood pressure, while both alcohol and red wine polyphenols modulate the soluble inflammatory mediators in men at high cardiovascular risk, conferring to red wine greater protective effects on cardiovascular diseases than other alcoholic beverages.