Trans-resveratrol inhibits early blood vessel formation (Vasculogenesis) without impairment of embryonic growth

Resveratrol is a stilbene compound found in grapes and other sources. In this study we examined the effects of trans-resveratrol (4.38-438 mu M/implant) in the vasculogenesis of yolk-sac membranes and its capacity to improve chick embryo growth. High concentrations of the stilbene (43.8-438 mu M) significantly inhibited early vessel formation, decreasing the percentage vitelline vessels of 3.5-day embryos by 50% compared to the control. In addition, basic fibroblast growth factor-stimulated vasculogenesis (140% of vessels as compared to control) was partially reversed by t-resveratrol (35% of inhibition) and treatments with cyclooxygenase inhibitors (acetylsalicylic acid and indomethacin) as well a protein-kinase C (PKC) activator (phorbol-12,13-dibutyrate) decreased the vessel number to 60%, 50%, and 44%, respectively. Treatments with t-resveratrol (4.38-43.8 mu M/implant) significantly increased the body length of embryos incubated in vitro uncoupled from any impairment in the body shape or detectable embryotoxic effect. We suggest that the antivasculogenic activity and the enhancement in embryonic growth promoted by non acute treatments with t-resveratrol were, at least in part, due to PKC inhibition. We suggest that t-resveratrol can be usable not only as a reliable functional nutriment, but also is useful for the development of prophylactic and/or therapeutic agents for treatment of angiogenic-degenerative diseases.

Síntese de trans-resveratrol e controle de podridão em maçãs com uso de elicitores em pós-colheita

O objetivo deste trabalho foi avaliar o efeito da aplicação de elicitores abióticos na biossíntese de resveratrol e na indução de resistência à podridão póscolheita de maçãs 'Gala' e 'Fuji'. Foram realizados os tratamentos: radiação ultravioleta, fosfito e acibenzolar-Smetil - aplicados antes do armazenamento - e ozônio - aplicado intermitente durante o armazenamento. As condições de armazenamento foram: 'Gala', 1,5 kPa de O2 e 2,5 kPa de CO2, a 0,5±0,1ºC, por oito meses, e 'Fuji', 1,0 kPa de O2 e <0,5 kPa de CO2, a 0,5±0,1ºC, por sete meses. O delineamento experimental foi inteiramente ao acaso, com oito repetições de 25 frutos. Na casca dos frutos, determinou-se: trans-resveratrol, polifenóis totais, antocianinas totais e diâmetro de lesão, após inoculação de Penicillium sp. no ferimento. Analisou-se na polpa: firmeza de polpa, acidez titulável, sólidos solúveis totais, açúcares redutores e nãoredutores. Os elicitores não alteram a concentração de polifenóis totais e antocianinas, com exceção do acibenzolar-Smetil que reduz o conteúdo de antocianinas na maçã 'Gala'. Os elicitores induzem, na 'Fuji', mas não na maçã 'Gala', a síntese de trans-resveratrol na seqüência: acibenzolar-Smetil> fosfito> irradiação UV-C> ozônio. Na maçã 'Gala', o fosfito reduz a ocorrência de podridão, porém, em ambas as cultivares, não há correlação entre síntese de trans-resveratrol e controle de podridão.

Distribution of [H-3]trans-resveratrol in rat tissues following oral administration

Resveratrol has been widely investigated for its potential health properties, although little is known about its metabolism in vivo. Here we investigated the distribution of metabolic products of [H-3]trans-resveratrol, following gastric administration. At 2 h, plasma concentrations reached 1 center dot 7 % of the administered dose, whilst liver and kidney concentrations achieved 1 center dot 0 and 0 center dot 6 %, respectively. Concentrations detected at 18 h were lower, being only 0 center dot 5 % in plasma and a total of 0 center dot 35 % in tissues. Furthermore, whilst kidney and liver concentrations fell to 10 and 25 %, respectively, of concentrations at 2 h, the brain retained 43 % of that measured at 2 h. Resveratrol-glucuronide was identified as the major metabolite, reaching 7 mu m in plasma at 2 h. However, at 18 h the main form identified in liver, heart, lung and brain was native resveratrol aglycone, indicating that it is the main form retained in the tissues. No phenolic degradation products were detected in urine or tissues, indicating that, unlike flavonoids, resveratrol does not appear to serve as a substrate for colonic microflora. The present study provides additional information about the nature of resveratrol metabolites and which forms might be responsible for its in vivo biological effects.

Efeito do trans-resveratrol sobre a longevidade e o metabolismo de glicogênio de Drosophila melanogaster em diferentes idades

O trans-resveratrol é uma fitoalexina natural encontrada em uvas, amoras, amendoim e muitas espécies de plantas. Em uvas o trans-resveratrol é responsável pela proteção natural contra doenças e sua concentração depende da origem geográfica, da variedade e dos métodos de fabricação do vinho; sendo considerado por muitos autores como um geroprotetor. O objetivo do presente trabalho foi verificar o efeito do transresveratrol na longevidade e no metabolismo de carboidratos (glicogênio, atividade e expressão da enzima glicogênio fosforilase - GFT) de Drosophila melanogaster em diferentes idades (0, 7, 14, 18 e 21 dias). Para a análise da longevidade espécimes de D. melanogaster com idade de 10 dias foram colocados em vidros contendo meio de cultura padrão acrescido de água ou dimetilsulfóxido (DMSO) 0,03%, ou trans-resveratrol nas concentrações de 1, 10 ou 20μM para ovoposição durante 24 horas, a prole recebeu os seus respectivos tratamentos durante toda a vida. Para as análises do metabolismo de glicogênio os espécimes de D. melanogaster foram colocados em meio de cultura padrão adicionado de água ou dimetilsulfóxido 0,03% (DMSO) ou ainda, trans-resveratrol na concentração de 1μM dissolvido em DMSO (0,03%) para ovoposição; seus ovos foram mantidos até a eclosão, durante a fase adulta os animais continuaram a receber os seus respectivos tratamentos até os pontos em que foram feitas as determinações bioquímicas e moleculares. Os resultados indicam que o tratamento com trans-resveratrol modulou o metabolismo de carboidratos em fêmeas e em machos de forma diferenciada; contudo, este composto não foi capaz de alterar a expressão gênica da GFT. Nas fêmeas tratadas com trans-resveratrol 1μM verificou-se um aumento de 127% na longevidade quando comparado ao grupo controle. Já nos machos tratados com trans-resveratrol 1μM observou-se um acréscimo de 50% na longevidade quando comparado ao grupo controle. Em ambos sexos tratados com Trans-resveratrol 10 e 20μM não houve aumento significativo da longevidade. Com base nos resultados podemos sugerir que o trans-resveratrol como outros antioxidantes descritos na literatura tem seus efeitos benéficos na menor dose administrada, podendo nas doses mais elevadas estar atuando como um pró-oxidante. Os resultados obtidos sugerem que o trans-resveratrol modula o metabolismo do glicogênio tanto em machos como em fêmeas e aumenta a longevidade do modelo experimental testado.

Avaliação do potencial de carreadores lipídicos nanoestruturados para a administração cutânea de trans-resveratrol

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Incorporação do trans-resveratrol em sistemas nanoestruturados: avaliação das ações antioxidante e despigmentante in vitro

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Desenvolvimento e caracterização de nanopartículas lipídicas sólidas para administração cutânea de trans-resveratrol

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Determinação de resveratrol e características químicas em sucos de uvas produzidas em sistemas orgânico e convencional

O presente estudo avaliou os teores de trans-resveratrol e algumas características químicas: acidez total titulável (ATT), sólidos solúveis totais (SST) e relação SST/ATT, em amostras de sucos de uvas da variedade Concorde e Rúbea, sobre o porta-enxerto Campinas IAC 766, produzidas em sistemas orgânico e convencional. O suco foi obtido pelo método de cocção de uvas sadias e maduras. Os resultados encontrados para os sucos de uvas das variedades Concorde e Rúbea, sobre o porta-enxerto Campinas IAC 766, orgânico e convencional, apresentaram concentração de trans-resveratrol de 25,9; 27,2; 32,5 e 32,9 mg L-1, respectivamente. No suco das variedades Concorde e Rúbea de produção orgânica foram obtidos os valores de 0,77 e 0,91 g de ácido tartárico 100 mL-1. Para as mesmas variedades produzidas em sistema convencional 0,94 e 0,75 g de ácido tartárico 100 mL-1. Os valores observados para SST e SST/ ATT para as variedades de sistemas orgânico e convencional foram 10,95; 11,73; 14,23; e 13,23 ºBrix e 14,22; 12,64; 15,18; e 17,64, respectivamente. Das avaliações realizadas com relação ao trans-resveratrol pode-se concluir que as variedades, independentemente do sistema de cultivo, são fontes de resveratrol e que os sucos podem ser consumidos como alimento funcional.

Concentrations of resveratrol and derivatives in foods and estimation of dietary intake in a Spanish population: European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort

Resveratrol has been shown to have beneficial effects on diseases related to oxidant and/or inflammatory processes and extends the lifespan of simple organisms including rodents. The objective of the present study was to estimate the dietary intake of resveratrol and piceid (R&P) present in foods, and to identify the principal dietary sources of these compounds in the Spanish adult population. For this purpose, a food composition database (FCDB) of R&P in Spanish foods was compiled. The study included 40 685 subjects aged 35–64 years from northern and southern regions of Spain who were included in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort. Usual food intake was assessed by personal interviews using a computerised version of a validated diet history method. An FCDB with 160 items was compiled. The estimated median and mean of R&P intake were 100 and 933 μg/d respectively. Approximately, 32 % of the population did not consume R&P. The most abundant of the four stilbenes studied was trans-piceid (53·6 %), followed by trans-resveratrol (20·9 %), cis-piceid (19·3 %) and cis-resveratrol (6·2 %). The most important source of R&P was wines (98·4 %) and grape and grape juices (1·6 %), whereas peanuts, pistachios and berries contributed to less than 0·01 %. For this reason the pattern of intake of R&P was similar to the wine pattern. This is the first time that R&P intake has been estimated in a Mediterranean country.

Resveratrol: A polyphenol with multiple effects

trans-Resveratrol (trans-3,5,4'-trihydroxystilbene) is a natural polyphenol that occurs in grapes, berries, peanuts, and several traditional medicines. A number of studies have demonstrated that this polyphenol holds promise against numerous age-associated diseases including cancer, diabetes, Alzheimer, cardiovascular and pulmonary diseases. In view of these studies, resveratrol's prospects for use in the clinics are rapidly accelerating. This review summarizes our work on the mechanisms involved in the intestinal absorption and its population pharmacokinetics. Finally, various targets of resveratrol and its therapeutic potential are described.

Concentrations of resveratrol and derivatives in foods and estimation of dietary intake in a Spanish population: European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort

Resveratrol has been shown to have beneficial effects on diseases related to oxidant and/or inflammatory processes and extends the lifespan of simple organisms including rodents. The objective of the present study was to estimate the dietary intake of resveratrol and piceid (R&P) present in foods, and to identify the principal dietary sources of these compounds in the Spanish adult population. For this purpose, a food composition database (FCDB) of R&P in Spanish foods was compiled. The study included 40 685 subjects aged 3564 years from northern and southern regions of Spain who were included in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort. Usual food intake was assessed by personal interviews using a computerised version of a validated diet history method. An FCDB with 160 items was compiled. The estimated median and mean of R&P intake were 100 and 933 mg/d respectively. Approximately, 32% of the population did not consume RΠ The most abundant of the four stilbenes studied was trans-piceid (53·6 %), followed by trans-resveratrol (20·9 %), cis-piceid (19·3 %) and cis-resveratrol (6·2 %). The most important source of R&P was wines (98·4 %) and grape and grape juices (1·6 %), whereas peanuts, pistachios and berries contributed to less than 0·01 %. For this reason the pattern of intake of R&P was similar to the wine pattern. This is the first time that R&P intake has been estimated in a Mediterranean country.

Concentrations of resveratrol and derivatives in foods and estimation of dietary intake in a Spanish population: European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort

Resveratrol has been shown to have beneficial effects on diseases related to oxidant and/or inflammatory processes and extends the lifespan of simple organisms including rodents. The objective of the present study was to estimate the dietary intake of resveratrol and piceid (R&P) present in foods, and to identify the principal dietary sources of these compounds in the Spanish adult population. For this purpose, a food composition database (FCDB) of R&P in Spanish foods was compiled. The study included 40 685 subjects aged 35-64 years from northern and southern regions of Spain who were included in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Spain cohort. Usual food intake was assessed by personal interviews using a computerised version of a validated diet history method. An FCDB with 160 items was compiled. The estimated median and mean of R&P intake were 100 and 933 mg/d respectively. Approximately, 32% of the population did not consume RΠ The most abundant of the four stilbenes studied was trans-piceid (53·6 %), followed by trans-resveratrol (20·9 %), cis-piceid (19·3 %) and cis-resveratrol (6·2 %). The most important source of R&P was wines (98·4 %) and grape and grape juices (1·6 %), whereas peanuts, pistachios and berries contributed to less than 0·01 %. For this reason the pattern of intake of R&P was similar to the wine pattern. This is the first time that R&P intake has been estimated in a Mediterranean country.

Determinação de resveratrol em sucos de uva no Brasil

A detecção de resveratrol em vinhos vem sendo estudada mais intensamente nos últimos anos. O isômero trans-resveratrol tem reconhecidas atividades biológicas, e algumas delas são de uso terapêutico, tais como ação antiinflamatória, inibição da enzima lipoxigenase e ação anticarcinogênica in vitro. A presença do composto resveratrol (4,3',5'-trihidroxiestilbeno), em seus isômeros (trans e cis), foi determinada nos diferentes tipos de sucos de uva produzidos no Brasil. Além destes, também foram quantificados os polifenóis totais, acidez, açúcares redutores, sólidos solúveis e densidade, em conformidade com a legislação vigente. O resveratrol foi quantificado por cromatografia líquida de alta eficiência segundo SOUTO et al. [23], com adaptação da temperatura para 50° C. Foi detectada a presença de trans-resveratrol em todos os sucos analisados na concentração de 0,19mg.L-1 a 0,90mg.L-1 e o isômero cis-resveratrol foi de 0,07 a 1,59mg.L-1 .

Resveratrol reduces myofibroblast arrhythmogenicity

Background: Among grape skin polyphenols, trans-resveratrol (RES) has been reported to slow the development of cardiac fibrosis and to affect myofibroblast (MFB) differentiation. Because MFBs induce slow conduction and ectopic activity following heterocellular gap junctional coupling to cardiomyocytes, we investigated whether RES and its main metabolites affect arrhythmogenic cardiomyocyte-MFB interactions. Methods: Experiments were performed with patterned growth strands of neonatal rat ventricular cardiomyocytes coated with cardiac MFBs. Impulse propagation characteristics were measured optically using voltage-sensitive dyes. Long-term video recordings served to characterize drug-related effects on ectopic activity. Data are given as means ± S.D. (n = 4–20). Results: Exposure of pure cardiomyocyte strands to RES at concentrations up to 10 µmol/L had no significant effects on impulse conduction velocity (θ) and maximal action potential upstroke velocities (dV/dtmax). By contrast, in MFB-coated strands exhibiting slow conduction, RES enhanced θ with an EC50 of ~10 nmol/L from 226 ± 38 to 344 ± 24 mm/s and dV/dtmax from 48 ± 7 to 69 ± 2%APA/ms, i.e., to values of pure cardiomyocyte strands (347 ± 33 mm/s; 75 ± 4%APA/ms). Moreover, RES led to a reduction of ectopic activity over the course of several hours in heterocellular preparations. RES is metabolized quickly in the body; therefore, we tested the main known metabolites for functional effects and found them similarly effective in normalizing conduction with EC50s of ~10 nmol/L (3-OH-RES), ~20 nmol/L (RES-3-O-β-glucuronide) and ~10 nmol/L (RES-sulfate), respectively. At these concentrations, neither RES nor its metabolites had any effects on MFB morphology and α-smooth muscle actin expression. This suggests that the antiarrhythmic effects observed were based on mechanisms different from a change in MFB phenotype. Conclusions: The results demonstrate that RES counteracts MFB-dependent arrhythmogenic slow conduction and ectopic activity at physiologically relevant concentrations. Because RES is rapidly metabolized following intestinal absorption, the finding of equal antiarrhythmic effectiveness of the main RES metabolites warrants their inclusion in future studies of potentially beneficial effects of these substances on the heart.

Determinação da actividade antioxidante e composição fenólica de vinhos portugueses e correlação com parâmetros de cor

Dissertação para obtenção do Grau de Mestre em Tecnologia e Segurança Alimentar – Qualidade Alimentar