RESUMO
BACKGROUND: While the bioavailability of cocoa polyphenols, particularly of the monomer (-)-epicatechin, has been investigated after a single-dose intake, the effect of sustained cocoa consumption on the metabolic profile of the structurally related (-)-epicatechin metabolites (SREMs) has not been investigated. METHODS: A randomized, controlled crossover clinical trial in healthy young adults (18-40 year) was conducted to evaluate SREMs after consumption of a single-dose and after daily consumption of 1.3 g of polyphenol-rich cocoa powder for 28 days. The circulating SREMs were measured by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). RESULTS: Twenty subjects (eleven males and nine females) were enrolled. The SREMs concentrations increased to 1741 ± 337 nM after a single-dose and to 1445 ± 270 nM after sustained supplementation. Sulfate conjugates showed higher levels in females (p < 0.05). The epicatechin-3'-glucuronide (E3'G) and epicatechin-3'-sulfate (E3'S) were the most abundant metabolites in all subjects. A high intra-individual correlation (r = 0.72, p < 0.001) between SREMs concentrations after single-dose and sustained supplementation was observed. The antioxidant capacity of plasma did not change in response to the intervention and was not correlated with any of the SREMs. CONCLUSION: The individual SREMs profile and concentrations after a 28-day supplementation are comparable to those after a single dose.
Assuntos
Catequina/sangue , Chocolate , Suplementos Nutricionais , Ingestão de Alimentos/fisiologia , Polifenóis/administração & dosagem , Adolescente , Adulto , Disponibilidade Biológica , Catequina/análogos & derivados , Cromatografia Líquida de Alta Pressão , Estudos Cross-Over , Feminino , Voluntários Saudáveis , Humanos , Masculino , Espectrometria de Massas em Tandem , Adulto JovemRESUMO
Grape pomace extract (GPE) is a rich and relatively low-cost source of phenolic compounds. However, little is known about the main GPE metabolites in mammals, which could help explain the observed health-promoting effects. This study investigated the presence of parent compounds from flavanol, flavonol and stilbene families and their metabolites in rat plasma and tissues after an acute intake of GPE in doses of 300 and 600â¯mgâ¯kg/body weight. The measurement of free compounds and their metabolites was performed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Results showed the presence of epicatechin, epicatechin methyl-glucuronide, epicatechin methyl-sulphate, catechin, catechin-glucuronide, quercetin methyl-glucuronide, resveratrol-3-glucuronide, resveratrol-4-glucuronide and resveratrol-3-sulphate in plasma, which was dose dependent. The most abundant measured compound in plasma was epicatechin-glucuronide. The presence of glucuronidated and methyl-glucuronidated forms of catechin were observed in the liver at both doses, while epicatechin-glucuronide and methyl-glucuronide were detected only upon intake of 600â¯mg GPE/kg body weight. At this dose epicatechin-glucuronide and methyl-glucuronide were also detected in muscle, and catechin methyl-glucuronide in adipose tissue. Results show the main GPE metabolites present in rat tissues after oral consumption, contributing to better understand the health benefits of GPE and its potential utilization as a functional ingredient.
Assuntos
Flavonoides/sangue , Flavonoides/metabolismo , Fenóis/sangue , Fenóis/metabolismo , Extratos Vegetais/metabolismo , Vitis/metabolismo , Animais , Catequina/análise , Catequina/sangue , Catequina/metabolismo , Cromatografia Líquida de Alta Pressão , Flavonoides/análise , Masculino , Fenóis/análise , Extratos Vegetais/administração & dosagem , Quercetina/análise , Quercetina/sangue , Quercetina/metabolismo , Ratos Wistar , Resveratrol/análise , Resveratrol/sangue , Resveratrol/metabolismo , Espectrometria de Massas em TandemRESUMO
We assessed the effects of guaraná (Paullinia cupana) consumption on plasma catechins, erythrocyte antioxidant enzyme activity (superoxide dismutase, catalase and glutathione peroxidase) and biomarkers of oxidative stress (ex vivo LDL oxidation, plasma total antioxidant status and ORAC, and lymphocyte single cell gel electrophoresis) in healthy overweight subjects. Twelve participants completed a 15-day run-in period followed by a 15-day intervention with a daily intake of 3 g guaraná seed powder containing 90 mg (+)-catechin and 60 mg (-)-epicatechin. Blood samples were taken on the first and last day of the intervention period, fasting and 1 h post-dose. The administration of guaraná increased plasma ORAC, while reducing ex vivo LDL oxidation (only in the first study day) and hydrogen peroxide-induced DNA damage in lymphocytes, at 1 h post-dose. Plasma catechin (0.38 ± 0.12 and 0.44 ± 0.18 nmol mL(-1)), epicatechin (0.59 ± 0.18 and 0.64 ± 0.25 nmol mL(-1)) and their methylated metabolites were observed at 1 h post-dose but were almost negligible after overnight fasting. The activities of catalase (in both study days) and glutathione peroxidase (in the last intervention day) increased at 1 h post-dose. Furthermore, the activity of both enzymes remained higher than the basal levels in overnight-fasting individuals on the last intervention day, suggesting a prolonged effect of guaraná that continues even after plasma catechin clearance. In conclusion, guaraná catechins are bioavailable and contribute to reduce the oxidative stress of clinically healthy individuals, by direct antioxidant action of the absorbed phytochemicals and up-regulation of antioxidant/detoxifying enzymes.
Assuntos
Antioxidantes/metabolismo , Biomarcadores/sangue , Catequina/farmacocinética , Estresse Oxidativo/efeitos dos fármacos , Paullinia/química , Adulto , Antropometria , Catalase/sangue , Catequina/administração & dosagem , Catequina/sangue , Colesterol/sangue , Dano ao DNA/efeitos dos fármacos , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Jejum , Feminino , Glutationa Peroxidase/sangue , Humanos , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Sobrepeso/sangue , Sobrepeso/tratamento farmacológico , Sementes/química , Superóxido Dismutase/sangue , Triglicerídeos/sangueRESUMO
Cocoa is rich in flavonoids, which are potent antioxidants with established benefits for cardiovascular health but unproven effects on neurodegeneration. Sirtuins (SIRTs), which make up a family of deacetylases, are thought to be sensitive to oxidation. In this study, the possible protective effects of cocoa in the diabetic retina were assessed. Rat Müller cells (rMCs) exposed to normal or high glucose (HG) or H2O2 were submitted to cocoa treatment in the presence or absence of SIRT-1 inhibitor and small interfering RNA The experimental animal study was conducted in streptozotocin-induced diabetic rats randomized to receive low-, intermediate-, or high-polyphenol cocoa treatments via daily gavage for 16 weeks (i.e., 0.12, 2.9 or 22.9 mg/kg/day of polyphenols). The rMCs exposed to HG or H2O2 exhibited increased glial fibrillary acidic protein (GFAP) and acetyl-RelA/p65 and decreased SIRT1 activity/expression. These effects were cancelled out by cocoa, which decreased reactive oxygen species production and PARP-1 activity, augmented the intracellular pool of NAD(+), and improved SIRT1 activity. The rat diabetic retinas displayed the early markers of retinopathy accompanied by markedly impaired electroretinogram. The presence of diabetes activated PARP-1 and lowered NAD(+) levels, resulting in SIRT1 impairment. This augmented acetyl RelA/p65 had the effect of up-regulated GFAP. Oral administration of polyphenol cocoa restored the above alterations in a dose-dependent manner. This study reveals that cocoa enriched with polyphenol improves the retinal SIRT-1 pathway, thereby protecting the retina from diabetic milieu insult.
Assuntos
Cacau/química , Retinopatia Diabética/prevenção & controle , Proteína Glial Fibrilar Ácida/metabolismo , Polifenóis/farmacologia , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/farmacologia , Catequina/sangue , Cromatografia Líquida , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/prevenção & controle , Relação Dose-Resposta a Droga , Proteína Glial Fibrilar Ácida/genética , Glucose/metabolismo , Peróxido de Hidrogênio/metabolismo , Masculino , Neuroglia/efeitos dos fármacos , Neuroglia/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Endogâmicos SHR , Espécies Reativas de Oxigênio/metabolismo , Retina/efeitos dos fármacos , Retina/metabolismo , Transdução de Sinais , Sirtuína 1/genética , Sirtuína 1/metabolismo , Estreptozocina/efeitos adversos , Espectrometria de Massas em Tandem , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismoRESUMO
Based on the recognized capacity of (+)-catechin (CTCH) to prevent free radical-mediated damage in different biological systems, its role in the protection of human plasma from oxidation was investigated. Samples of human blood plasma were incubated with 50 mM AAPH [2,2'-azobis-(2-amidinopropane) clorhidrate] or AMVN [2,2'-azobis(2,4-valeronitrile)], in the absence or the presence of CTCH (0.01 to 1 mM). Lipid oxidation was evaluated measuring the formation of 2-thiobarbituric acid reactive substances (TBARS). Alpha-tocopherol (AT), beta-carotene (BC), and CTCH were measured by reverse phase HPLC with electrochemical detection. TBARS formation was dependent on incubation time and on the nature of the azocompound, yielding 4.8 +/- 0.9, and 14.9 +/- 3.4 microM MDA, after 4 h, in AAPH and AMVN-exposed plasma, respectively. Plasma AT and BC were extensively depleted under these oxidant conditions. The addition of CTCH prevented or delayed the formation of TBARS, and the depletion of AT and BC in a dose dependent manner. This antioxidant effect was dependent on the concentration of CTCH and on the physical characteristics of the radical initiator. CTCH supplementation modified not only the lag time for the antioxidants depletion, but also the consumption rate. These results indicate that CTCH was an effective antioxidant in human blood plasma, delaying the consumption of endogenous lipid soluble antioxidants (AT and BC) and inhibiting lipid oxidation.