RESUMO
Advanced Glycation End-products (AGEs) have been associated to diabetes, neurodegenerative and cardiovascular diseases. Mitigating the formation of AGEs is a strategy to avoid detrimental physiopathological effects of age-related chronic diseases. An olive leaf extract (OLE), obtained under acidic conditions, and two fractions, obtained by solid-phase extraction, were characterized by LC-MS/MS. Antiglycative capacity of OLE and fractions were investigated in different in vitro models. The OLE significantly inhibited the formation of Amadori products at the early stage as well as the formation of fluorescent AGEs at the advanced stage of the glycation. Carboxymethyllysine was significantly inhibited by the OLE but it showed weaker activity against argpyrimidine and carboxyethyllysine. The antiglycative activity of each OLE fraction independently did not explain the activity reached in the whole extract, being necessary the compounds present in both fractions. OLE and its fractions were highly effective for trapping reactive dicarbonyl compounds (glyoxal, methylglyoxal, 3-deoxyglucosone and 3-deoxygalactosone). Different adducts resulting from the conjugation of methylglyoxal and hydroxytyrosol in OLE were identified. Results pointed out that OLE exert a broad-spectrum in vitro antiglycative activity.
Assuntos
Olea/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Cromatografia Líquida , Desoxiglucose/análogos & derivados , Desoxiglucose/metabolismo , Frutosamina/antagonistas & inibidores , Frutosamina/metabolismo , Galactose/análogos & derivados , Galactose/metabolismo , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Produtos Finais de Glicação Avançada/metabolismo , Glicosilação , Glioxal/metabolismo , Lisina/análogos & derivados , Lisina/antagonistas & inibidores , Lisina/metabolismo , Ornitina/análogos & derivados , Ornitina/antagonistas & inibidores , Ornitina/metabolismo , Fenóis/farmacologia , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/metabolismo , Pirimidinas/antagonistas & inibidores , Pirimidinas/metabolismo , Aldeído Pirúvico/metabolismo , Espectrometria de Massas em TandemRESUMO
Herein, we investigated the hypoglycemic effect of plant gallic acid (GA) on glucose uptake in an insulin-resistant cell culture model and on hepatic carbohydrate metabolism in rats with a high-fructose diet (HFD)-induced diabetes. Our hypothesis is that GA ameliorates hyperglycemia via alleviating hepatic insulin resistance by suppressing hepatic inflammation and improves abnormal hepatic carbohydrate metabolism by suppressing hepatic gluconeogenesis and enhancing the hepatic glycogenesis and glycolysis pathways in HFD-induced diabetic rats. Gallic acid increased glucose uptake activity by 19.2% at a concentration of 6.25 µg/mL in insulin-resistant FL83B mouse hepatocytes. In HFD-induced diabetic rats, GA significantly alleviated hyperglycemia, reduced the values of the area under the curve for glucose in an oral glucose tolerance test, and reduced the scores of the homeostasis model assessment of insulin resistance index. The levels of serum C-peptide and fructosamine and cardiovascular risk index scores were also significantly decreased in HFD rats treated with GA. Moreover, GA up-regulated the expression of hepatic insulin signal transduction-related proteins, including insulin receptor, insulin receptor substrate 1, phosphatidylinositol-3 kinase, Akt/protein kinase B, and glucose transporter 2, in HFD rats. Gallic acid also down-regulated the expression of hepatic gluconeogenesis-related proteins, such as fructose-1,6-bisphosphatase, and up-regulated expression of hepatic glycogen synthase and glycolysis-related proteins, including hexokinase, phosphofructokinase, and aldolase, in HFD rats. Our findings indicate that GA has potential as a health food ingredient to prevent diabetes mellitus.