Treatment of NASH with Antioxidant Therapy: Beneficial Effect of Red Cabbage on Type 2 Diabetic Rats.

AIMS: Oxidative stress (OS) plays a major role in type 2 diabetes and its vascular and hepatic complications, and novel therapeutic approaches include natural antioxidants. Our previous chemical and biological studies demonstrated the antioxidant activities of red cabbage (RC), and here, we aimed to determine the in vivo effects of 2-month long RC consumption using a high-fat/high-fructose model of diabetic rats. RESULTS: This vegetable, associated with lifestyle measurement, was shown to decrease OS and increase vascular endothelial NO synthase expression, ensuring vascular homeostasis. In the liver, RC consumption decreased OS by inhibiting p22phox expression and Nrf2 degradation and increasing catalase activity. It inhibited the activation of SREBP (1c, 2), ChREBP, NF-κB, ERK1/2, PPARγ, and GS and SIRT1 decrease, as observed in diabetic rats. CONCLUSION/INNOVATION: RC consumption led to metabolic profile improvement, together with hepatic function improvements. Although lifestyle changes are not sufficient to prevent diabetic complications, enrichment with RC avoids progression hepatic complications. This antioxidant strategy using RC does not only able to increase antioxidant defense, such as classical antioxidant, but also able to assure a metabolic and energetic balance to reverse complications. Whereas traditional medical therapy failed to reverse NASH in diabetic patients, consumption of RC should be a natural therapy to treat it.

Beneficial effects of cherry consumption as a dietary intervention for metabolic, hepatic and vascular complications in type 2 diabetic rats.

BACKGROUND: Oxidative stress (OS) plays an important role in type 2 diabetes (T2D) pathogenesis and its complications. New therapies target natural antioxidants as an alternative and/or supplemental strategy to prevent and control them. Our previous chemical and biological studies highlighted the important antioxidant activities of cherries, among other fruits and vegetables, thus we aimed to determine in vivo effects of 2-month long cherry consumption using a high-fat/high-fructose (HFHF) model of diabetic-rats (Lozano et al. in Nutr Metab 13:15, 2016). METHODS: After 2 months of HFHF, male Wistar rats were divided into: HFHF and HFHF enriched in cherry (nutritional approach) or standard diet ND (lifestyle measures) and ND plus cherry during 2 months. Metabolic, lipidic, oxidative parameters were quantified. Tissues (liver, pancreas and vessels) OS were assessed and hepatic (steatosis, fibrosis, inflammation) and vascular (endothelial dysfunction) complications were characterized. RESULTS: T2D was induced after 2 months of HFHF diet, characterized by systemic hyperglycaemia, hyperinsulinemia, glucose intolerance, dyslipidaemia, hyperleptinemia, and oxidative stress associated with endothelial dysfunction and hepatic complications. Cherry consumption for 2 months, in addition to lifestyle measures, in T2D-rats decreased and normalized the systemic disturbances, including oxidative stress complications. Moreover, in the vessel, cherry consumption decreased oxidative stress and increased endothelial nitric oxide (NO) synthase levels, thus increasing NO bioavailability, ensuring vascular homeostasis. In the liver, cherry consumption decreased oxidative stress by inhibiting NADPH oxidase subunit p22phox expression, nuclear factor erythroid-2 related factor 2 (Nrf2) degradation and the formation of reactive oxygen species. It inhibited the activation of sterol regulatory element-binding proteins (1c and 2) and carbohydrate-responsive element-binding protein, and thus decreased steatosis as observed in T2D rats. This led to the improvement of metabolic profiles, together with endothelial and hepatic function improvements. CONCLUSION: Cherry consumption normalized vascular function and controlled hepatic complications, thus reduced the risk of diabetic metabolic disorders. These results demonstrate that a nutritional intervention with a focus on OS could prevent and/or delay the onset of vascular and hepatic complications related to T2D.

High-fructose and high-fat diet-induced disorders in rats: impact on diabetes risk, hepatic and vascular complications.

BACKGROUND: As a result of the increased consumption of sugar-rich and fatty-products, and the increase in preference for such products, metabolic disorders are becoming more common at a younger age. Fructose is particularly used in prepared foods and carbonated beverages. We investigated the impact of regular consumption of fructose, in combination or not with fatty food, on the onset of metabolic syndrome and type 2 diabetes (T2D). We evaluated the metabolic, oxidative, and functional effects on the liver and blood vessels, both related to diabetes complications. METHODS: High-fat diet (HFD), high-fructose beverages (HF) or both (HFHF) were compared to rats fed with normal diet (ND) for 8 months to induce T2D and its metabolic, oxidative, and functional complications. Metabolic control was determined by measuring body weight, fasting blood glucose, C-peptide, HOMA2-IR, leptin, and cholesterol; oxidative parameters were studied by lipid peroxidation and total antioxidant capacity in plasma and the use of ROS labelling on tissue. Histological analysis was performed on the liver and endothelial function was performed in main mesenteric artery using organ-baths. RESULTS: After 2 months, HFHF and HFD increased body weight, leptin, HOMA2-IR associated to steatosis, oxidative stress in plasma and tissues, whereas HF had only a transient increase of leptin and c-peptide. Only HFHF induced fasting hyperglycaemia after 6 months and persistent hyperinsulinaemia and fasting hyperglycaemia with complicated steatosis (inflammation and fibrosis) after 8 months. HFHF and HFD induced endothelial dysfunction at 8 months of diet. CONCLUSIONS: Six months, high fat and high carbohydrate induced T2D with widespread tissues effects. We demonstrated the role of oxidative stress in pathogenesis as well as in complications (hepatic and vascular), reinforcing interest in the use of antioxidants in the prevention and treatment of metabolic diseases, including T2D.

HPLC-DAD-MS Profiling of Polyphenols Responsible for the Yellow-Orange Color in Apple Juices of Different French Cider Apple Varieties.

The pigments responsible for the yellow-orange coloration of apple juices have remained largely unknown up to now. Four French cider apple juices were produced in conditions similar to those used in the cider-making industry. The oxidized juices, characterized using the CIE L a b parameters, displayed various colors depending on the apple variety and native phenolic composition. HPLC-DAD-MS revealed contrasting pigment profiles related to oxidized tanning and nontanning molecules. The latter were divided into two groups according to their polarity and their visible spectra. With regard to phenolic classes, flavanol monomers and hydroxycinnamic acids played an essential role in the formation of oxidation products. Interestingly, dihydrochalcones appeared to include precursors of some yellow compounds. Indeed, the yellow pigment phloretin xyloglucoside oxidation product (PXGOPj), derived from phloretin xyloglucoside, was clearly identified in apple juices as a xyloglucose analogue of the yellow pigment phloridzin oxidation product (POPj), previously characterized in a model solution by Le Guernevé et al. (Tetrahedron Lett. 2004, 45 (35), 6673-6677).

In vitro uptake evaluation in Caco-2 cells and in vivo results in diabetic rats of insulin-loaded PLGA nanoparticles.

PLGA nanoparticles (NPs) are largely developed for biological applications but little is known about their uptake. Therefore, we focused our study on the modalities of insulin-loaded PLGA NPs transport across Caco-2 monolayers, and their hypoglycaemic effect on diabetic rats. Insulin-loaded PLGA NPs were formulated by a double emulsion solvent evaporation process. NPs mean diameter was between 130 and 180 nm. NPs were smooth and spherical with an entrapment efficiency above 80%. Fluorescently labeled NPs were incubated with Caco-2 cells to study the process of uptake and the intracellular fate by flow cytometry and confocal laser scanning microscopy. The kinetic of absorption was time-dependent and occurred by clathrin-mediated endocytosis. The intracellular traffic led to a basolateral exocytosis of NPs. In vitro studies and in vivo intraduodenal administration to diabetic rats showed that NPs were resistant in intestinal conditions long enough to allow both the intestinal absorption of NPs and the delivery of functional insulin in bloodstream. The resulting in vivo hypoglycaemic effect was similar to a long-acting insulin one. As no effect on glycaemia occurred after oral administration, further studies need to be conducted to protect NPs from the degradation occurring at the enteric level.