title: Cocoa flavonoids protect hepatic cells against high-glucose-induced oxidative stress: relevance of MAPKs.
abstract: METHODS
  Oxidative stress plays a main role in the pathogenesis of type 2 diabetes mellitus. Cocoa and (-)-epicatechin (EC), a main cocoa flavanol, have been suggested to exert beneficial effects in type 2 diabetes mellitus because of their protective effects against oxidative stress and insulin-like properties. In this study, the protective effect of EC and a cocoa phenolic extract (CPE) against oxidative stress induced by a high-glucose challenge, which causes insulin resistance, was investigated on hepatic HepG2 cells.
  
  
  RESULTS
  Oxidative status, phosphorylated mitogen-activated protein kinases (MAPKs), nuclear factor E2 related factor 2 (Nrf2) and p-(Ser)-IRS-1 expression, and glucose uptake were evaluated. EC and CPE regulated antioxidant enzymes and activated extracellular-regulated kinase and Nrf2. EC and CPE pre-treatment prevented high-glucose-induced antioxidant defences and p-MAPKs, and maintained Nrf2 stimulation. The presence of selective MAPK inhibitors induced changes in redox status, glucose uptake, p-(Ser)- and total IRS-1 levels that were observed in CPE-mediated protection.
  
  
  CONCLUSIONS
  EC and CPE recovered redox status of insulin-resistant HepG2 cells, suggesting that the functionality in EC- and CPE-treated cells was protected against high-glucose-induced oxidative insult. CPE beneficial effects on redox balance and insulin resistance were mediated by targeting MAPKs.
authors.affiliation: Department of Metabolism and Nutrition, Institute of Food Science and Technology and Nutrition (ICTAN), Consejo Superior de Investigaciones Científicas (CSIC), Ciudad Universitaria, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Cordero-Herrera
authors.forename: María Angeles
authors.initials: MA
authors.lastname: Martín
authors.forename: Luis
authors.initials: L
authors.lastname: Goya
authors.forename: Sonia
authors.initials: S
authors.lastname: Ramos
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002099:Cacao / Q000737:chemistry*; D002392:Catechin / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005419:Flavonoids / Q000494:pharmacology*; D005947:Glucose / Q000009:adverse effects*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D005980:Glutathione Reductase / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D005419:Flavonoids; D007004:Hypoglycemic Agents; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010636:Phenols; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D002392:Catechin; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D020928:Mitogen-Activated Protein Kinases; D005978:Glutathione; D005947:Glucose
keywords: Antioxidant defences; Cocoa flavanols; HepG2 cells; Insulin resistance; Oxidative markers