Fatma Hadrich1, Marie Garcia2, Amina Maalej1, Marthe Moldes2, Hiroko Isoda3, Bruno Feve2, Sami Sayadi4. 1. Environmental Bioprocesses Laboratory, Laboratoire Mixte International (LMI-COSYS-MED), Sfax Biotechnology Center, P.O. Box 1177, Sfax 3038, Tunisia. 2. INSERM UMR S938, Centre de Recherche Saint-Antoine, F-75012 Paris, France. 3. Alliance for Research on North Africa (ARENA), University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan; Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan. 4. Environmental Bioprocesses Laboratory, Laboratoire Mixte International (LMI-COSYS-MED), Sfax Biotechnology Center, P.O. Box 1177, Sfax 3038, Tunisia.. Electronic address: sami.sayadi@cbs.rnrt.tn.
Abstract
AIMS: Oleuropein has been recognized as an important medicinal compound because of its various biological properties, including anti-cancer, antidiabetic and anti-atherosclerotic activities. Here, we evaluate the antioxidant activity as well as the mechanism of the hypoglycemic effects of oleuropein in C2C12 cells and we establish the mechanism underlying these effects. MAIN METHODS: To perform this study, C2C12 cells viability was analyzed via MTT assay and the antioxidant activity was investigated by ROS and TBARS assays. Also, the effect of oleuropein on AMPK and PI3 kinase signaling pathways was evaluated. KEY FINDINGS: Treatment with oleuropein was able to protect cells against H2O2 induced stress in cells. On the other hand, the molecular bases of its actions have been scarcely understood. Oleuropein significantly enhanced glucose consumption and the phosphorylation of AMPK (AMP-activated protein kinase/ACC (acetyl-CoA carboxylase)) and MAPKs (mitogen-activated protein kinases), but not PI3 kinase (Phosphatidylinositol 3-kinase)/Akt. However, the co-treatment of oleuropein and insulin improved the insulin sensitivity via insulin-dependent (PI3 kinase/Akt) and insulin independent (AMPK/ACC) pathways. These results could be confirmed from the findings of GLUT4 translocation which was strongly enhanced in the case of oleuropein. SIGNIFICANCE: Our results provide important insights for the possible mechanism of action of oleuropein as a therapeutic agent in diabetic patients.
AIMS: Oleuropein has been recognized as an important medicinal compound because of its various biological properties, including anti-cancer, antidiabetic and anti-atherosclerotic activities. Here, we evaluate the antioxidant activity as well as the mechanism of the hypoglycemic effects of oleuropein in C2C12 cells and we establish the mechanism underlying these effects. MAIN METHODS: To perform this study, C2C12 cells viability was analyzed via MTT assay and the antioxidant activity was investigated by ROS and TBARS assays. Also, the effect of oleuropein on AMPK and PI3 kinase signaling pathways was evaluated. KEY FINDINGS: Treatment with oleuropein was able to protect cells against H2O2 induced stress in cells. On the other hand, the molecular bases of its actions have been scarcely understood. Oleuropein significantly enhanced glucose consumption and the phosphorylation of AMPK (AMP-activated protein kinase/ACC (acetyl-CoA carboxylase)) and MAPKs (mitogen-activated protein kinases), but not PI3 kinase (Phosphatidylinositol 3-kinase)/Akt. However, the co-treatment of oleuropein and insulin improved the insulin sensitivity via insulin-dependent (PI3 kinase/Akt) and insulin independent (AMPK/ACC) pathways. These results could be confirmed from the findings of GLUT4 translocation which was strongly enhanced in the case of oleuropein. SIGNIFICANCE: Our results provide important insights for the possible mechanism of action of oleuropein as a therapeutic agent in diabeticpatients.