Blockade of nitroxidative stress by roasted licorice extracts in high glucose-exposed endothelial cells.

Diabetes can cause a wide variety of vascular complications and endothelial dysfunction. In this study, human vascular endothelial cells were exposed to 5.5 mM and 33 mM glucose for 5 d in the absence and presence of 1 to 20 mug/mL roasted licorice (Glycyrrhiza inflata Bat.) ethanol extracts (rLE). Caspase-3 activation and Annexin V staining revealed that high glucose induced endothelial apoptotic toxicity with a generation of reactive oxygen species (ROS) and these effects were reversed by rLE at >/=1 mug/mL in a dose-dependent manner. Cytoprotective rLE substantially reduced high glucose-induced expression of endothelial nitric oxide synthase (eNOS), and hence attenuated the formation of peroxynitrite radicals derived from NO. In addition, rLE suppressed expression of PKCbeta2 and activation of NADPH oxidase subunit of p22phox promoted by high glucose. However, rLE </=1 mug/mL did not modulate the high glucose-triggered activation of ASK-JNK signaling pathway. Our results suggest that PKCbeta2 expression and NADPH oxidase-dependent superoxide production and eNOS-mediated peroxynitrite generation may be essential mechanisms responsible for increased oxidative stress and endothelial apoptosis in chronic hyperglycemic conditions. Thus, rLE may be a beneficial agent most likely contributing to prevention of vascular NADPH oxidase induction and preservation of endothelial nitric oxide availability, resulting in blunting diabetes-associated endothelial dysfunction and vascular complications.