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.
Choi
Yean-Jung
YJ
Department of Food and Nutrition and Korean Institute of Nutrition, BK 21, Hallym University, Chuncheon, Korea.
Lim
Soon Sung
SS
Jung
Ju-Young
JY
Choi
Jung-Suk
JS
Kim
Jin-Kyung
JK
Han
Seoung Jun
SJ
Kang
Young-Hee
YH
D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005021:Ethylamines / Q000378:metabolism; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D005452:Fluoresceins / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006035:Glycyrrhiza / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology
C527813:3-amino-4-monomethylamino-2',7'-difluorofluorecein; D005021:Ethylamines; D005452:Fluoresceins; D005456:Fluorescent Dyes; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D052250:Nitric Oxide Synthase Type III; D016650:Fluorescein-5-isothiocyanate; D005947:Glucose