Activating glucocorticoid receptor-ERK signaling pathway contributes. to ginsenoside Rg1 protection against β-amyloid peptide-induced human endothelial cells apoptosis

The deposition of beta-amyloid (A beta) in neurons and vascular cells of the brain has been characterized in Alzheimer's disease. Ginsenoside Rg1 (Rg1) is an active components in Panax ginseng, a famous traditional Chinese medicines recorded in Compendium of Materia Medica. Present study attempted to evaluate the potential mechanisms of A beta-mediated insult and the protective effects of Rg1 on human endothelial cells. Rg1 attenuated the A beta(25-35)-associated mitochondrial apoptotic events, accompanied by inhibiting HIF-1 alpha expression followed by intracellular reactive nitrogen species generation, and protein nitrotyrosination. These protective effects were abolished by glucocorticoid receptor (GR) antagonist RU486 or p-ERK inhibitor U0126 rather than estrogen receptor alpha antagonist ICI 82,780. Taken together, our results suggested that Rg1 protected against A beta(25-35)-induced apoptosis at least in part by two complementary GR-dependent ERR phosphorylation pathways: (1) down-regulating HIF-1 alpha initiated protein nitrotyrosination, and (2) inhibiting mitochondrial apoptotic cascades. These data provided a novel insight to the mechanisms of Rg1 protective effects on A beta(25-35)-induced endothelial cells apoptosis, suggesting that GR-ERK signaling pathway might play an important role in it. (C) 2013 Elsevier Ireland Ltd. All rights reserved.