Non-genomic effects of ginsenoside-Re in endothelial cells via glucocorticoid receptor

We demonstrated that ginsenoside-Re (Re), a pharmacological active component of ginseng, is a functional ligand of glucocorticoid receptor (GR) using competitive ligand-binding assay (IC50 = 156.6 nM; Kd = 49.7 nM) and reporter gene assay. Treatment with Re (1 μM) raises intracellular Ca2+ ([Ca2+]i) and nitric oxide (NO) levels in human umbilical vein endothelial cells as measured using fura-2 and 4-amino-5-methylamino-2′,7′-difluorofluorescein diacetate, respectively. Western blot analysis shows that Re increased phosphorylation of endothelial nitric oxide synthase. These effects were abolished by GR antagonist RU486, siRNA targeting GR, non-selective cation channel blocker 2-aminoethyldiphenylborate, or in the absence of extracellular Ca2+, indicating Re is indeed an agonistic ligand for the GR and the activated GR induces rapid Ca2+ influx and NO production in endothelial cells.