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 (IC(50)=156.6 nM; K(d)=49.7 nM) and reporter gene assay. Treatment with Re (1 microM) raises intracellular Ca(2+) ([Ca(2+)](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 Ca(2+), indicating Re is indeed an agonistic ligand for the GR and the activated GR induces rapid Ca(2+) influx and NO production in endothelial cells.
Leung
Kar Wah
KW
Department of Biology, Hong Kong Baptist University, Hong Kong. kwl_melody@yahoo.co.uk
Leung
Fung Ping
FP
Huang
Yu
Y
Mak
Nai Ki
NK
Wong
Ricky N S
RN
D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D036145:Ginsenosides / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009569:Nitric Oxide / Q000096:biosynthesis; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000502:physiology*; D014471:Umbilical Veins
D036145:Ginsenosides; D011965:Receptors, Glucocorticoid; D009569:Nitric Oxide; C049864:ginsenoside Re; C035054:ginsenoside Rg1; D002118:Calcium