title: Ginsenoside-Rg1 induces angiogenesis via non-genomic crosstalk of glucocorticoid receptor and fibroblast growth factor receptor-1.
abstract: OBJECTIVE
  Ginsenoside-Rg1, the most prevalent active constituent of Panax ginseng, has been shown to possess potent pro-angiogenic properties and therefore poses special interest for the development as a novel modality for angiotherapy. Rg1 can activate the glucocorticoid receptor (GR). However, the mechanism that transmits these pro-angiogenic effects is still unclear.
  
  
  RESULTS
  By using human umbilical vein endothelial cells (HUVECs), we show for the first time that in the presence of Rg1, GR and fibroblast growth factor receptor-1 (FGFR-1) cooperate to activate a non-genomic signalling cascade that results in angiogenic activity. The activation of FGFR-1 by Rg1 was blocked by the GR antagonist RU486. Depletion of FGFR-1 expression or inhibition of its activity using small interfering RNA and small molecule inhibitor, respectively, significantly inhibited Rg1-induced phosphatidylinositol 3-kinase/Akt phosphorylation and subsequent endothelial nitric oxide synthase activation and angiogenic tube formation, confirming that the effect was FGFR-1 specific. On exploring how GR might regulate the activation of FGFR-1, we found that GR-mediated FGFR-1 activation was ligand-independent. In addition, we have shown that FGFR-1 regulation by GR was associated with GR/FGFR-1 complex formation.
  
  
  CONCLUSIONS
  This study provides important new insights into the mechanism regarding the beneficial effects of Rg1 on angiogenesis. We propose that Rg1 could be a novel prototype of nutraceutical that can induce therapeutic angiogenesis.
authors.affiliation: School of Biological Sciences, University of Hong Kong, 4S-14 Kadoorie Biological Sciences Building, Pokfulam Road, Hong Kong.
authors.forename: Lydia W T
authors.initials: LW
authors.lastname: Cheung
authors.forename: Kar Wah
authors.initials: KW
authors.lastname: Leung
authors.forename: Chris K C
authors.initials: CK
authors.lastname: Wong
authors.forename: Ricky N S
authors.initials: RN
authors.lastname: Wong
authors.forename: Alice S T
authors.initials: AS
authors.lastname: Wong
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation; D036145:Ginsenosides / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D015735:Mifepristone / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology; D034622:RNA Interference; D020239:Receptor Cross-Talk / Q000187:drug effects*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D036145:Ginsenosides; D006727:Hormone Antagonists; C497713:NR3C1 protein, human; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D011965:Receptors, Glucocorticoid; C105686:SU 5402; D015735:Mifepristone; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D058539:Phosphatidylinositol 3-Kinase; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051057:Proto-Oncogene Proteins c-akt; C035054:ginsenoside Rg1