1. Academic Validation
  2. Protopanaxadiol and protopanaxatriol bind to glucocorticoid and oestrogen receptors in endothelial cells

Protopanaxadiol and protopanaxatriol bind to glucocorticoid and oestrogen receptors in endothelial cells

  • Br J Pharmacol. 2009 Feb;156(4):626-37. doi: 10.1111/j.1476-5381.2008.00066.x.
Kar Wah Leung 1 Fung Ping Leung Nai Ki Mak Joyce Tombran-Tink Yu Huang Ricky N S Wong
Affiliations

Affiliation

  • 1 Department of Biology, Hong Kong Baptist University, Hong Kong, China.
Abstract

Background and purpose: Ginsenosides are used widely for medicinal purposes, but the mechanisms of their action are still unclear, although there is some evidence that these effects are mediated by nuclear receptors. Here we examined whether two metabolites of ginsenoside, protopanaxadiol (g-PPD) and protopanaxatriol (g-PPT), could modulate endothelial cell functions through the Glucocorticoid Receptor (GR) and oestrogen receptor (ER). EXPERIMENT APPROACHES: The effects of g-PPD and g-PPT on intracellular calcium ion concentration ([CA(2+)](i)) and nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) were measured using Fura-2-acetoxymethyl ester, 4-amino-5-methylamino-2',7'-difluorofluorescein and Griess reagent. Effects on expression of GR and ER isoforms in HUVECs were determined using reverse transcriptase-/Real-Time PCR and immunocytochemistry. Phosphorylation of endothelial NO Synthase (eNOS) was assessed by Western blotting.

Results: Ginsenoside protopanaxadiol and g-PPT increased [CA(2+)](i), eNOS phosphorylation and NO production in HUVECs, which were inhibited by the GR antagonist, RU486, the ER antagonist, ICI 182,780 and siRNA targeting GR or ERbeta. The NO production was CA(2+)-dependent and the [CA(2+)](i) elevation in HUVECs resulted from both intracellular CA(2+) release and extracellular CA(2+) influx.

Conclusions and implications: Ginsenoside protopanaxadiol and g-PPT were functional ligands for both GR and ERbeta, through which these ginsenoside metabolites exerted rapid, non-genomic effects on endothelial cells.

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