Ginsenoside Rg-1 prevents elevated cytosolic Ca(2+) via store-operated Ca(2+) entry in high-glucose–stimulated vascular endothelial and smooth muscle cells

BACKGROUND: Ginsenoside Rg-1 (Rg-1), a triterpenoid saponin abundantly present in Panax ginseng, is a type of naturally occurring steroid with known anti-diabetic and anti-inflammatory effects. In this study, we sought to confirm the effects and mechanisms of action of Rg-1 on store-operated Ca(2+) entry (SOCE) in human vascular endothelial cell line (EA) and murine aortic vascular smooth muscle cell line (MOVAS) cells exposed to high glucose. METHODS: Cytosolic Ca(2+) concentrations in EA and MOVAS cells were measured by monitoring fluorescence of the ratiometric Ca(2+)-indicator, Fura-2 AM. RESULTS: High glucose significantly increased Ca(2+) influx by abnormally activating SOCE in EA and MOVAS cells. Notably, this high glucose-induced increase in SOCE was restored to normal levels in EA and MOVAS cells by Rg-1. Moreover, Rg-1 induced reductions in SOCE in cells exposed to high glucose were significantly inhibited by the plasma membrane Ca(2+) ATPase (PMCA) blocker lanthanum, the Na(+)/K(+)-ATPase blocker ouabain, or the Na(+)/Ca(2+) exchanger (NCX) blockers Ni(2+) and KB-R7943. These observations suggest that the mechanism of action of Rg-1 inhibition of SOCE involves PMCA and Na(+)/K(+)-ATPase, and an increase in Ca(2+) efflux via NCXs in both EA and MOVAS cells exposed to high glucose. CONCLUSIONS: These findings indicate that Rg-1 may protect vascular endothelial and smooth muscle cells from Ca(2+) increases following exposure to hyperglycemic conditions.