Ginsenoside Rg-1 prevents elevated cytosolic Ca²⁺ via store-operated Ca²⁺ 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 Ca²⁺ 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 Ca²⁺ concentrations in EA and MOVAS cells were measured by monitoring fluorescence of the ratiometric Ca²⁺-indicator, Fura-2 AM. Results: High glucose significantly increased Ca²⁺ 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 Ca²⁺ ATPase (PMCA) blocker lanthanum, the Na⁺/K⁺-ATPase blocker ouabain, or the Na⁺/Ca²⁺ exchanger (NCX) blockers Ni²⁺ 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 Ca²⁺ 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 Ca²⁺ increases following exposure to hyperglycemic conditions.