Ginsenoside Rg3 inhibits endothelial progenitor cell differentiation through attenuation of VEGF-dependent Akt/eNOS signaling.

Endothelial progenitor cells (EPCs) play a critical role both in vascular repair after cell transplantation for ischemic diseases and in the growth of early tumors by intervening with the angiogenic switch during tumor progression. This paper reports on the effect of ginsenoside Rg3 in EPCs as a candidate angiogenesis inhibitor for in vitro functional assays. CD34⁺ cells were isolated from human cord blood and the study investigated whether or not ginsenoside Rg3 regulated EPC bioactivities including cell proliferation, differentiation, migration and tube formation. Although ginsenoside Rg3 did not affect the ex vivo expansion of CD34 and/or KDR (VEGFR2) stem/progenitor cells, treatment with ginsenoside Rg3 led to a significant decrease in CD34-expressing cells, specifically the absolute number of expanded CD34⁺ cells. Importantly, a significantly decreased number of EPC colony-forming units among human cord blood-derived CD34⁺ cells was observed, implying that ginsenoside Rg3 inhibited EPC differentiation, in particular, the commitment to primitive EPC colonies (the early stage of EPC differentiation). Moreover, treatment of CD34-derived EPCs with ginsenoside Rg3 resulted in the attenuation of VEGF-dependent Akt/eNOS signaling as well as the inhibition of migration and tube formation. In conclusion, this study provides in vitro evidence for ginsenoside Rg3 as a potential therapeutic molecule, specifically as an angiogenesis inhibitor that functions by attenuating EPC bioactivities.