Rg3 and Rh2 ginsenosides suppress embryoid body formation by inhibiting the epithelial-mesenchymal transition

Numerous active compounds derived from ginseng exhibit various pharmacological and therapeutic effects in humans. Despite the benefits of ginsenosides, little is known about their influence on embryonic development, especially in human embryonic models. In this study, we evaluated the effect of two ginsenosides (Rg3 and Rh2) on human embryonic development, using embryoid bodies and three-dimensional (3D) aggregates of pluripotent stem cells. We exposed embryoid bodies to varying concentrations of Rg3 and Rh2 (5, 10, and 25 μg/mL), and their embryotoxicity was evaluated by measuring the size of the embryoid body and the expression of epithelial-mesenchymal transition (EMT) markers. The growth rates of embryoid bodies were reduced upon treatment with a high concentration (25 μg/mL) of Rg3 and Rh2. In addition, Rg3 induced E-cadherin expression while inhibiting N-cadherin and vimentin expression, which implies the inhibition of EMT. Such a change in E-cadherin expression was not observed after Rh2 treatment, but the inhibition of N-cadherin and vimentin expression was observed to be consistent with that observed on treatment with Rg3. Taken together, using the human embryoid model, we found that the two active ginsenosides, Rg3 and Rh2, induce aberrant embryoid body formation and ablate normal EMT.