Ginsenoside Rg1 prevents bone marrow mesenchymal stem cell senescence via NRF2 and PI3K/Akt signaling.

Senescence limits the characteristics and functionality of mesenchymal stem cells (MSCs), thereby severely restricting their application in tissue engineering. Here, we investigated ways to prevent MSCs from entering a state of senescence. We found that Rg1, an extract of natural ginseng, can reduce the expression of senescence markers in cultured cells in vitro and in various tissues in vivo. Simultaneously, ginsenoside Rg1 improved the antioxidant capacity of cells, and the senescence-inhibiting and antioxidant effect of Rg1 were associated with the activation of the nuclear factor E2-related factor 2 (NRF2) signaling pathway. Furthermore, Rg1 may activate the NRF2 pathway by increasing the interaction between P62 and KEAP1through P62 upregulation and AKT activation. Taken together, our findings indicate that Rg1 prevents cell senescence via NRF2 and AKT, and activation of AKT or NRF2 may thus represent therapeutic targets for preventing cell senescence.