Laboratory of Stem Cells and Tissue Engineering, Department of Histology and Embryology, Chongqing Medical University, Chongqing, 400016, China.
Department of Cardiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China; Institute of Life Science, Chongqing Medical University, Chongqing, 400016, China.
Free Radic Biol Med. 2021 Oct;174:182-194. doi: 10.1016/j.freeradbiomed.2021.08.007. Epub 2021 Aug 6.
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.
衰老限制了间充质干细胞(MSCs)的特性和功能,从而严重限制了它们在组织工程中的应用。在这里,我们研究了防止 MSCs 进入衰老状态的方法。我们发现,人参提取物 Rg1 可以降低体外培养细胞和体内各种组织中衰老标志物的表达。同时,人参皂苷 Rg1 提高了细胞的抗氧化能力,Rg1 的抗衰老和抗氧化作用与核因子 E2 相关因子 2(NRF2)信号通路的激活有关。此外,Rg1 可能通过上调 P62 和激活 AKT 来增加 P62 与 KEAP1 的相互作用,从而激活 NRF2 通路。总之,我们的研究结果表明,Rg1 通过 NRF2 和 AKT 防止细胞衰老,激活 AKT 或 NRF2 可能成为预防细胞衰老的治疗靶点。