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  • Title: Ginsenoside Rg1 enhances the resistance of hematopoietic stem/progenitor cells to radiation-induced aging in mice.
    Author: Chen C, Mu XY, Zhou Y, Shun K, Geng S, Liu J, Wang JW, Chen J, Li TY, Wang YP.
    Journal: Acta Pharmacol Sin; 2014 Jan; 35(1):143-50. PubMed ID: 24335839.
    Abstract:
    AIM: To investigate the effects of ginsenoside Rg1 on the radiation-induced aging of hematopoietic stem/progenitor cells (HSC/HPCs) in mice and the underlying mechanisms. METHODS: Male C57BL/6 mice were treated with ginsenoside Rg1 (20 mg·kg(-1)·d(-1), ip) or normal saline (NS) for 7 d, followed by exposure to 6.5 Gy X-ray total body irradiation. A sham-irradiated group was treated with NS but without irradiation. Sca-1(+) HSC/HPCs were isolated and purified from their bone marrow using MACS. DNA damage was detected on d 1. The changes of anti-oxidative activities, senescence-related markers senescence-associated β-galactosidase (SA-β-gal) and mixed colony-forming unit (CFU-mix), P16(INK4a) and P21(Cip1/Waf1) expression on d 7, and cell cycle were examined on d 1, d 3, and d 7. RESULTS: The irradiation caused dramatic reduction in the number of Sca-1(+) HSC/HPCs on d 1 and the number barely recovered until d 7 compared to the sham-irradiated group. The irradiation significantly decreased SOD activity, increased MDA contents and caused DNA damage in Sca-1(+) HSC/HPCs. Moreover, the irradiation significantly increased SA-β-gal staining, reduced CFU-mix forming, increased the expression of P16(INK4a) and P21(Cip1/Waf1) in the core positions of the cellular senescence signaling pathways and caused G1 phase arrest of Sca-1(+) HSC/HPCs. Administration of ginsenoside Rg1 caused small, but significant recovery in the number of Sca-1(+) HSC/HPCs on d 3 and d 7. Furthermore, ginsenoside Rg1 significantly attenuated all the irradiation-induced changes in Sca-1(+) HSC/HPCs, including oxidative stress reaction, DNA damage, senescence-related markers and cellular senescence signaling pathways and cell cycle, etc. CONCLUSION: Administration of ginsenoside Rg1 enhances the resistance of HSC/HPCs to ionizing radiation-induced senescence in mice by inhibiting the oxidative stress reaction, reducing DNA damage, and regulating the cell cycle.
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