Ginsenoside Rg1 enhances the resistance of hematopoietic stem/progenitor cells to radiation-induced aging in mice
Acta Pharmacologica Sinica(2013)
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 G 1 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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Key words
ginsenoside Rg1,hematopoietic stem and progenitor cell (HSC/HPC),ionizing radiation,cellular senescence,oxidative stress,DNA damage,cell cycle
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