Effect of ginsenoside Rg1 on delaying radiation-induced senescence of hematopoietic stem cell and progenitor cell based on SIRT6/NF-κB signal pathway / 中草药

ABSTRACT

Objective To investigate the effect of SIRT6/NF-κB signal axis on delaying radiation-induced senescence of hematopoietic stem cell and progenitor cell with ginsenoside Rg1. Methods C57BL/6 mice were randomly divided into control group, model group and ginsenoside Rg1 group. The mice in model and ginsenoside Rg1 groups were exposed to total body irradiation with 6.5 Gy 60Coγ, the mice in ginsenoside Rg1 group were intraperitoneal injected with ginsenoside Rg1 (20 mg/kg) for 7 d before and after radiation. On day after taking medicine, the indicators in peripheral blood were observed to definite the information of hematopoietic reconstruction and the effect of ginsenoside Rg1 on it. Sca-1+ HSCs/HPCs were isolated and purified by magnetic activated cell sorting (MACS). The effect of ginsenoside Rg1 on delaying radiation-induced senescence of hematopoietic stem cell and progenitor cell was evaluated by mixed hematopoietic progenitor cell culture, cell cycle assay and senescence-associated β-galactosidase (SA-β-gal) staining. The expression of senescence associated SIRT6 and NF-κB mRNA and protein was examined by realtime fluorescence quantitative PCR (qRT-PCR) and Western blotting. Results After radiation, the indicator in peripheral blood of model group was decreased compared with control group. Sca-1+ HSC/HPC appeared aging character The number of cells entered G0/G1 phase, the percentage of SA-β-gal positive cells was increased, the expressing of SIRT6 mRNA and protein were down regulated and NF-κB mRNA and protein were up regulated, and the number of CFU-Mix was decreased. Compared with the model group, the number of white blood cells (RBC), red blood cells (RBC), and platelet (PLT) in mice were increased, the number of cells entered G0/G1 phase and the percentage of SA-β-gal positive cells were decreased, and the number of CFU-Mix was increased in Sca-1+ HSC/HPC from the ginsenoside Rg1 group. Moreover, the expression of SIRT6 mRNA and protein were up regulated, and NF-κB mRNA and protein were down regulated in the ginsenoside Rg1 group. Conclusion SIRT6/NF-κB signal axis may play a key role in the antiaging effect of ginsenoside Rg1 to Sca-1+ HSC/HPC senescence induced by radiation.