Ginsenoside Rg1 protects against Sca‑1+ HSC/HPC cell aging by regulating the SIRT1‑FOXO3 and SIRT3‑SOD2 signaling pathways in a γ‑ray irradiation‑induced aging mice model

Abstract

Aging is characterized by a progressive deterioration in metabolic functions. The present study aimed to investigate the antagonistic effects of ginsenoside Rg1 (Rg1) on the γ‑ray irradiation‑induced aging of mixed hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). C57BL/6 mice were divided into a control group, a γ‑ray irradiation group that served as an aging mouse model, and an Rg1 group. The Rg1 group was treated with Rg1 at dosage of 20 mg/kg/day for 7 days prior to γ‑ray irradiation. The aging mouse model was established by exposing the mice to 6.5‑Gy γ‑ray total‑body irradiation. Stem cell antigen 1 positive (Sca‑1+) HSC/HPCs isolated from the mice were examined using a senescence‑associated β‑galactosidase (SA‑β‑Gal) staining assay. The cell cycle of the HSC/HPCs was examined using flow cytometry. A mixed hematopoietic progenitor cell colony‑forming unit (CFU‑mix) assay was also conducted. The mRNA and protein expression levels of sirtuin 1 (SIRT1), SIRT3, forkhead box O3 (FOXO3) and superoxide dismutase (SOD2) were evaluated using western blot and reverse transcription‑quantitative PCR assays. The results indicated that Rg1 treatment significantly increased white blood cell, red blood cell and platelet counts in peripheral blood compared with those in the γ‑ray irradiation group (P<0.05). However, Rg1 significantly attenuated the senescence of Sca‑1+ HSC/HPCs in the γ‑ray irradiation aging mice model. The proportion of SA‑β‑Gal stained HSC/HPCs was significantly decreased and CFU‑Mix counts were significantly increased in the Rg1 group compared with the γ‑ray irradiation group (P<0.05). Rg1 significantly increased the mRNA and protein levels of SIRT1, SIRT3, FOXO3 and SOD2 in the Sca‑1+ HSC/HPCs compared with those in the γ‑ray irradiation group (P<0.05). The percentage of Sca‑1+ HSC/HPCs arrested at the G1 phase in the Rg1 group was significantly decreased compared with that in the γ‑ray irradiation group (P<0.05). In conclusion, the present study indicates that Rg1 exerts anti‑aging effects via the regulation of SIRT1‑FOXO3 and SIRT3‑SOD2 signaling pathways, and triggering the progression of Sca‑1+ HSC/HPCs from the G1 phase to the S phase in γ‑ray irradiation‑induced aging mice.