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.

Ginsenoside Rg1 can restore hematopoietic function by inhibiting Bax translocation-mediated mitochondrial apoptosis in aplastic anemia

“…Rg1 has been used treat anemia and bone marrow damage for many years. It can alleviate hematopoietic homeostasis defects 34 , delay hematopoietic stem/progenitor cell senescence by influencing the SIRT6/NF-κB signaling axis 35 , and protect against HSC aging by regulating the SIRT1-FOXO3 and SIRT3-SOD2 signaling pathways 36 or by regulating bone marrow stromal cells 37 to recover hematopoietic function. The anti-apoptosis, effects of Rg1 have been proven in several studies, with Rg1 being capable of protecting cardiomyocytes 38 and lung epithelial cells 39 .In addition, in hematology studie, Rg1 has been shown to inhibit mitochondrial dysfunction 40 and, delay senescence in BMNCs 37 .…”

“…The anti-apoptosis, effects of Rg1 have been proven in several studies, with Rg1 being capable of protecting cardiomyocytes 38 and lung epithelial cells 39 .In addition, in hematology studie, Rg1 has been shown to inhibit mitochondrial dysfunction 40 and, delay senescence in BMNCs 37 . Rg1 can also inhibit apoptosis by decreasing Bax level and restore an abnormal Bcl-2/Bax ratio to normal levels 36 , 41 , 42 . Therefore, we investigated whether Rg1 can mitigate AA by preventing mitochondrial apoptosis in hematopoietic cells.…”

SRT1720 Protects Against CSE-Induced Cellular Senescence via Accelerates of FOXO3-PINK1-mediated Mitophagy

“…Concomitantly, CSE induced fragmented mitochondria accumulated and slightly mitophagy activation [27,28]. Activation of Sirt1 mediated Foxo3 deacetylation, resulting in an increase of Pink1 in HBEC treated with CSE, restoration of HBEC autophagy and protection against HBEC apoptosis [29,30]. SIRT1 inhibitor lead to suppressed Sirt1-Foxo3 signaling and Pink1 mediated mitophagy may participate in CSE induced downregulation of HBEC autophagy and increased HBEC apoptosis [31].…”

Molecular Mechanisms of Anti-aging Traditional Chinese Medicine with “Homology of Medicine and Food”: Under the Influence of Oxidative Stress

“…Third, SIRT1 has also been shown to protect against cellular senescence by deacetylating the FOXO3 transcription factor. For example, Ginsenoside Rg1 (Tang et al 2020) significantly increased the mRNA and protein levels of SIRT1 and FOXO3 in Sca-1 + HSC/HPCs, and significantly decreased the percentage of Sca-1 + HSC/HPCs blocked in the G1 phase. Therefore, Ginsenoside Rg1 may play an anti-aging effect by regulating the SIRT1/FOXO3 signaling pathway.…”