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Chen C.,Chongqing Medical University | Mu X.-Y.,Chongqing Medical University | Zhou Y.,Dali University | Shun K.,Chongqing Medical University | And 6 more authors.
Acta Pharmacologica Sinica

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), P16INK4a 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. © 2013 CPS. Source

Zhu J.,Chongqing Medical University | Mu X.,Chongqing Medical University | Zeng J.,Land Force Lintong Sanatorium | Xu C.,Chongqing Medical University | And 6 more authors.

Neurogenesis continues throughout the lifetime in the hippocampus, while the rate declines with brain aging. It has been hypothesized that reduced neurogenesis: may contribute to age-related cognitive impairment. Ginsenoside Rg1 is an active ingredient of Panax ginseng in traditional Chinese medicine, which exerts anti-oxidative and anti-aging effects. This study explores the neuroprotective effect of ginsenoside Rg1 on the hippocampus of the D-gal (D-galactose) induced aging rat model. Sub-acute aging was induced in male SD rats by subcutaneous injection of D-gal (120 mg/kg·d) for 42 days, and the rats were treated with ginsenoside Rg1 (20 mg/kg·d, intraperitoneally) or normal saline for 28 days after 14 days of D-gal injection. In another group, normal male SD rats were treated with ginsenoside Rg1 alone (20 mg/kg·d, intraperitoneally) for 28 days. It showed that administration of ginsenoside Rg1 significantly attenuated all the D-gal-induced changes in the hippocampus, including cognitive capacity, senescence-related markers and hippocampal neurogenesis, compared with the D-gal-treated rats. Further investigation showed that ginsenoside Rg1 protected NSCs/NPCs (neural stem cells/progenitor cells) shown by increased level of SOX-2 expression; reduced astrocytes activation shown by decrease level of Aeg-1 expression; increased the hippocampal cell proliferation; enhanced the activity of the antioxidant enzymes GSH-Px (glutathione peroxidase) and SOD (Superoxide Dismutase); decreased the levels of IL-1β, IL-6 and TNF-α, which are the proinflammatory cytokines; increased the telomere lengths and telomerase activity; and down-regulated the mRNA expression of cellular senescence associated genes p53, p21Cip1/Waf1 and p19Arf in the hippocampus of aged rats. Our data provides evidence that ginsenoside Rg1 can improve cognitive ability, protect NSCs/NPCs and promote neurogenesis by enhancing the antioxidant and anti-inflammatory capacity in the hippocampus. © 2014 Zhu et al. Source

Qu X.,Chongqing Medical University | Qu X.,Key Laboratory of Pediatrics in Chongqing | Qu X.,Cooperation Technology | Cao Y.,Chongqing Medical University | And 14 more authors.
Journal of Biomedical Materials Research - Part A

We explored a novel biodegradable poly(lactide-co-glycolide) (PLGA) film loaded with over 80 wt % bone morphogenetic protein (BMP)-2, which was regarded as a substrate-promoting osteoblast attachment, proliferation, and differentiation for application of bone tissue engineering. Using phospholipid as a surfactant, BMP-2 was modified as a complex (PBC) for dispersing in PLGA/dichloromethane solution. The PLGA film loaded with BMP-2 and phospholipid complex (PBC-PF) showed rough and draped morphology with high entrapment efficiency exceeding 80% and good hydrophilicity, respectively. The in vitro release study of BMP-2 showed that about 50% BMP-2 was slowly and continuously released from PBC-PF within 5 weeks and had a short initial burst release only in the last 1.5 days, which was better than serious burst release of PLGA film loaded with pure BMP-2 without phospholipid (BMP-PF) as control. By comparison with other PLGA films and tissue culture plates, it was confirmed that PBC-PF significantly promoted the attachment, proliferation, and differentiation of osteoblasts with higher entrapment efficiency and better sustained release. These advantages illustrated that PBC-PF could be a potential substrate providing long-term requisite growth factors for osteoblasts, which might be applied in bone tissue engineering. © 2015 Wiley Periodicals, Inc. Source

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