Laboratory of Stem Cells and Tissue Engineering, Chongqing Medical University, Chongqing, China.
Department of Histology and Embryology, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
Neurochem Res. 2018 Feb;43(2):430-440. doi: 10.1007/s11064-017-2438-y. Epub 2017 Nov 17.
Adult hippocampal neurogenesis plays a pivotal role in learning and memory. The suppression of hippocampal neurogenesis induced by an increase of oxidative stress is closely related to cognitive impairment. Neural stem cells which persist in the adult vertebrate brain keep up the production of neurons over the lifespan. The balance between pro-oxidants and anti-oxidants is important for function and surviving of neural stem cells. Ginsenoside Rg1 is one of the most active components of Panax ginseng, and many studies suggest that ginsenosides have antioxidant properties. This research explored the effects and underlying mechanisms of ginsenoside Rg1 on protecting neural stem cells (NSCs) from oxidative stress. The sub-acute ageing of C57BL/6 mice was induced by subcutaneous injection of D-gal (120 mg kg day) for 42 day. On the 14th day of D-gal injection, the mice were treated with ginsenoside Rg1 (20 mg kg day, intraperitoneally) or normal saline for 28 days. The study monitored the effects of Rg1 on proliferation, senescence-associated and oxidative stress biomarkers, and Akt/mTOR signalling pathway in NSCs. Compared with the D-gal group, Rg1 improved cognitive impairment induced by D-galactose in mice by attenuating senescence of neural stem cells. Rg1 also decreased the level of oxidative stress, with increased the activity of superoxide dismutase and glutathione peroxidase in vivo and in vitro. Rg1 furthermore reduced the phosphorylation levels of protein kinase B (Akt) and the mechanistic target of rapamycin (mTOR) and down-regulated the levels of downstream p53, p16, p21 and Rb in D-gal treated NSCs. The results suggested that the protective effect of ginsenoside Rg1 on attenuating cognitive impairment in mice and senescence of NSCs induced by D-gal might be related to the reduction of oxidative stress and the down-regulation of Akt/mTOR signaling pathway.
成人海马神经发生在学习和记忆中起着关键作用。氧化应激增加引起的海马神经发生抑制与认知障碍密切相关。在成年脊椎动物大脑中持续存在的神经干细胞在整个生命周期内维持神经元的产生。促氧化剂和抗氧化剂之间的平衡对于神经干细胞的功能和存活很重要。人参皂苷 Rg1 是人参中最活跃的成分之一，许多研究表明人参皂苷具有抗氧化特性。本研究探讨了人参皂苷 Rg1 对保护神经干细胞（NSCs）免受氧化应激的作用及其潜在机制。通过皮下注射 D-半乳糖（120mg/kg/天）诱导 C57BL/6 小鼠亚急性衰老，共 42 天。在 D-半乳糖注射的第 14 天，用人参皂苷 Rg1（20mg/kg/天，腹腔注射）或生理盐水处理 28 天。该研究监测了 Rg1 对 NSCs 增殖、衰老相关和氧化应激生物标志物以及 Akt/mTOR 信号通路的影响。与 D-半乳糖组相比，Rg1 通过减轻神经干细胞衰老改善了 D-半乳糖诱导的小鼠认知障碍。Rg1 还降低了氧化应激水平，体内和体外超氧化物歧化酶和谷胱甘肽过氧化物酶的活性增加。Rg1 还降低了蛋白激酶 B（Akt）和雷帕霉素的机制靶点（mTOR）的磷酸化水平，并下调了 D-半乳糖处理的 NSCs 中下游 p53、p16、p21 和 Rb 的水平。结果表明，人参皂苷 Rg1 对减轻 D-半乳糖诱导的小鼠认知障碍和 NSCs 衰老的保护作用可能与降低氧化应激和下调 Akt/mTOR 信号通路有关。
