The Molecular Mechanism Of Notoginsenoside Rg1 Upregulating The Antioxidants And Resisting Oxidation And Aging In Rats

[Objective] To underlying investigate anti-ageing molecular mechanisms of the notoginsenoside Rgl, we combined Aβ_1-42 (amyloid beta peptide (Abeta) 1-42), with D-galactose to establish aging rat model.[Methods] Ninety rats were divided into three groups at random:sham group, model group, treatment group. Aging rats model were established by injecting peritoneally D-Galactose (100 mg/kg) to the rats for 56 days and after 35 days aggregated Aβ-(1-42) (μg) was injected to the right lateral ventricle of rats. Meantime, rats were treated by intragastric administration the notoginsenoside Rgl. Then experimental rats were examined spatial memory with the Morris water maze (MWM). The Hydrogen peroxide (H₂O₂), malondialdehyde (MDA), Nitric Oxide (NO), nitric oxide synthase (NOS) and antioxidants including glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD) activities were examined by colorimetric method in cerebral cortex and hippocampus. The concentration of the pro-caspase-3 and Bcl-2 were examined by the immunohistochemistry and Western blotting methods.[Results] The aging model rats exhibited significant an increase in escape latercies (P＜0.05), while a decrease in the time of staying the third quadrants of platform, the number of crossing over a platform as compared to sham group (P＜0.05). After treatment of the notoginsenoside Rgl, the aging model rats exhibited significant an increase in the time of staying the third quadrants of platform, the number of crossing over a platform (P<0.05), while a decrease in escape latercies as compared to control group (P＜0.05). The aging model rats exhibited significant an increase in the concentration of the H₂O₂, MDA, NO, NOS (P＜0.05), while a decrease in the concentration of the GSH, GR, GSH-Px, T-SOD and pro-caspase-3 as compared to sham group in cortex and hippocampus of the rats (P＜0.05). After treatment of the notoginsenoside Rg1, the aging model rats exhibited significant an increase in the concentration of the NO, NOS, GSH, GR, GSH-Px, T-SOD and pro-caspase-3 (P<0.05), while a decrease in H₂O₂, MDA as compared to control group in cortex and hippocampus of the rats (P＜0.05). Moreover there were not significant difference in the expression of the Bcl-2 among different groups (P>0.05)[Conclusions] The results from our study indicate that:(1) Aβ_1-42 combinated with D-galactose could impair the oriented learning and memory capacity and induce the neurodegeneration of central nervous systems in model rats by up-regulating the concentration of H₂O₂, MDA, down-regulating the antioxidants (including GSH, GR, GSH-Px, T-SOD) and increasing the cleavage of the pro-caspase-3. (2) The notoginsenoside Rgl could improve the oriented learning and memory capacity and prevent the neurodegeneration of central nervous systems in aging model rats by up-regulating the expression of the NO, NOS, the antioxidants (including GSH, GR, GSH-Px, T-SOD), down-regulating the concentration of the H₂O₂, MDA, and resisting the cleavage of the pro-caspase-3.