Improvement Of Schisandrin A On The Learning And Memory Impairment Induced By D-galactose In Mice And The Underlying Mechanisms

Objective:To observe the improvement of Schisandrin A?SCA?on the Learning and memory impairment induced by D-galactose in mice and the underlyingmechanisms.Methods:?1?One hundred and fifty ICR mice were randomly divided into 5 groups:control group?distilled water orally,saline subcutaneously?,model group?distilled water orally,220 mg·kg-1 D-galactose subcutaneously?,and three SCA groups(1.25 mg·kg^-1,2.50 mg·kg^-11 and 5.00 mg·kg^-11 SCA orally,220 mg·kg-1 D-galactose subcutaneously).All treats were administered continuously for 42 days.?2?The step-through test and Morris water maze test were used to observe the effects of SCA on the learning and memory.?3?The activity of superoxide dismutase?SOD?,the level of malondialdehyde?MDA?in the peripheral blood and hippocampus of mice were detected by WST-1 and TBA methods.The content of 8 hydroxy deoxy guanosine?8-OHdG?in the hippocampus of mice were detected by immunosorbent assay.?4?Quantitative real-time PCR and Western Blot were respectively used to detect the expression of p19,p53,p21,cyclin D1,CDK4 and RB genes,and the phosphorylation of RB in the hippocampus of mice.Results:Behavioral tests showed that SCA significantly improved the learning and memory impairment of the model mice;increased the activity of SOD,decreased the content of MDA in both peripheral blood and hippocampus of the mice;decreased the content of 8-OHDG in the hippocampus of mice;reduced the expression of p19,p53 and p21 genes;elevated the expression level of cyclin D1and CDK4;and increased the phosphorylation of RB protein in the hippocampus.Conclusion:SCA can significantly improve the D-GAL induced learning and memory impairment,which may be related the increase of the antioxidant capacity through the elevation of SOD activity the decrease of MDA and 8-OHdG contend in mice;reduction of the expression of p19/p53/p21gene,elevated the expression level of cyclin D1 and CDK4 gene and the phosphorylation level of RB protein in mouse hippocampus and regulation of cell cycle.