Neuroprotective And Therapeutic Effects Of Ginsenoside Rg1 On Parkinson's Disease Rats And Its Mechanism

Objectives To investigate the neuroprotective and therapeutic effects of ginsenoside Rg1 on the 6-OHDA-lesioned PD rat model and elucidate the underlying mechanisms.Methods 160 adult male SD rats were randomly divided into control group,model group,early-administration group and later-administration group.Unilateral infusion of 6-OHDA into the two points of striatum was conducted to lesion the nigrostriatal dopamine pathway.The striatum of the control group was injected with saline at the two points.In the early-administration group,ginsenoside Rg1(2mg/100g)was injected intraperitoneally 1 hour before the operation,and the same dose of Rg1 was administered daily for the next 6 weeks.In the later-administration group,administration was started 14 days after the modeling.Performed at 4 and 6 weeks after modeling,rat behavioral tests were carried out,including Rotarod test,pole test and suspension test;Immunohistochemical staining was conducted to detect nigrotyrosine hydroxylase(TH),and evaluate the damage degree of dopaminergic neurons;The content of dopamine and its metabolites in the striatum were determined by HPLC.The changes of the expression of EphA5 and EphB6 in the midbrain were detected by RT-PCR and Western-blot.Results 1 Four weeks after 6-OHDA lesions,the motor behavioral ability of rats in the model group,early-administration group and later-administration group decreased to different degrees.Compared with the model group,the motor behavioral ability of rats in the Rg1 administration group was significantly improved.Six weeks after the operation,the motor behavior of rats in the Rg1 group was further improved,while the model group showed no significant change.In addition,the improvement of motor behavior in the early-administration group was better than that in the later-administration group.2 Four weeks after the operation,the number of TH immunopositive neurons in the model group,early-administration group and later-administration group was significantly lower than the control group,of which the degree of dopaminergic neurons damage in the model group(91.00±1.63)%,early-administration group(64.59±10.52)% and later-administration group(78.59±3.99)% were statistically different(P<0.05).However,6 weeks after 6-OHDA infusion,no significant statistical difference was found in these groups when compared to the results of two weeks ago.3 Compared to the control group,the content of dopamine and its metabolites in the model group,early-administration group and later-administration group were significantly reduced four weeks after the operation.The model group had the lowest content,followed by the later-administration group,and the early-administration group was higher than that of the model group and the later-administration group.There was a statistically significant difference between the three groups(P<0.05).In addition,at 6 weeks after operation,the levels of dopamine and its metabolites in the early-administration group and the later-administration group were further increased compared to 4 weeks after the operation(P<0.05),while there was no significant change in the model group.4 Four weeks after modeling,the expression levels of EphA5 mRNA and protein in the model group were significantly lower than those in the control group(P<0.01).However,the expression levels of EphB6 mRNA and protein in the model group were not significantly different from those in the control group.Compared with the model group,the expression level of EphA5 mRNA and protein in the Rg1 administration group was significantly increased(P<0.01),while the expression level of EphB6 was not.At 6 weeks after operation,the expression levels of mRNA and protein of EphA5 in the Rg1 administration group were further increased compared to 4 weeks after the operation(P<0.05),while there was no significant change in the model group.Moreover,the expression level of EphA5 in the early-administration group was always higher than that in the later-administration group(P<0.05).Conclusions 1 Ginsenoside Rg1 has neuroprotective and therapeutic effects,which can significantly improve the motor behavior of 6-OHDA-induced PD rat model,reduce the degree of damage of dopaminergic neurons,increase the content of dopamine and its metabolites.2 Ginsenoside Rg1 may exert neuroprotective and therapeutic effects by up-regulating the expression of EphA5.Figure 11;Table 19;Reference 103.