Aim of study:Parkinsons disease (PD) is the second most common chronic neurodegenerative disorder,after Alzheimers disease.Its pathological feature is damage to the nigrostriatal dopaminergic pathway.Until now,there has been no medicine for protecting dopamine neurons and retarding the development of PD.Old drug Levodopa (L-DOPA) is still the most effective drug for the treatment of PD.However,chronic exposure to the drug results to dyskinesia,and the effective period of L-DOPA treatment is only about three to five years.Ginseng saponins have been shown to have broad bioactive and pharmacological activities in the central nervous system.The aim of this study is to investigate whether a combination of ginseng Rb fraction (Rb) and L-DOPA has effects on protection of dopamine neurons and reduction of side effects caused by L-DOPA.Material and methods:(1) Rat PD model induced by rotenone was used to comparatively study the effects of Rb,L-DOPA and their combination on protection of dopamine neurons in the nigrostriatal dopaminergic pathway and the possible action mechanism;(2) Rat PD model induced by 6-hydroxydopamine (6-OHDA) was applied to investigate the effects of Rb against dyskinesia induced by L-DOPA and its active mechanism.Results:(1) In the rotenone induced PD model,the weight of rats was gradually reduced and their spontaneous activity and exploratory behavior were also reduced with a serious of abnormalities of motor behavior.There were large areas of damage of dopamine neural terminal in the striatum,but only few loss of dopamine neural cell body in the substantia nigra pars compacta,suggesting that the damage of dopamine neural terminal could precede that of dopamine neural cell body.These pathological changes were consistent with that in PD patients.Furthermore,damaged astrocytes,activated microglia and disrupted blood brain barrier were also observed in the striatum.Rb significantly prevented motor behavior impairment and microglia activation,protected dopamine neurons in the substantia nigra and its terminals in the striatum,and also protected astrocytes.L-DOPA was also some protective.Interestingly,these effects were significantly enhanced when a combination of Rb and L-DOPA was administrated.(2) In the 6-OHDA-induced PD model,a combination of Rb and L-DOPA also showed to have effects on the treatment of PD and maintain the effects after drug withdrawal.Furthermore,Rb remarkably reduced the dyskinesia induced by L-DOPA.Conclusions:Rb,especially,a combination of Rb and L-DOPA,significantly prevented the occurrence of PD,and effectively treated PD and reduced dyskinesia caused by L-DOPA.The possible action mechanisms are related to the protection of dopamine neurons and astrocytes,the prevention of microglial activation,and the mantainence of blood integrity.The results suggest that the combination of Rb and L-DOPA has a potential for the treatment of PD.