Neuroprotective effects of Suhexiang Wan on the in vitro and in vivo models of Parkinson’s disease

OBJECTIVE:To examine the role of KSOP1009(a modified formulation of Suhexiang Wan essential oil)in an animal model of Parkinson's disease(PD)induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine(MPTP)injection.METHODS:Cell toxicity,apoptosis,and reactive oxygen species(ROS)levels were analyzed in the human neuroblastoma cell line SH-SY5 Y.After that,changes in animal behavior and tyrosine hydroxylase(TH)protein levels in the substantia nigra(SN)of MPTP-injected mice were examined.Three different doses of KSOP1009(30,100,and 300 mg/kg,n=8 for each group)were administered daily for 7 d before MPTP injection and 14 d after MPTP injection,totaling 21 d.RESULTS:MPP+,the active metabolite of MPTP,decreased the viability of SH-SY5 Y cells,whereas KSOP1009 alleviated MPP+-induced cytotoxicity.KSOP1009(10 and 50 mg/m L)reduced MPP+-induced ROS generation compared with the control group.Treatment with 1 m M MPP+increased the percentage of depolarized/live cells,whereas KSOP1009 intake at a dose of 10 mg/m L decreased the percentage of these cells.The mean latency to fall in the rotarod test was reduced in mice treated with MPTP compared with the control group.However,mice receiving three different doses of KSOP1009 performed better than MPTP-treated animals.MPTP-treated mice were more hesitant and took longer to traverse the balance beam than the control animals.In contrast,KSOP1009-treated mice performed significantly better than MPTPtreated mice.Furthermore,the KSOP1009-treated groups had a significantly higher number of TH-positive neurons in the lesioned SN and significantly higher expression of TH in the striatum than the MPTP-treated group.MPTP treatment strongly induced Jun-N-terminal kinase(JNK)activation,whereas KSOP1009 suppressed MPTP-induced JNK activation.In addition,KSOP1009 intake reversed the decrease in the phosphorylation levels of c AMP-response element-binding protein in the brain of MPTP-treated mice.KSOP1009 also restored the decrease in dopaminergic neurons and dopamine levels in the brain of MPTP-treated mice.CONCLUSION:KSOP1009 protected mice against MPTP-induced toxicity by decreasing ROS formation and restoring mitochondrial function.