Ginsenoside Rg1 modulates COX-2 expression in the substantia nigra of mice with MPTP-induced Parkinson disease through the P38 signaling pathway / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the role of P38 signaling pathway in modulating the expression of cyclooxygenase-2 (COX-2) in the substantia nigra (SN) of mice with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson disease (PD), and explore the possible mechanism of the dopaminergic (DA) neuron death in PD and the effects of ginsenoside Rg1 on the P38 signaling pathway and DA neurons.</p><p><b>METHODS</b>C57BL6 mice were treated with MPTP to produce the subacute PD model, and the behavioral changes were observed. Immunohistochemistry and Western blotting for tyrosine hydroxylase (TH), COX-2, prostaglandin E2 (PGE2) and phosphorylated P38 (p-P38) were used to observe the changes of positive cell number in the midbrain after treatment with ginsenoside Rg1.</p><p><b>RESULTS</b>Compared with the control mice, the mice with PD presented with typical symptoms of PD. The number of p-P38-, COX-2-, and PGE2-positive cells significantly increased in the SN area 6 h after the 3rd injection of 30 mg/kg MPTP (P<0.01). The number of TH-positive neurons in the PD model group was substantially reduced by about 60% (P<0.01) in 24 h after the 5th injection of MPTP. In mice with ginsenoside Rg1 treatment, the number of p-P38-, COX-2-, and PGE2-positive cells was reduced obviously 6 h after the 3rd injection of MPTP as compared with that in the model group (P<0.01). The number of TH-positive neurons in the SN was decreased by only 30% (P<0.01 vs control group) 24h after the 5th injection of MPTP.</p><p><b>CONCLUSION</b>P38 signaling pathway may play an important role in modulating COX-2 expression in the SN in the early stage of MPTP-induced subacute PD, and ginsenoside Rg1 may act on the P38 signaling pathway to protect the DA neurons in PD.</p>