Objective To investigate the effect and mechanism of salidroside on1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) in mice.
Methods C57BL/6J mice were induced by MPTP to establish a PD mouse model and the movement track of mice was recorded by open field experiment. The expression of tyrosine hydroxylase (TH), α-synuclein (α-syn), nuclear factor E2 associated factor 2 (Nrf2) and quinone oxidoreductase 1 (NQO1) were detected by immunohistochemistry in brain tissue of mice. SN4741 cells were stimulated by MPTP to establish a PD cell model in vitro. MPTP stimulation of SN4741 cells to establish an in vitro cell model of PD. After pretreatment with salidroside, TUNEL was used to detect cell apoptosis in each group. The expressions of TH, α-syn, Nrf2 and NQO1 were detected by immunofluorescence. Nrf2 expression was knocked down by being transfected with si-RNA, and apoptosis condition was detected by TUNEL assay. The expression levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) protein in brain tissue extract and cell culture were detected by enzyme-linked immunosorbent assay (ELISA).
Results The open field experiment results showed that salidroside could improve 3 min total distance of activity, average speed and activity track of PD mice (P < 0.05). Compared with the PD model mice, the salidroside treated mice showed significantly increased expression of TH, Nrf2 and NQO1 in the brain, and reduced expression of IL-18, α-Syn, IL-1β. Compared with the MPTP stimulated cells, the salidroside pretreatment group showed a decrease in cell apoptosis and an increase in the expressions of TH, Nrf2 and NQO1, but reduced expressions in α-Syn, IL-1β and IL-18. After si-RNA knockdown of Nrf2 expression, the protective effect of salidroside on MPTP stimulated cells weakened or even disappeared.
Conclusion Salidroside may alleviate neuronal apoptosis by activating Nrf2-ARE signaling pathway, which is expected to be a new drug for PD treatment.
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