Salidroside Protection Against Oxidative Stress Injury Through the Wnt/β-Catenin Signaling Pathway in Rats with Parkinson's Disease

Background/Aims: Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease, and recent studies suggested that oxidative stress (OS) contributes to the cascade that leads to dopamine cell degeneration in PD. In this study, we hypothesized that salidroside (SDS) offers protection against OS injury in 6-hydroxydopamine (6-OHDA) unilaterally lesioned rats as well as the underlying mechanism. Methods:SDS and LiCI (activators of the Wnt/beta-catenin signaling pathway) administration alone and in combination with 6-OHDA injection in rats was performed 3 days before modeling for 17 consecutive days to verify the regulatory mechanism by which SDS affects the Wnt/beta-catenin signaling pathway as well as to evaluate the protective effect of SDS on PD in relation to OS in vivo. In addition, pheochromocytoma 12 (PC12) cells were incubated with 10 mu mol/L SOS or LiCI alone or with both in combination for 1 h followed by a 24-h incubation with 100 mu mol/L 6-OHDA to obtain in vitro data. Results: In vivo the administration of LiCI was found to ameliorate behavioral deficits and dopaminergic neuron loss; increase superoxide dismutase (SOA) activity, glutathione peroxidase (GSH-Px) levels, and glycogen synthase kinase 3 beta phosphorylation (GSK-3 beta-Ser9); reduce malondialdehyde (MDA) accumulation in the striatum and the GSK-3 beta mRNA level; as well as elevate p-catenin and cyclinD1 mRNA and protein levels in 6-OHDA-injected rats. This SDS treatment regimen was found to strengthen the beneficial effect of LiCI on 6-OHDA-injected rats. In vitro LiCI treatment decreased the toxicity of 6-OHDA on PC12 cells and prevented apoptosis. Additionally, LiCI treatment increased SOA activity, GSH-Px levels, and GSK-38-Ser9 phosphorylation; decreased MDA accumulation in the striatum and GS K-3 beta mRNA levels; as well as increased beta-catenin and cyclinD1 mRNA and protein levels in 6-OHDA-treated PC12 cells. Additionally, SDS treatment increased the protective effect of LiCI on 6-OHDA-treated PC12 cells. Conclusion: Evidence from experimental models suggested that SDS may confer neuroprotection against the neurotoxicity of 6-OHDA in response to OS injury and showed that these beneficial effects may be related to regulation of the Wnt/beta catenin signaling pathway. Therefore, SDS might be a potential therapeutic agent for treating PD. (C) 2018 The Author(s) Published by S. Karger AG, Basel