Polygonatum cyrtonema polysaccharide alleviates dopaminergic neuron apoptosis in Parkinson's disease mouse model via inhibiting oxidative stress and endoplasmic reticulum stress

Parkinson's disease (PD) has become a global health threat as a progressive neurodegenerative disorder. Polygonatum cyrtonema polysaccharide (PCP), the main bioactive constituent in P. cyrtonema rhizome, displays various biological activities. However, its antiparkinsonian effect is elusive. Here, the effect of PCP on PD-like pathology was evaluated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and its molecular mechanism was further investigated. The results showed that PCP at different dosages significantly improved MPTP-induced weight loss and dyskinesia in PD mice. Moreover, PCP treatment mitigated the dopaminergic neuron loss in the substantia nigra pars compacta (SNc). Analysis of apoptosis-related proteins revealed that PCP markedly decreased the expression levels of Bax and cleaved-caspase 3, and increased the expression level of Bcl-2 in PD mice. Meanwhile, PCP markedly enhanced the activities of antioxidant enzymes superoxidase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), reduced malondialdehyde (MDA) content, and reversed the expression of oxidant stress-related proteins Nrf2 and Keap1, in the SNc of PD mice. Furthermore, PCP treatment significantly reduced the MPTP-mediated increase of endoplasmic reticulum (ER) stress-related proteins. These findings suggest that PCP protects against PD-like pathology by mitigating oxidant stress and ER stress-mediated apoptosis of dopaminergic neurons, highlighting its potential as a therapeutic agent for PD.