Mulberrin attenuates 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-induced Parkinson's disease by promoting Wnt/β-catenin signaling pathway

Abnormal neuroinflammation and oxidative stress has been shown to cause neuronal loss in the progressive neurodegenerative Parkinson's disease (PD). Mulberrin is the key component of Ramulus Mori that has various biological activities. This study was to investigate the functions and mechanisms of mulberrin in PD. PD models were established by administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to Sprague Dawley rats in vivo and Lipopolysaccharide (LPS) treatment on microglial BV2 cells in vitro. Rota-rod test was applied to investigate the roles of mulberrin on MPTP-induced behavioral impairment. The effects of mulberrin on neuronal number and microglia activation were assessed by tyrosine hydroxylase (TH) immunohistochemistry and ionized calcium binding adaptor molecule-1 (Iba-1) immunofluorescence. Inflammatory cytokines and oxidative markers were measured by qRT-PCR. Wnt/β-catenin components were compared by Western blot. Mulberrin alleviated MPTP-induced impairment of motor coordination in a dose-dependent manner, and partially restored neuronal and microglial population. Neuroinflammation and oxidative stress were suppressed after mulberrin treatment both in vivo and in vitro. Wnt/β-catenin pathway was partially restored in BV2 cells. Finally, mulberrin rescued MPTP-induced abnormality in tracer elimination by MRI. Our study indicates that mulberrin is a potent suppressor of PD abnormalities and warrants further investigations in the clinical application of mulberrin for treating PD.