Effect of Decoction on Movement Disorder and Substantia Nigra Dopaminergic Neurons in Mice with Chronic Parkinson's Disease.

This study aimed to explore the protective effects of decoction on dopaminergic (DA) neuron injury in a rotenone-induced mouse model with chronic Parkinson's disease (PD) and explore its mechanism of action. Ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to measure the content of six main components in the decoction. The chronic PD mouse model was established by treating 10-month-old healthy wild C57BL/6 male mice with rotenone 30 mg/kg/day for 28 days in succession. The pole test and rotarod test were applied to detect the rescue effect of decoction in high, medium, and low dosages, respectively, on PD-like behaviors in mice with chronic PD. The protective effect of decoction on the mesencephalic nigrostriatal DA neuron injury was determined employing tyrosine hydroxylase (TH) immunofluorescence staining. Enzyme-linked immunosorbent assay (ELISA) was adopted to measure the inflammatory cytokines in serum, including TNF- (tumor necrosis factor-alpha), IFN- (interferon gamma), NF-B (nuclear factor kappa-B), and IL-1 (interleukin-1 beta). Western blotting was performed to quantify the expression of phosphorylated -Jun N-terminal kinase (-JNK), cleaved caspase-3, B-cell lymphoma-2 (Bcl-2), and NF-B in the brain. Our results showed that the decoction in high, medium, and low dosages reduced the turning time of mice ( < 0.01, < 0.01,  and  < 0.05). The high and medium dosages shortened the total climbing time of PD mice in the pole test ( < 0.01 and  < 0.05). Meanwhile, the high, medium, and low dosages increased the rod-standing time of PD mice in the rotarod test ( < 0.01, < 0.05,  and  < 0.05). Besides, the decoction reversed the decrease in TH-positive neurons induced by rotenone, upregulated TH protein expression, and downregulated the -syn expression in the PD model. Moreover, the decoction in high dosage significantly inhibited the expression of -JNK, cleaved caspase-3, and NF-B in the midbrain of PD mice ( < 0.05, < 0.05,  and  < 0.01), upregulated the expression of Bcl-2 ( < 0.05), and decreased the content of TNF-, IFN-, NF-B, and IL-1 in the serum ( < 0.001, < 0.001, < 0.001,  and  < 0.001). Taken together, the decoction could protect mice from rotenone-induced chronic PD, which might be related to the reduction of the DA neuron apoptosis via suppressing the inflammatory reaction and the neuronal apoptosis pathway.