Abstract
BackgroundParkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by a loss of dopaminergic neurons in the substantia nigra, decreased striatal dopamine levels, and consequent extrapyramidal motor dysfunction. The purpose of this study was to investigate potential in vivo protective effects of Duzhong against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), as well as the bioactive constituents against 1-methyl-4-phenylpyridinium (MPP+) toxicity in vitro.MethodsMale C57BL/6 mice were intraperitoneally administrated five consecutive injections of MPTP every 24 h at a dose of 30 mg/kg to induce an in vivo PD model. Pole and traction tests were performed in mice to evaluate motor deficits and bradykinesia after the final MPTP administration. The striatal levels of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanilic acid, were measured using a High-performance liquid chromatography-electrical conductivity detector. To further explore the bioactive constituents and protective mechanisms of Duzhong, seven compounds from Duzhong were tested on MPP+-treated SH-SY5Y cell lines in vitro. A proteasome enzymatic assay and Cell Counting Kit-8 were performed to examine proteasomal activity and cell viability of Duzhong-treated cells, respectively, after exposure to MPP+ and proteasome inhibitor MG132.ResultsDuzhong antagonized the loss of striatal neurotransmitters and relieved the associated anomaly in ambulatory locomotor activity in PD mice after a 3-day pre-treatment of Duzhong crude extract. The five Duzhong compounds attenuated MPP+-induced dysfunction of protease activity and reduced MG132-induced cytotoxicity.ConclusionDuzhong could serve as a potential candidate for PD treatment, and its mechanism involves the amelioration of the ubiquitin-proteasome system.
Highlights
Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by a loss of dopaminergic neurons in the substantia nigra, decreased striatal dopamine levels, and consequent extrapyramidal motor dysfunction
Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease. It affects people aged over 55 years with psychological and physical manifestations [1, 2]. It is marked by the extensive loss of dopaminergic neurons in the substantia nigra, which result in extrapyramidal motor dysfunction, including tremor, rigidity, and bradykinesia [3]
Prophylactic treatment with Duzhong (150, 300, and 600 mg/kg) shortened the time needed to reach the platform, and results showed that 600 mg/kg was the most effective (Fig. 2a). These results suggested that Duzhong prevented MPTP-induced bradykinesia
Summary
Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by a loss of dopaminergic neurons in the substantia nigra, decreased striatal dopamine levels, and consequent extrapyramidal motor dysfunction. Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease It affects people aged over 55 years with psychological and physical manifestations [1, 2]. It is marked by the extensive loss of dopaminergic neurons in the substantia nigra, which result in extrapyramidal motor dysfunction, including tremor, rigidity, and bradykinesia [3]. Impairment of the UPS is a cellular mechanism underlying the neurodegenerative process of PD It is characterized by the substitution of a highly soluble native neuronal protein with a progressively polymerized protein, which forms to an altered conformation. The abnormal or misfolded proteins are normally targeted via ubiquitination to the proteasome, where they are degraded in an adenosine triphosphate-dependent manner
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