An Investigation of the Protective Effects of Trifolirhizin against MPTP-induced Parkinson’s Disease in Mice

ABSTRACT

Background: Parkinson’s disease (PD) is a prevalent age-associated neurodegenerative disorder, primarily characterized by dopaminergic neuronal loss, oxidative stress, and microglia-mediated neuroinflammation. Current therapies offer limited relief and are often associated with adverse effects, necessitating the development of safer, more effective alternatives. Objectives: This study aimed to investigate the neuroprotective effects of trifolirhizin (TF), a natural flavonoid, in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. Materials and Methods: Male C57BL/6 mice were administered MPTP to induce PD-like symptoms, followed by treatment with TF. Behavioral assessments (wire hang and open field tests) evaluated motor function. Biochemical assays measured oxidative stress markers malondialdehyde (MDA), monoamine oxidase-A (MAO-A) activity, and antioxidant enzyme levels. Pro-inflammatory cytokines (interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6) were quantified, and histopathological analysis of the substantia nigra was performed. Results: TF-treated mice showed a 48% improvement in rotarod performance and a significant increase in exploratory behavior compared to MPTP-only controls. MDA levels were reduced by 41%, while MAO-A activity was suppressed by 35%. Antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT)) were markedly upregulated. Notably, the TF treatment led to a greater than 50% reduction in pro-inflammatory cytokines and preserved the structural integrity of dopaminergic neurons, as confirmed by histological evaluation. Conclusion: TF significantly improves motor function, mitigates oxidative damage, suppresses neuroinflammation, and protects dopaminergic neurons in MPTP-induced PD mice. These findings underscore TF’s potential as a promising therapeutic candidate for slowing PD progression and alleviating its symptoms.

KEYWORDS

• Parkinson’s disease
• trifolirhizin
• 1-methyl-4-phenyl-1
• 2
• 3
• 6-tetrahydropyridine
• dopaminergic neurons
• oxidative stress
• mouse models

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• DOI10.1177/09731296251362609Copy

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