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

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. Purpose 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 anti-oxidant 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%. Anti-oxidant 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.