Natural Polyphenols Versus Standard Therapy: Effects on Neuroinflammation and Alpha-Synuclein Expression in a 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP)-Induced Mouse Model of Parkinson’s Disease

Background Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss, α-synuclein aggregation, and chronic neuroinflammation. While levodopa (L-DOPA) + carbidopa remains the cornerstone of symptomatic management, long-term use is associated with motor complications, prompting interest in adjunctive therapies targeting non-dopaminergic mechanisms. Polyphenolic compounds such as resveratrol and curcumin have demonstrated neuroprotective potential through antioxidant and anti-inflammatory actions. This study aimed to comparatively evaluate the effects of L-DOPA + carbidopa, resveratrol, curcumin, and their combination, resveratrol + curcumin, on motor function and biochemical markers in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Methodology An experimental study was conducted using 36 adult female C57BL/6 mice randomly allocated into six groups (<i>n</i> = 6): normal control group, MPTP group, L-DOPA + carbidopa group, resveratrol group, curcumin group, and resveratrol + curcumin group. PD was induced using intraperitoneal injection of MPTP (30 mg/kg/day for five days). Treatments were administered orally for 30 days. Motor coordination and locomotor activity were assessed using the rotarod test and open field tests at baseline (Day 0), post-MPTP induction (Day 6), and at the end of treatment (Day 37). Biochemical analysis of brain homogenates was performed to estimate α-synuclein and tumor necrosis factor-alpha (TNF-α) levels using enzyme-linked immunosorbent assay (ELISA). Statistical analysis was conducted using one-way analysis of variance (ANOVA) followed by Tukey's post hoc test. Results MPTP administration resulted in significant motor impairment, elevated α-synuclein accumulation, and increased TNF-α levels compared with controls (<i>P</i> < 0.001). L-DOPA + carbidopa produced the greatest improvement in rotarod and open field performance and significantly reduced both α-synuclein and TNF-α levels. Resveratrol and curcumin monotherapy significantly improved motor performance and attenuated biochemical alterations compared with the MPTP group (<i>P</i> < 0.001 ), with resveratrol showing greater efficacy than curcumin. Combined treatment with resveratrol and curcumin resulted in superior motor recovery and greater reductions in α-synuclein and TNF-α levels than either compound alone. Conclusions The findings demonstrate a close association between motor dysfunction, α-synuclein accumulation, and neuroinflammation in MPTP-induced PD. L-DOPA+ carbidopa remains the most effective intervention for motor and biochemical parameters. However, resveratrol and curcumin, particularly in combination, exhibit significant neuroprotective effects and may serve as promising adjunctive strategies targeting disease-related inflammatory and synuclein-mediated pathways. These results support further investigation of polyphenolic compounds as complementary therapies in PD.