Stigmasterol Alleviates Levodopa-Induced Dyskinesia in 6-OHDA-Induced Parkinsonian Rats

Chronic treatment with levodopa often leads to levodopa-induced dyskinesia (LID), around 40% of individuals are affected. Stigmasterol exhibits antioxidant, anti-inflammatory, and glutamate-antagonist properties, acting through AKT-1, VEGFR, and IL-6 to prevent neuronal death. This study investigates the STI potential to mitigate LID. Male Sprague Dawley rats were assigned to five groups (SHAM, 6-OHDA, LID, STI 10, STI 20), with n = 10. PD was induced by stereotaxic infusion of 6-OHDA (3 µg/µL × 2.5 µL) into the right medial forebrain bundle. After a 21-day recovery period, development of PD was confirmed through behavioral assessment, including APO-induced rotation, footprint analyses, and a stepping test assessment conducted over 7 days. Subsequently, the rats were treated with levodopa + carbidopa and stigmasterol (10/20 mg/Kg) orally for 28 days. Abnormal involuntary movements (AIMs) were assessed at intervals of 1, 14, 21, and 28th days to evaluate the effect of stigmasterol on LID. On day 28, rats were euthanized, and brain samples were analyzed for biochemical, and histopathological changes in the striatum and substantia nigra using nissl staining. STI treatment (10/20 mg/Kg) significantly decreased AIMS, MDA level, TNF-α, IL-1β, NF- kB, and NLRP3 and significantly increased GSH, SOD, catalase and dopamine levels. The histopathology assessment restored neurons in the striatum and substantia nigra of the brain. The result concludes that co-administration of stigmasterol (10/20 mg/Kg) with L-DOPA + carbidopa restores DA level, showing anti-inflammatory, anti-oxidant properties, and neuroprotective activity. Stigmasterol can therefore be administered as an adjuvant treatment to delay LID.