Therapeutic Potential of Pistachio Green Hull Extract in Treating Parkinson's Disease: A Comprehensive In Vivo and In Vitro Investigation

Pistachio green hull extract (PGHE), an agro-industrial by-product, is rich in phenolic compounds with significant inherent antioxidant and anti-inflammatory activities. In this study, the neuroprotective effects of PGHE against Parkinson's disease (PD), a progressive neurodegenerative disorder, were evaluated both in vivo and in vitro. The lethal dose (LD₅₀) of PGHE was greater than 5000 mg/kg, indicating its safety and nontoxicity. Rats were orally treated with PGHE (800 mg/kg/day) 24 h after injection of 6-OHDA (20 μg/rat in right MFB) for 14 days. Motor function was evaluated on Days 7 and 15 after 6-OHDA administration using the cylinder, narrow beam, pole, rotarod, and apomorphine-induced rotations tests. PGHE significantly improved motor impairments induced by 6-OHDA. An in vitro study indicated that increasing concentrations of PGHE up to 250 μg/mL resulted in a reduction in the aggregation of α-synuclein characterized by thioflavin T fluorescence and Congo red assays. Transmission electron microscopy images further confirmed a decrease in α-synuclein aggregation in the presence of PGHE. In conclusion, these findings indicated that PGHE improved motor deficits in a rat model of PD and decreased α-synuclein aggregation in vitro, suggesting that it can be considered a novel dietary supplement for PD therapy. However, more studies are needed to clarify the underlying mechanisms of PGHE's effect on PD pathogenesis and its potential applications in developing functional foods or nutraceuticals.