Investigation of the neuroprotective effects of natural terpenes delivered to cells via a niosomal transport system in an experimental parkinson's disease model

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, with a prevalence reaching 2–3% in individuals over the age of 65, and for which no curative treatment is currently available. Existing therapeutic approaches are primarily aimed at symptomatic management and have limited effects on pathogenic mechanisms such as oxidative stress, mitochondrial dysfunction, and protein aggregation. Therefore, the development of neuroprotective agents and their effective delivery to target cells are of great importance. The aim of this thesis is to quantitatively evaluate the neuroprotective effects of naturally derived terpenes delivered to cells via niosomal carrier systems in an experimental in vitro model of Parkinson's disease. In this study, the SH-SY5Y cell line was differentiated into a dopaminergic phenotype, and a neurotoxicity model was established by the application of MPP⁺ at its IC₅₀ concentration. As a result of MPP⁺ treatment, cell viability decreased from 100% in the control group to 42.6 ± 3.8% (p < 0.001). While the application of natural terpenes in their free form increased cell viability to 61.4 ± 4.2%, the application of the same terpenes following niosomal encapsulation elevated viability to 78.9 ± 3.1%. A statistically significant difference was observed between the niosomal terpene group and the MPP⁺ group (p < 0.001). In terms of oxidative stress parameters, MPP⁺ treatment increased total oxidant status (TOS) to 18.6 ± 1.9 µmol H₂O₂ equivalent/L, whereas niosomal terpene treatment reduced this value to 9.2 ± 1.3 (p < 0.01). Similarly, total antioxidant capacity (TAC) was 0.82 ± 0.07 mmol Trolox equivalent/L in the MPP⁺ group and increased to 1.74 ± 0.11 in the niosomal terpene group (p < 0.001). In conclusion, it was demonstrated that natural terpenes delivered to cells via niosomal carrier systems exhibit increased intracellular bioavailability compared to their free forms, significantly reduce MPP⁺-induced neuronal cytotoxicity, and suppress oxidative stress parameters. These findings indicate that niosome-based natural compounds may offer a potential novel neuroprotective nano-therapeutic approach for Parkinson's disease.