Neuroprotective Effects of Thymol-Loaded Selenium Nanoparticles against6-OHDA-Induced Apoptosis and Oxidative Stress in an In Vitro Parkinson's DiseaseModel

Introduction: Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons within the substantia nigra, leading to progressive motor dysfunction. There are still limited diseasemodifying options that counteract the process of disease progression. This study aimed to evaluate the neuroprotective effects of thymol, both in its free form and when loaded onto selenium nanoparticles (SeNPs), in a 6-hydroxydopamine (6-OHDA)-induced PD model using SH-SY5Y cells. Method: SeNPs were synthesized using a chemical reduction method with ascorbic acid, achieving a 68% entrapment efficiency for thymol. FTIR analysis suggested an interaction between thymol and selenium, which was confirmed by EDX analysis. Nano-Se-thymol particles were observed to be spherical, with a mean size of 135.7 nm and a negative surface charge. Results: Nano-Se-thymol exhibited low toxicity in normal fibroblast cells and demonstrated greater neuroprotective effects against 6-OHDA-induced cytotoxicity compared to thymol. Nano-Se-thymol significantly reduced ROS generation and increased cell viability compared to 6-OHDA. Furthermore, Nano-Se-thymol decreased the expression of NF-κB inflammatory markers and caspase-3 apoptotic proteins, which were elevated by 6-OHDA, compared to thymol alone. Discussion: Nano-Se-Thymol significantly attenuates 6-OHDA-induced cytotoxicity in an established in vitro model of PD. The neuroprotective efficacy of Nano-Se-Thymol is attributed to its enhanced antioxidant capacity, as evidenced by a significant reduction in ROS levels, along with its ability to inhibit apoptosis and modulate cell cycle progression. Conclusions: Nano-Se-thymol is a potential disease-modifying agent for the treatment of PD; however, further studies and long-term safety assessments are essential to confirm these benefits and understand the underlying mechanisms. conclusion: Our findings suggest that Nano-Se-thymol is a potential disease-modifying agent for the treatment of PD, however, further in vivo studies and long-term safety assessments is essential to confirm these benefits and to better understand the underlying mechanisms.