Neuroprotective Effects of the Combination of Green Tea, Saffron, Docosahexaenoic Acid, and α-Lipoic Acid in an In Vitro Model of Parkinson's Disease

Parkinson's disease (PD) is a neurodegenerative disorder characterised by dopamine deficiency and the accumulation of α-synuclein (α-syn), which aggregates into pathological inclusions known as Lewy bodies and Lewy neurites, distributed across multiple brain regions, with a particular prevalence in dopaminergic neurons. Alongside hallmark motor symptoms, PD is often accompanied by non-motor manifestations that severely affect patients' quality of life. Levodopa remains the most effective therapy; however, it is associated with a wide range of side effects and shows little to no efficacy against non-motor symptoms. This study investigates the neuroprotective effects of a combination of four bioactive compounds-green tea, saffron, docosahexaenoic acid (DHA) and α-lipoic acid (ALA)-against the PD-related neurodegeneration. Their ability to cross the blood-brain barrier (BBB) while maintaining its integrity was evaluated using a validated in vitro model. Individual and combined effects of these compounds were assessed on mesencephalic dopaminergic cells exposed to 6-hydroxydopamine (6-OHDA), a widely used in vitro model of PD-like neurotoxicity. The results demonstrated that the combined treatment (Mix) significantly restored cell viability after 6-OHDA exposure and more effectively reduced oxidative and nitrosative stress, as well as lipid peroxidation, compared to single compounds. Furthermore, the Mix markedly decreased the production of pro-inflammatory cytokines (including tumour necrosis factor-alpha (TNF-α) and interleukins) and downregulated the expression of PTEN-induced kinase 1 (PINK1) and Parkin, two key markers of PD-related neurodegeneration. In conclusion, these results indicate that the Mix has a suggest a synergistic-like impact on various disease-causing pathways in PD, highlighting its promise as a multi-faceted neuroprotective approach.