Sweet orange essential oil and (+)-limonene prevent oxidative stress, reduce inflammation, and apoptosis in differentiated SH-SY5Y neuroblastoma/BV-2 microglia co-culture neurodegeneration models.

BACKGROUND: Parkinson's disease (PD) is becoming increasingly prevalent worldwide. The pathophysiology of this condition is characterized by oxidative stress, inflammation, iron accumulation, mitochondrial dysfunction, and protein aggregation, all of which contribute to cell death and neurodegeneration. Microglia, the innate immune cells of the brain, play a significant role in the development and progression of PD by releasing inflammatory cytokines upon activation. Essential oils (EOs) are emerging as potential therapeutic agents because of their antioxidant and anti-inflammatory properties. METHODS: In our study, we investigated the antioxidant, anti-inflammatory, and anti-apoptotic effects of sweet orange [Citrus sinensis (L.) Osbeck (Rutaceae)] EO and its main compound (+)-limonene on monocultures of all-trans retinoic acid-differentiated and 6-hydroxydopamine-induced (6-OHDA) SH-SY5Y cells and bilaminar co-cultures containing differentiated and 6-hydroxydopamine-induced SH-SY5Y cells and BV-2 microglia. RESULTS: Sweet orange EO and (+)-limonene significantly decreased reactive oxygen species (ROS) production and increased oxidative stress defense by increasing the total antioxidant capacity and glutathione peroxidase and superoxide dismutase activities in human neuroblastoma (SH-SY5Y) cells. Additionally, both EO and its main compound mitigated inflammation by downregulating the secretion of pro-inflammatory cytokines. They also decreased the cytochrome c levels and caspase-3 activity. Furthermore, sweet orange EO and (+)-limonene attenuated microglia-mediated inflammation in co-cultures, suggesting their potential application as modulators of microglial activity. CONCLUSIONS: Based on these results, sweet orange EO and its main component, (+)-limonene, can be considered as neuroprotective agents and are promising candidates for complementary therapy in Parkinson's disease.