Zanthoxylum armatum Essential Oil Attenuates MPP ⁺ ‐Induced Overexpression of Serine Palmitoyltransferase and Neurotoxicity in SH‐SY5Y Cell Culture Model of Parkinson's Disease: Evidence From In Vitro and In Silico Studies

Parkinson's disease (PD) is characterized by advanced neuronal degeneration, mitochondrial impairment, and aberrant lipid metabolism. Emerging evidence suggests that dysregulated sphingolipid biosynthesis, particularly through the upregulation of serine palmitoyltransferase (SPTLC1), contributes to the pathogenesis of PD. This study investigates the neuroprotective potential of Zanthoxylum armatum essential oil (ZAEO) in an MPP⁺-induced SH-SY5Y cell model of PD, focusing on modulation of SPTLC1 expression and associated neurotoxicity. GC-MS (Gas Chromatography-Mass Spectroscopy) analysis identified 28 phytoconstituents in ZAEO, accounting for 99.9% of its composition, with linalool (66.74%) and limonene (17.78%) as the principal components. ZAEO treatment significantly attenuated MPP⁺-induced cytotoxicity, restored neuronal nuclear marker NeuN (Neuronal nuclei), and notably suppressed the overexpression of SPTLC1, a key enzyme driving ceramide accumulation and mitochondrial stress in PD pathology. Immunofluorescence and cell viability assays corroborated these protective effects. Furthermore, molecular docking of ZAEO constituents with SPTLC1 (PDB ID: 7K0K) revealed high-affinity binding of minor compounds, including phellandral, humulene, and (-)-carvone, suggesting direct interactions with the enzyme and potential inhibition. These findings underscore the ability of ZAEO to mitigate neurodegeneration by modulating the sphingolipid axis and support its development as a multi-targeted phytotherapeutic strategy for Parkinson's disease.