Integrated Molecular Docking and In Vitro Neuroprotective Assessment of p-Cymene in SH-SY5Y Cells

Abstract

Natural bioactive compounds continue to attract scientific attention due to their safety, accessibility, and broad therapeutic potential. Among these, monoterpenes present in essential oils have shown promising pharmacological activities, including neuroprotective effects. The present study aimed to evaluate the neuroprotective potential of pcymene, a widely distributed monoterpene, using in silico molecular docking and in vitro neuroprotective assessment in SH-SY5Y cells. Molecular docking was performed using AutoDock against selected target proteins to understand binding affinity and interaction patterns. The docked phytochemicals exhibited binding energies ranging from −6.4 to −9.6 kcal/mol, indicating favorable interactions primarily mediated through van der Waals and alkyl forces, suggesting potential modulation of protein activity through non-covalent interactions. For experimental validation, neuroprotection was assessed using the MTT assay in SH-SY5Y cells exposed to increasing concentrations of pcymene (1–10 mg/mL). The results demonstrated a clear dose-dependent response. Lower concentrations to medium concentrations (1 and 7 mg/mL) showed increased cell viability compared to control, indicating possible enhancement of mitochondrial activity or adaptive cellular responses. However, a slight decline in cell viability was observed at higher concentrations, with slightly lesser neuroprotective effects at 10 mg/ml. Overall, the study highlights the biphasic biological behavior of p-cymene, characterized by non-toxic or mildly stimulatory effects at low concentrations and pronounced cytotoxicity at higher doses. These findings support the potential of p-cymene as a bioactive compound with concentration-dependent therapeutic relevance, warranting further mechanistic and preclinical investigations