In Silico Study of Argan Oil Metabolites: Evaluation of Their Potential to Inhibit Key Receptors Activated by Excessive Alcohol Consumption and Involved in Cell Death

Excessive alcohol consumption is a well-established cause of liver injury and neurodegeneration, driven by oxidative stress, inflammation, and apoptosis. This study explores the potential of Argania spinosa (argan oil) metabolites as natural inhibitors of key receptors involved in alcohol-induced cellular damage: NOX4 (NADPH Oxidase 4), PARP (Poly ADP-ribose Polymerase), and CCR2 (C-C Motif Chemokine Receptor 2). Using in silico approaches, including molecular docking, ADMET analysis, and molecular dynamics simulations, we systematically evaluated the interactions between twenty previously reported argan oil metabolites and these receptors. Among the analyzed compounds, spinasterol emerged as the most promising bioactive molecule, demonstrating high binding affinity and structural stability within the receptor active sites. Molecular interaction analysis revealed strong hydrophobic interactions, π-π stacking, and hydrogen bonding, contributing to receptor inhibition. These findings suggest that spinasterol could modulate inflammatory and oxidative pathways, reducing alcohol-induced cellular stress. This study underscores the potential of argan oil metabolites as natural therapeutic agents for preventing and mitigating alcohol-related pathologies. Future in vitro and in vivo investigations are necessary to validate these computational results and explore the translational potential of these compounds in clinical settings. The findings contribute to advancing plant-based drug discovery and natural pharmacological interventions for alcohol-induced disorders.