Neuroprotective potential of lycopene in traumatic brain injury: Insights from network pharmacology and molecular docking

PURPOSE: Traumatic brain injury (TBI) is a leading cause of mortality and long-term disability worldwide, with no effective pharmacological interventions. This study investigates the neuroprotective potential of lycopene, a carotenoid with antioxidant and anti-inflammatory properties, using network pharmacology and molecular docking in TBI. MATERIALS AND METHODS: Potential targets of lycopene were identified using SwissTargetPrediction and GeneCards, while TBI-associated genes were retrieved from Online Mendelian Inheritance in Man and GeneCards. The intersection between compound and disease targets was analyzed through protein-protein interaction (PPI) networks, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The top 10 hub genes from the PPI network were selected for molecular docking using AutoDock Vina to evaluate lycopene's binding affinity. RESULTS: A total of 210 overlapping lycopene - TBI targets were identified. PPI analysis revealed ten hub genes implicated in neuroinflammation, apoptosis, lipid metabolism, oxidative stress, and neuronal survival. Enrichment analyses highlighted pathways related to cytokine signaling, lipid homeostasis, AGE-RAGE signaling, HIF-1 signaling, and epidermal growth factor receptor (EGFR)-mediated neuroprotection. Molecular docking demonstrated strong binding affinities of lycopene, particularly with EGFR, Peroxisome Proliferator-Activated Receptor Gamma, ALB, TP53, and ESR1. CONCLUSION: These findings suggest that lycopene exerts multi pathway neuroprotection in TBI by simultaneously targeting inflammatory mediators, apoptotic regulators, metabolic sensors, lipid homeostasis pathways, and pro survival receptors in TBI through multi target mechanisms by targeting key hub proteins, offering a potential advantage over single target strategies. Lycopene demonstrates multi-pathway neuroprotective potential in TBI, warranting further in vitro and in vivo validation for clinical translation.