Network Pharmacology Analysis of Lycopene to Identify Its Targets and Biological Effects in Human Tissues

Background: Lycopene exhibits a broad spectrum of biological activities with potential therapeutic applications. Despite its established antioxidant and anti-inflammatory properties, the molecular basis for its pharmacological actions remains incompletely defined. Here we investigated the molecular targets, pharmacodynamic feasibility, and tissue-specific expression of lycopene targets using a network pharmacology approach combined with affinity and protein-protein interaction (PPI) analyses. Methods: Lycopene-associated human protein targets were predicted using Swiss target screening platform. Molecular docking was used to estimate binding affinities, and concentration-affinity (CA) ratios were calculated based on physiologically relevant plasma concentrations (75–210 nM). PPI networks of lycopene targets were constructed to identify highly connected targets, and tissue expression analysis was assessed for high-affinity targets using protein-level data from the Human Protein Atlas database. Results: Of the 94 predicted targets, 37% were nuclear receptors and 18% were Family A GPCRs. Among the top 15 high-affinity targets, nuclear receptors and GPCRs comprised 40% and 26.7% respectively. Twenty targets had affinities 1). PPI analysis revealed 32 targets with high interaction and 9 with significant network connectivity. Seven targets (TRIM24, GRIN1, NTRK1, FGFR1, NTRK3, CHRNB4, and PIK3CD) showed both high affinity and centrality in the interaction network. Expression profiling of submicromolar targets revealed widespread tissue distribution for MAP2K2 and SCN3A, while SCN2A, TOP2A, and TRIM24 showed more restricted expression patterns. Conclusion: This integrative analysis identifies a subset of lycopene targets with both high affinity and pharmacological feasibility, particularly MAP2K2, SCN2A, and TRIM24. Lycopene appears to exert its biological effects through modulation of interconnected signalling networks involving nuclear receptors, GPCRs, and ion channels. These findings support the potential of lycopene as a multi-target therapeutic agent and provide a rationale for future experimental and clinical validation.