Lycopene's therapeutic mechanisms in epididymitis: a network pharmacology and experimental study

Epididymitis, a common disease of the male reproductive system, is often caused by nonspecific infections. Antibiotics alone cannot reverse histopathological changes or prevent long-term reproductive issues. Lycopene (LYC), a potent antioxidant, has shown potential in alleviating epididymitis, yet its specific mechanisms remain unclear. This study used network pharmacology and in vivo experiments to explore LYC's mechanisms in treating epididymitis.

Epididymitis- and LYC-related target proteins were identified from multiple databases and analyzed using the Venny platform. Protein interactions were examined with the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and key targets were identified via topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted using the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Target-pathway networks were visualized in Cytoscape, molecular docking was performed with AutoDock Vina, and LYC's effects were validated in a lipopolysaccharide (LPS)-induced epididymitis mouse model.

Network pharmacology results indicated that LYC's effects involve the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, which plays a crucial role in regulating inflammation and apoptosis. In vivo, LYC improved epididymal pathology, reduced inflammatory cell infiltration, and decreased key inflammatory cytokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). By inhibiting PI3K/AKT activation, LYC modulated inflammation and reduced apoptosis. Additionally, LYC enhanced antioxidant enzyme activity and elevated the B-cell lymphoma-extra large (Bcl-xL) ratio, reducing oxidative stress and apoptosis. Molecular docking supported these findings, showing strong binding affinities with PI3K/AKT pathway targets.

This study highlights LYC's potential as an adjunctive treatment for epididymitis, targeting inflammation and oxidative stress via the PI3K/AKT pathway. These findings suggest that LYC could enhance current therapies and provide new options for the clinical management of epididymitis.