Exploring the Therapeutic Potential of Processed Citrus reticulata Peel Extracts in the Treatment of Prostate Cancer and Benign Prostatic Hyperplasia.

BACKGROUND

Citrus reticulata (CR) has a long-standing role in traditional medicine, primarily due to its bioactive constituents such as hesperidin and narirutin, which are known for their antioxidant, antiinflammatory, antibacterial, and anticancer properties.

OBJECTIVE

This study investigates the anti-proliferative activity of CR water extracts against DU-145 prostate cancer cells and explores the therapeutic potential and underlying molecular mechanisms of hesperidin and narirutin in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) through network pharmacology and molecular docking approaches.

METHODS

Cytotoxicity assays were employed to determine the anti-cancer efficacy (IC50) of processed CR water extracts in DU-145 cells. Targets related to hesperidin, narirutin, PCa, and BPH were identified using bioinformatics platforms. Network pharmacology was applied to construct compound-target interaction networks and perform enrichment analyses (GO, KEGG, and DisGeNET) to elucidate key signalling pathways. Molecular docking was conducted to validate compound-target interactions.

RESULTS

Soil-processed CR extracts exhibited the strongest anti-cancer activity (IC50 = 1.789 mg/mL). Enrichment analyses identified significant pathways, including AGE-RAGE signalling, p53 signalling, inflammation, angiogenesis, and apoptosis. Molecular docking confirmed strong binding affinities of hesperidin and narirutin to the predicted targets.

CONCLUSION

Anti-proliferative assays, network pharmacology, and molecular docking collectively demonstrate that hesperidin and narirutin from CR show strong therapeutic potential against PCa and BPH. The findings highlight the involvement of AGE-RAGE and p53 signalling pathways and support the potential of these compounds in future drug development.