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

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, anti-inflammatory, antibacterial, and anticancer properties.

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.

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.

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.

Based on in vitro assays and in silico analyses, processed Citrus reticulata peel extracts may exert beneficial effects in both prostate cancer and benign prostatic hyperplasia. The soil-processed water extract demonstrated the most significant potential. The results suggest that the major compounds may act on several key proteins and pathways related to apoptosis and inflammation. However, further experimental and in vivo studies are needed to confirm their efficacy and safety.

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.