Network pharmacological analysis and experimental study of melatonin in chronic prostatitis/chronic pelvic pain syndrome

Abstract

Abstract Objective: This study aims to explore the potential mechanisms of melatonin (MT) in treating chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using network pharmacology and molecular docking. Methods: The target genes of MT were acquired from the Swiss Target Prediction, Superpred, SEA, and PharmMapper databases and the CP/CPPS targets were collected based on OMIM, Disgenet, and Genecards databases. The intersection of MT and CP/CPPS target genes was analyzed. A PPI network was constructed using Cytoscape to identify core targets. The shared targets underwent GO and KEGG enrichment analyses by Using R software. Molecular docking of MT with core targets was performed using AutoDock and PyMol. And using cell experiments to verify the potential effect of MT in CP/CPPS. Results: Network pharmacology analysis reveals 284 shared targets between MT and CP/CPPS, with AKT1, SRC, HSP90AA1, PTGS2, BCL2L1, ALB, CASP3, NFKB1, HIF1A, and ESR1 identified as key targets. Enrichment analysis indicates that MT affects CP/CPPS through various biological processes, and pathway analysis emphasizes the significance of PI3K-Akt, MAPK, Ras, FoxO, HIF-1, EGFR, and apoptosis pathways. Molecular docking confirms strong binding between MT and core targets. Cell experiments demonstrate that MT can inhibit the secretion of IL-1β, IL-6, and TNF-α in LPS induced RWPE-1 cells, alleviate inflammation, and suppress cell apoptosis and oxidative stress. Conclusion: Network pharmacology, molecular docking and cell experiments showed that MT could play a role in CP/CPPS by regulating multiple targets and pathways. This provides valuable insights for a more in-depth investigation into the molecular mechanisms and clinical applications of MT in CP/CPPS treatment.