Identification and computational chemistry analysis of anti-prostatic hyperplasia peptides from Syngnathus schlegeli

Pipefish is traditionally used in Chinese folklore as a male tonic. Recent studies show that Syngnathus schlegeli extracts effectively combat benign prostatic hyperplasia (BPH). However, the specific active compounds involved and their mechanisms of action are not fully understood. This study aimed to investigate how pipefish peptides alleviate BPH using network pharmacology, molecular docking, and quantum chemical techniques. SN4, a gel-separated fraction from the neutral enzymatic hydrolysates of S. schlegeli, reveal 3470 peptide sequences, predominantly tetrapeptides enriched in Phe, Trp, Leu, and Ile. Network pharmacology identified SRC, AKT, and ITGB3 as primary targets. Molecular docking and in vitro tests on TP-induced RWPE-1 cell proliferation showed that peptides (FVDW, FIFE) were potentially active. In silico docking and quantum chemistry analysis showed that the N-terminal Phe linked to Ile/Val in FVDW and FIFE interacted with AKT1, ITGB3, and SRC proteins, enhancing ligand-receptor interactions and affinity, also highlighting their potential for improving BPH.