Identification, In Silico Selection, and Mechanistic Investigation of Anti‐Prostatic Hyperplasia Peptides From <i>Syngnathus schlegeli</i>

Pipefish is traditionally used as a male tonic in China. Recent studies have shown 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 via network pharmacology, molecular docking, and quantum chemical techniques. SN4, a gel-separated fraction from the neutral enzymatic hydrolysates of S. schlegeli, contains 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 revealed that the peptides (FVDW and FIFE) were potentially active. In silico docking and quantum chemistry revealed that the N-terminal Phe linked to Ile/Val in FVDW and FIFE interacted with the AKT1, ITGB3, and SRC proteins, enhancing ligand-receptor interactions and affinity and highlighting their potential for improving BPH.