Virtual screening and molecular mechanism of novel anti-benign prostatic hyperplasia peptides from Syngnathus schlegeli.

Benign prostatic hyperplasia (BPH) is a common degenerative urinary system among old men. The marine pipefish (Syngnathus schlegeli) exhibited potential reproductive health benefits. However, its mechanisms and active components in alleviating BPH remain unclear. The S. schlegeli extract (SN, 200 mg/kg) prepared by enzymatic hydrolysis and ultrafiltration significantly reduced the prostate tissue weight 25 % approximately (p < 0.01) in a testosterone propionate (TP) induced BPH rat. Pathological analysis revealed a significant reduction in epithelial cell thickness and collagen fiber area (p < 0.001) and regulated serum dihydrotestosterone, prostate-specific antigen, 5α-reductase, pro-inflammatory factors, and oxidative stress markers. The transcriptomics, targeted-metabolomics, quantitative real-time polymerase chain reaction analysis (qRT-PCR), and western blotting (WB) assay revealed that SN alleviates BPH by binding to extracellular matrix receptor and inhibiting PI3K-Akt and NF-κB pathways. A peptide library constructed based on nano-LC-MS/MS identified 9209 peptides, and combined with network pharmacology and molecular docking, three highly active peptides (DGFR, LMDK, and KPF) were selected, and confirmed to inhibit the proliferation of TP-induced RWPE-1 cells with IC50 lower than RGD (Arg-Gly-Asp). Quantum chemical analyses indicated that the short peptide structures of N-terminal branched-chain, hydrophobic and polar amino acids contribute to anti-BPH activity. These findings suggest that SN may serve as a beneficial food functional supplement for improving the treatment of BPH patients.