Oyster hydrolysate <i>via</i> dynamic enzymolysis ameliorates male sexual dysfunction in mice

Male sexual dysfunction (MSD) poses a substantial global health burden, with current pharmacotherapies often limited by adverse effects, necessitating safer, natural alternatives. This study investigates the therapeutic potential of oyster enzymatic hydrolysate (OEH) produced <i>via</i> an optimized dynamic enzymolysis membrane reactor (DEMR) for ameliorating MSD. The DEMR process enhanced OEH yield by 15.9% and antioxidant capacity by 42.8% compared to conventional methods, producing a hydrolysate rich in small peptides (<1000 Da), essential amino acids, taurine, and zinc with potent <i>in vitro</i> antioxidant and immunomodulatory activities. In an adenine/estradiol benzoate-induced MSD mouse model, DEMR-OEH intervention (1500 mg kg^-1) significantly restored sexual performance parameters to levels comparable to sildenafil. This efficacy was underpinned by a multi-mechanistic action: alleviating testicular oxidative stress <i>via</i> increased SOD/GSH activity and reduced MDA content, improving renal function indicated by decreased BUN/sCr levels, and normalizing endocrine homeostasis through the upregulation of serum testosterone and luteinizing hormone. Bioinformatic analysis further suggested involvement of oxytocin and cGMP-PKG signaling pathways. Our findings establish DEMR-derived OEH as a promising natural therapeutic agent for MSD, functioning through integrated antioxidant, renoprotective, and endocrine-modulating pathways.