Oyster hydrolysate via 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 via 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 in vitro 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 via 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.