What question did this study set out to answer?

The study aims to identify peptides with xanthine oxidase inhibitory activity through fermentation of salmon and evaluate their effects on hyperuricemia in kidney cells.

February 28, 2026Open Access

XOD inhibition peptides obtained via fermentation of Salmon by Bacillus amyloliquefaciens and evaluation of their anti-hyperuricemia mechanism in HK-2 cells

Key Points

The study aims to identify peptides with xanthine oxidase inhibitory activity through fermentation of salmon and evaluate their effects on hyperuricemia in kidney cells.
Fermentation of salmon dark meat using Bacillus amyloliquefaciens Y11.
Isolation of peptides via ultrafiltration and Sephadex G15 chromatography.
Identification of peptides using liquid chromatography with tandem mass spectrometry.
In vitro evaluation of the hypouricemic effects of selected peptides in HK-2 cells.
Molecular docking analysis to assess the inhibitory mechanisms of peptides.
GEADFMDYGR and its truncated peptide GEADF showed high xanthine oxidase inhibitory activity in vitro.
At 0.5 mg/mL, GEADFMDYGR decreased uric acid levels by 39.70 ± 8.75 μmol/L in HK-2 cells.
GEADF decreased uric acid levels by 27.43 ± 3.31 μmol/L in HK-2 cells.
Both peptides function as reversible mixed-type xanthine oxidase inhibitors.

Abstract

Hyperuricemia (HUA) is a metabolic disorder that can trigger gout and cause renal dysfunction. In this study, microbial fermentation with Bacillus amyloliquefaciens Y11 was employed to ferment salmon dark meat. Subsequently, novel peptides with high xanthine oxidase (XOD) inhibitory activity were derived from the fermented samples, purified, and identified. The hypouricemic effect of these peptides was evaluated using an in vitro HK-2 cell HUA model. Five fractions (G1–G5) were isolated via ultrafiltration and Sephadex G15 gel chromatography, and the fractions with higher XOD inhibition rates (G1 and G5) were combined to prepare a mixed fraction. Subsequently, 4122 peptides were identified from the mixed fraction using liquid chromatography with tandem mass spectrometry. Based on predictive bioactivity, toxicity, allergenicity, and solubility scores, five peptides and seven corresponding truncated peptides were selected for synthesis. Their XOD inhibitory activity was assessed, and molecular docking analysis was performed. Ultimately, GEADFMDYGR and its truncated peptide GEADF, which showed high XOD inhibitory activity in vitro (inhibition rates of 90.72 ± 2.85% and 94.06 ± 1.30%, respectively), were screened out. In the HK-2 HUA model, both peptides significantly reduced intracellular uric acid levels. Specifically, 0.5 mg/mL GEADFMDYGR and GEADF decreased the uric acid levels in these cells by 39.70 ± 8.75 and 27.43 ± 3.31 μmol/L, respectively. Further analyses revealed that GEADFMDYGR and GEADF are reversible mixed-type XOD inhibitors. These findings provide new insights and experimental evidence guiding the development of novel therapeutic peptides for HUA. • Novel XOD inhibitory peptides were obtained from salmon using Bacillus amyloliquefaciens fermentation. • GEADFMDYGR and its truncated peptide GEADF, which showed high XOD inhibitory activity in vitro. • 0.5 mg/mL GEADFMDYGR and GEADF decreased the uric acid levels in HUA cells by 39.70 ± 8.75 and 27.43 ± 3.31 μmol/L, respectively.

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