Anti-hyperuricemic peptides derived from bonito hydrolysates based on in vivo hyperuricemic model and in vitro xanthine oxidase inhibitory activity

Abstract

Traditional drugs used to treat hyperuricemia have adverse effects. In this study, to identify safer anti-hyperuricemic bioactive peptides isolated from food-derived protein hydrolysates, a hyperuricemia rat model induced by potassium oxonate (PO) was used to evaluate the activity of bonito hydrolysates (BH), dephenolised walnut hydrolysates (DWH), and soybean hydrolysates (SH). The serum uric acid level of rats in the BH group (95.4 ± 27.4 μM, p < 0.01) was significantly reduced compared to that in the model group (212.00 ± 30.00 μM) to a level even lower than that in allopurinol group (114.3 ± 53.0 μM). Furthermore, BH alleviated renal impairment caused by PO in vivo and exhibited the greatest xanthine oxidase (XOD) inhibitory activity (65.5 ± 8.0%) in vitro compared to the other hydrolysates. Two peptides identified from BH bound the catalytic site of XOD, among which the hydrophobic peptide WML entered the active site of XOD more easily compared to the hydrophilic peptide PGACSN, possibly because of hydrophobic interactions. The chemically synthesized WML demonstrated high XOD inhibitory effect compared to PGACSN and a significant change in the secondary structure of XOD. Therefore, hexapeptide PGACSN and tripeptide WML are partially responsible for the anti-hyperuricemic activity of BH, and hydrophobic amino acids play important roles in the XOD inhibitory activity of peptides.

Keywords: Bioactive peptides; Hyperuricemia; Molecular docking; Protein hydrolysates; Xanthine oxidase.