The hypouricemic effect and mechanism of tuna (Thunnus albacares) peptide and screening its functional peptide segments.

This study aimed to examine the hypouricemic effect of tuna peptide (TP) and its potential mechanisms in hyperuricemia (HUA) mice. Additionally, functional TP segments were screened to identify the bioactive components. The results revealed that TP mitigated HUA by inhibiting serum and hepatic xanthine oxidase (XOD) activity and suppressing the expression of urate transporters, including renal glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) in the kidneys, and GLUT9 in the ileum. TP also significantly lowered the serum urea nitrogen (BUN) and creatinine (CR) levels and alleviated inflammatory damage to the liver and kidneys. Moreover, ten potentially active peptide segments were identified by LC-MS/MS and molecular docking analyses. The in vitro XOD inhibitory activities of the active peptide segments (the tetrapeptide LILP and tripeptides LFP and LAF) were greater than that of TP, and their treatment also significantly reduced UA levels and suppressed the mRNA expression of URAT1 and GLUT9 in a human kidney-2 (HK-2) cell model. These results suggest that TP, as well as its active peptide segments, LILP, LFP and LAF, could be suitable as effective functional ingredients to combat HUA.