New insights into anti-hyperuricemic effects of novel peptides from Antarctic Krill (Euphausia superba) by Q-Exactive Orbitrap MS-based non-targeted metabolomics

Hyperuricemia (HUA) endangers renal function and induces gout. Although peptides from Antarctic Krill (AKP) showed anti-hyperuricemic effects, the underlying mechanism remained unclear. The study investigated the antihyperuricemic effect via xanthine oxidase (XOD) inhibitory activity, an adenosine-induced HK-2 cell model, and a potassium oxonate (PO)-induced mouse model. The AKP prepared using alkaline protease exhibited a strong XOD inhibitory activity with a low IC50 value of 3.232 mg/mL. AKP (5 mg/mL) reduced the uric acid (UA) content by 40.50% in HK-2 cells (p < 0.01). In addition, AKP (600 mg/kg/d) reduced serum UA level by 54.37% in a mouse model (p < 0.01) and had an alleviating effect on HUA-induced inflammation. Besides, AKP supplementing could regulate the mRNA levels of renal UA urate transporters (GLUT9, ABCG2, OAT1, OAT3, and NPT1) to promote UA excretion. According to non-targeted metabolomics, AKP regulated metabolic disorders in HUA mice by proximal tubule bicarbonate reclamation, taurine and hypotaurine metabolism, and butanate metabolism, etc, providing useful clues for research on the molecular mechanism of AKP. In addition, AKP alleviated gout by reducing paw swelling and inflammatory factors (IL-6, TNF-alpha, IL-1 beta) levels.