Abstract
Hyperuricemia arises from imbalanced uric acid metabolism, contributing to gout and related chronic diseases. When traditional drugs are used to treat hyperuricemia, side effects are inevitable, which promotes the exploration of new bioactive compounds. Protein hydrolysates and peptides are gradually showing potential in the treatment of hyperuricemia. This study investigated the uric acid inhibitory activity of peptides extracted from Trachurus japonicus using in silico and in vitro methods. We employed in silico virtual enzymolysis and experimental validation to identify bioactive peptides from Trachurus japonicus proteins. Four peptides (DF, AGF, QPSF, and AGDDAPR) were comprehensively screened by molecular docking and database analysis. After solid-phase synthesis, the inhibitory effects of these peptides on hyperuricemia were further verified in vitro and at the cellular level. The results showed that all four peptides have good hyperuricemia-inhibiting activities. Molecular docking and molecular dynamics revealed that peptides DF and AGDDAPR affect the production of uric acid by binding to the active sites of urate transporter 1 (URAT1), glucose transporter 9 (GLUT9), and xanthine oxidase (XOD), while peptides QPSF and AGF mainly influence the XOD active site, confirming that it is feasible to rapidly screen hyperuricemia-inhibiting peptides by molecular docking.