Walnut peptide reduce uric acid production by non-covalent binding to hypoxanthine in vitro

Hyperuricemia results from abnormal purine metabolism and is frequently associated with a high purine diet. Conventional treatments primarily focus on inhibiting xanthine oxidase (XO) to reduce uric acid production, but these approaches often cause significant side effects and fail to address excessive dietary purine intake. This study investigates a novel strategy utilizing natural dietary peptides that potentially form non-covalent complexes with purines to reduce their absorption, thereby lowering serum uric acid levels. We examined the regulatory effects of walnut-derived peptides, specifically Trp-Asp-Gln-Trp (WDQW), Val-Trp-Pro-Pro (VWPP), and Cys-Phe-Pro-His (CFPH), on hypoxanthine absorption using in vitro RKO cell (Human Colorectal Adenocarcinoma Cells) models and intestinal sac systems. Results demonstrated that CFPH significantly reduced both the production and excretion of uric acid in jejunal tissue (p < 0.05). The WDQW peptide significantly reduced the transport efficiency of hypoxanthine in RKO cells (p < 0.05), demonstrating its potential in regulating purine metabolism. Molecular docking analyses suggested that these peptides may form non-covalent complexes with hypoxanthine, potentially interfering with absorption processes. These findings provide evidence for a potential dietary approach to hyperuricemia management.