Comparative analysis of Andrias davidianus bone-derived peptides from distinct habitats and their antihyperuricemic activity

Andrias davidianus bone peptides (ADBP), known for their potent xanthine oxidase (XOD) inhibitory activity, show promise as adjunctive agents for the treatment of hyperuricemia (HUA). However, their quality control and antihyperuricemic efficacy across different farming regions have not been thoroughly investigated. This study undertook a comparative analysis of ADBP from nine representative farming locations, developed a high-performance liquid chromatography (HPLC) fingerprint, and evaluated the antihyperuricemic activity of the most promising sample both in vitro and in vivo. The nine ADBP samples predominantly consisted of low-molecular-weight peptides with high protein content. However, their mineral and amino acid profiles exhibited significant variability, which served as key distinguishing markers. A reliable HPLC fingerprint was established to characterize ADBP from the different farming regions. Based on compositional analysis and XOD inhibitory activity, the ADBP obtained from the Hunan Zhangjiajie (HNZJJ) region was selected for further investigation. In vitro experiments utilizing an optimized adenosine-induced HUA model in LO₂ cells confirmed the uric acid-lowering effect of the selected ADBP. In vivo experiments using a mouse model demonstrated that ADBP significantly suppressed hepatic uric acid synthesis by inhibiting adenylate deaminase (ADA), XOD activity, and reducing serum uric acid levels. Additionally, ADBP alleviated HUA-induced liver damage by enhancing hepatic antioxidant defenses. Metabolomic analysis revealed that ADBP-induced alterations in liver metabolites may contribute to the alleviation of HUA. These metabolites were notably enriched in pathways related to linoleic acid metabolism, arginine and proline metabolism, caffeine metabolism, cysteine and methionine metabolism, and purine metabolism. These findings underscore the potential of ADBP as a functional ingredient for food and biomedical applications aimed at the prevention and adjunctive treatment of HUA.