Polygonatum sibiricum Delar. ex Redoute: A Potential Functional Food for the Prevention and Treatment of Hyperuricemia

This study evaluated the antihyperuricemic potential of Polygonatum sibiricum (HJ) in both animal and human models. A mouse hyperuricemia (HUA) model was established by administering a high uric acid (UA) diet. The model was then treated with HJ water extract. Serum levels of UA, creatinine (Cr), and urea nitrogen (BUN) were measured using biochemical assay kits. Kidney tissue damage was assessed through H&E and PAS staining. Network pharmacology analysis was employed to elucidate potential mechanisms of action. Untargeted metabolomics analysis was performed on mouse serum using liquid chromatography‐mass spectrometry. HJ water extract significantly reduced serum UA levels in HUA mice from 700.82 μmol/L to 236.61 μmol/L (66% decrease). The treatment also markedly lowered serum creatinine and BUN levels, inhibited xanthine oxidase activity, and alleviated renal and glomerular histopathology. Network pharmacology identified MAOA and CYP3A4 among key targets, implicating regulation of histidine metabolism and steroid hormone biosynthesis. Untargeted metabolomics further revealed HJ‐induced alterations in tyrosine metabolism, amino acid biosynthesis, and histidine pathways. Western blotting confirmed downregulation of MAOA and CYP1A1 proteins. These findings suggest dual mechanisms of action: MAOA‐mediated modulation of histidine metabolism and CYP enzyme‐mediated adjustment of steroid hormone synthesis. In a pilot clinical study, 30 HUA volunteers consuming 0.2 g HJ daily for 8 weeks showed a progressive reduction in serum UA by approximately 22% without adverse effects. These results support the development of HJ as a functional food ingredient for the prevention and treatment of HUA. Further research is warranted to fully elucidate the mechanisms of action and optimize dosing regimens for clinical application.