Dihydromyricetin ameliorates hyperuricemia through inhibiting uric acid reabsorption

Abstract BACKGROUND Hyperuricemia (HUA) is a chronic disease caused by abnormal purine metabolism with high prevalence. Dihydromyricetin (DMY) is a natural flavonoid that is abundant in plants, such as vine tea, grapes and bayberry. DMY has been shown to possess multiple biological properties, but its anti‐HUA effect remains underexplored. In the present study, the regulatory effects of DMY on HUA and its complications and mechanism were investigated. RESULTS DMY (10 and 20 μmol L −1 ) treatment significantly reduced xanthine oxidase (XOD) expression and uric acid (UA) synthesis in normal human liver cell strain cells, and intraperitoneal administration of DMY (100 mg kg −1 ) also significantly reduced serum UA and the expression of hepatic XOD in HUA mice. After DMY treatment for 12 consecutive days, the uricosuric protein, ATP‐binding cassette subfamily G member 2, was upregulated, and reabsorption proteins, including urate transporter 1 and glucose transporter 9, were downregulated, which was consistent with the results of monosodium urate‐induced HUA in human renal tubular epithelial cell line and human colon adenocarcinoma cell line cell models. In addition, DMY significantly ameliorated HUA‐induced renal injury, and foot edema induced by monosodium urate. The nucleotide‐binding oligomerization domain‐like receptor family containing pyrin domain 3 (NLRP3) inflammasome was activated in HUA mice as evidenced by upregulation of NLRP3, caspase‐1, ACS, TNF‐ α and IL‐1 β in the kidney and foot, which was significantly suppressed by DMY treatment. CONCLUSION Collectively, these findings suggested that DMY may play important roles in experimental HUA. © 2025 Society of Chemical Industry.