Abstract
Hyperuricemia, characterized by elevated serum uric acid levels, is a major risk factor for gout and kidney disease. This study evaluated the antihyperuricemic effects of Cornus officinalis extract (COE) using urate transporter 1 (URAT1)-expressing oocytes and a hyperuricemia rat model. COE effectively inhibited uric acid absorption by modulating URAT1, with an IC(50) value of 3.24 µg/mL. In the hyperuricemia model, COE administration (100 and 200 mg/kg) significantly reduced serum uric acid levels and increased urinary uric acid excretion. The primary constituents of COE, morroniside (MO) and loganin (LO) exerted similar effects, with MO exhibiting potent inhibition of uric acid absorption even at low concentrations. Kidney tissue analysis revealed a reduction in blood urea nitrogen (BUN) levels, indicating improved renal function. Liver function parameters (ALT, AST, and LDH) remained unchanged, suggesting an absence of hepatotoxicity. Ultra-high-performance liquid chromatography with charged aerosol detection (UHPLC-CAD) analysis identified MO (17.8 mg/g), LO (9.8 mg/g), and cornin (1.4 mg/g) as the principal components of COE. These findings suggest that COE enhances uric acid excretion via URAT1 regulation and exerts renoprotective effects, highlighting its potential as an antihyperuricemic agent. Furthermore, MO and LO were identified as the primary active constituents, and COE appears to be a promising therapeutic candidate with a favorable safety profile.