Ampelopsis japonica Extract Exhibited Significant Uric Acid-Lowering Effect by Downregulating URAT1/GLUT9 and Alleviates Inflammation Through TLR4/NF-κB Pathway

Hyperuricemia (HUA) is a metabolic disorder characterized by abnormal purine metabolism within the body. <i>Ampelopsis japonica</i> (Thunb.) Makino has traditionally been utilized in the treatment of various kidney diseases; however, its specific anti-hyperuricemic effects and the underlying mechanisms warrant further investigation. This study investigates the mechanism of action by which <i>A. japonica</i> extract (AJE) addresses HUA using a combination of pharmacology techniques, including network pharmacology and metabolomics. A HUA mouse model was established using potassium oxonate and hypoxanthine. AJE intervention significantly reduced serum uric acid and creatinine levels in HUA mice and markedly decreased glomerular atrophy and renal tubular degeneration. Metabolic profiling revealed distinct metabolic profiles between AJE-intervention and control groups, further demonstrating that AJE corrected disruptions in arginine biosynthesis, purine metabolism, pyrimidine metabolism, and arachidonic acid metabolism. The results of the network pharmacology-based study indicate that AJE can alleviate HUA by modulating the TNF pathway and the Toll-like receptor pathway. The mechanisms of action of AJE in HUA involve the inhibition of xanthine oxidase (XOD) to reduce uric acid synthesis, downregulation of URAT1 and GLUT9 to decrease uric acid reabsorption, and suppression of the TLR4/NF-<i>κ</i>B pathway to mitigate inflammation in the HUA mouse model. Therefore, AJE demonstrates significant potential as a therapeutic intervention for HUA and its associated renal complications.