Effect and Mechanism of Rhein‐Neodymium Complex on Intestinal Uric Acid Excretion in Rats with Renal Injury and Hyperuricemia

ABSTRACT This study successfully synthesized a well‐defined Rh‐Nd complex and systematically evaluated its urate‐lowering and renal protective effects in a rat model of hyperuricemia with renal injury. The results demonstrated that Rh‐Nd complex not only significantly reduced serum uric acid levels and improved renal function indicators but also exhibited superior activity compared to rhein alone, demonstrating a synergistic enhancement of rhein's efficacy by the rare‐earth element neodymium. Mechanistic studies revealed that Rh‐Nd complex markedly promoted intestinal uric acid excretion by upregulating ABCG2 protein expression in the jejunum and ileum and downregulating GLUT9 protein expression in the ileum and colon, thereby exerting its extra‐renal uric acid clearance effect. Molecular docking further elucidated the high‐affinity binding mode of Rh‐Nd with ABCG2 and GLUT9. This study provides an important material basis and theoretical foundation for the development of efficient and low‐toxicity intestinal uric acid excretion agents.