Structural characterization of a jujube polysaccharide and its regulation of the gut-kidney axis to alleviate hyperuricemia and renal injury in mice.

Hyperuricemia (HUA) is a chronic metabolic disorder arising from purine metabolism dysfunction, characterized by abnormally elevated serum uric acid (UA) levels and closely associated with renal injury. In this study, we preliminarily investigated the ameliorative effects and potential mechanisms of a polysaccharide, JP, derived from jujube (Ziziphus jujuba Mill.) on HUA. Our results showed that JP is an acidic polysaccharide with a molecular weight of approximately 1.5 × 105 Da, primarily composed of arabinose, glucose, and xylose. Daily administration of JP (50, 100, 200 mg/kg) dose-dependently reduced serum UA levels and attenuated renal injury in hyperuricemic model mice. Mechanistically, JP suppressed UA production by inhibiting renal xanthine oxidase activity, while concurrently promoting UA excretion via downregulating the expression of renal urate reabsorption transporters URAT1 and GLUT9. Furthermore, JP ameliorated renal injury through inhibiting the renal TLR4/NF-κB signaling pathway, reducing TNF-α levels, and alleviating oxidative stress and fibrosis. In addition, JP remodeled the disturbed gut microbiota, significantly enriching beneficial genera such as Akkermansia and Dubosiella. Collectively, JP exerts multifaceted ameliorative effects on HUA by modulating renal urate metabolism and inflammatory responses, as well as reshaping gut microbiota homeostasis. These findings provide preliminary experimental evidence for JP as a dietary intervention strategy targeting the gut-kidney axis to improve HUA and associated renal injury.