Structural characterization of a novel low-molecular-weight β-fructan from Panax quinquefolius and its effect on ameliorating hyperuricemia

ABSTRACT: Background Hyperuricemia (HUA), a widespread metabolic disorder, is closely associated with renal injury, tubulointerstitial fibrosis, and uric acid nephrolithiasis, posing a significant global health burden. In this study, we investigated the anti-hyperuricemic effects and underlying mechanisms of a novel low-molecular-weight β-fructan (AGP-W) derived from Panax quinquefolius L. Methods AGP-W was extracted from P. quinquefolius using ultra-high pressure extraction. Its structural characteristics were determined by molecular weight analysis, monosaccharide composition, and glycosidic linkage assays. Its therapeutic effects were evaluated in hyperuricemic mice by assessing serum parameters, renal transporters, intestinal barrier integrity, and gut microbiota. Results AGP-W was characterized as a novel low-molecular-weight β-fructan. AGP-W administration significantly and dose-dependently reduced serum uric acid, creatinine, and blood urea nitrogen levels (P < 0.01), while ameliorating lipid metabolic disorders against the hyperuricemic mouse model. Mechanistically, AGP-W restored the expression of renal urate exporters ABCG2, OAT1/3, and OCT and suppressed the expression of URAT1, GLUT9. As for its effects on the intestines, it restored intestinal barrier integrity by upregulating tight junction proteins of ZO-1, Occludin, Claudin-1, reduced villus atrophy, and modulated gut microbiota by enriching Lactobacillus and suppressing HUA-associated bacteria. Conclusion AGP-W exerts potent anti-hyperuricemic effects by modulating renal urate transporters, and restoring intestinal barrier function with gut microbiota regulation. These findings highlight AGP-W as a promising natural candidate for hyperuricemia treatment.