Mechanisms of Arctium lappa root polysaccharides in ameliorating chronic hyperuricemia and renal injury in mice

This study aimed to investigate the therapeutic effects of Arctium lappa root polysaccharides (ALRP) on chronic hyperuricemia (HUA) mice induced by adenine combined with a high-purine diet and to explore the underlying molecular mechanisms. A HUA mouse model was established using this induction approach, and 60 SPF-grade male ICR mice were randomly divided into a normal control group, a model group, a positive control group (febuxostat), a low-dose ALRP group, and a high-dose ALRP group, with intragastric administration for 28 consecutive days. Body weight and renal index were measured, and serum and urinary levels of uric acid (UA) and creatinine (Cre), along with uric acid clearance rate (UACR) and the uric acid-to-creatinine ratio (U/C), were determined. Oxidative stress markers and inflammatory cytokine levels were assessed in renal tissue homogenates, and histopathological changes in kidney tissue were observed by HE staining. Gut microbiota structural changes were analyzed by metagenomic sequencing, and fecal bile acid content was measured by targeted metabolomics. The results showed that, compared with the model group, mice in both ALRP dose groups exhibited significantly increased body weight and significantly reduced renal index; serum UA and Cre levels were significantly decreased, UACR was significantly elevated, and urinary U/C ratio was significantly increased (P<0.05 or P<0.01); renal oxidative stress and inflammatory cytokine levels were significantly reduced (P<0.05 or P<0.01); histopathological scores of kidney tissue were significantly improved, with alleviated renal tubular damage and interstitial inflammation (P<0.05 or P<0.01); gut microbiota α-diversity was increased, β-diversity was significantly altered, the abundance of beneficial bacteria was elevated, and that of harmful bacteria was decreased; and fecal secondary bile acid content was significantly increased (P<0.05 or P<0.01). In conclusion, ALRP exert significant renoprotective effects in chronic HUA mice, and the underlying mechanisms may be related to the reduction of serum uric acid levels, improvement of renal oxidative stress and inflammatory status, modulation of gut microbiota composition, and promotion of bile acid metabolism.