The mature stem of green Asparagus as a potential dietary supplement for hyperuricemia: Asparagus ameliorates hyperuricemia by regulating hepatic uric acid metabolism and renal uric acid excretion

Hyperuricemia (HUA) is a prevalent metabolic disorder and a major risk factor for gout and related complications, necessitating safe and effective management strategies. To this end, this study aimed to identify the most active part of asparagus, as a potent anti-HUA dietary supplement candidate and validate its efficacy and mechanism of action. LC-MS analysis identified that the Mature Stem of Green Asparagus (MSGA) possessed the richest flavonoid profile among asparagus fractions, with rutin content was 1.37 times higher than in other parts, and even 6.35 times higher. In a Drosophila melanogaster model of adenine-induced HUA, MSGA most effectively improved survival rates and climbing ability. Network pharmacology and molecular docking predicted 5′-nucleotidase ecto (Nt5e) and PDZ domain containing 1 (Pdzk1) as potential key targets for MSGA. Subsequent validation in in an adenine-induced HUA mouse model confirmed that MSGA treatment (3 g/kg/d) significantly alleviated HUA, reducing serum uric acid (UA) levels by 47 % and enhancing urinary UA excretion on day 14. Integrated analyses suggested that the benefits of MSGA may involve suppressing hepatic Nt5e activity to reduce UA biosynthesis, and downregulated renal Pdzk1 expression to rebalance urate transporters, thereby promoting renal excretion. In conclusion, this study provides evidence supporting the anti-HUAeffect of MSGA and proposes mechanistic hypothesis centered on dual targets, inferred from integrated analyses. This work highlights the potential of repurposing MSGA, an abundant agricultural byproduct, which represents a promising candidate for the development of sustainable dietary interventions against HUA. • LC-MS and Drosophila assays identified MSGA as the top anti-HUA asparagus part. • Dual targets Nt5e & Pdzk1 explain MSGA's HUA action via hepatic/renal pathways. • Mouse tests confirmed MSGA's efficacy, completing the screening-to-validation chain. • Supports MSGA as a natural HUA supplement while utilizing asparagus byproducts.