Phragmites Communis (Lu Gen) Alleviates Hyperuricemia via Xanthine Oxidase Inhibition and Gut-Microbiota-Mediated Metabolite Urate Transporter Regulation

Background: Hyperuricemia (HU) results from excessive uric acid (UA) production/impaired excretion and is associated with gout and renal dysfunction. Gut microbiota dysbiosis may impair intestinal UA excretion, disrupt the gut barrier, and promote inflammation. Traditional Chinese medicine (TCM), with multitarget and microbiota-modulating effects, may offer a therapeutic strategy for HU. In this study, the rhizome of Phragmites communis, a TCM used for clearing heat and promoting diuresis, was investigated. Specifically, we evaluated whether P. communis could alleviate HU by suppressing xanthine oxidase (XOD) and modulating urate transporter expression, thereby reducing UA production while promoting its excretion. Method: The effects of a crude extract of P. communis were investigated with in vitro and in vivo models using molecular, 16S rRNA sequencing, and metabolomic analyses. Results: P. communis significantly decreased serum uric acid (SUA) levels by inhibiting XOD and improving renal and intestinal urate excretion, accompanied by decreased renal and increased intestinal solute carrier family 2 member 9 (SLC2A9) and enhanced ATP-binding cassette subfamily G member 2 (ABCG2) expression, restored gut barrier integrity, and suppressed inflammation. Microbiota analysis revealed enrichment of Ligilactobacillus, Prevotella, and Dubosiella. Fecal metabolomics identified hippuric acid (HA), which correlated with Ligilactobacillus abundance. In vitro, HA enhanced ABCG2, PDZ domain-containing 1 (PDZK1), and SLC2A9 expression. Molecular docking identified feruloylquinic acid (FAQ) as the favorable XOD inhibitor. Conclusions: P. communis exerts anti-hyperuricemic effects by inhibiting UA biosynthesis, promoting UA excretion, modulating gut microbiota, restoring gut barrier integrity, and suppressing inflammation, highlighting its potential as a TCM-based therapeutic intervention for HU.