Dandelion is an edible and medicinal plant that has beneficial effects in various complex disorders. In this study, we investigated the regulatory effects of dandelion leaf aqueous extract (DAE) on mice with hyperuricemia (HUA) and explored its underlying mechanisms. DAE exhibited a high total phenolic content (363.31 ± 0.61 mg GAC/g) and contained 20 identified polyphenolic compounds. The administration of DAE significantly reduced serum uric acid levels and exerted protective effects on both liver and kidney function in mice with HUA. Mechanistically, DAE inhibited the NLRP3/Caspase-1 and TLR4/MyD88/NF-κB signaling pathways, leading to the downregulated mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), thereby alleviating renal inflammation. Additionally, DAE modulated the gut microbiota composition and increased SCFA-producing bacteria, along with increases in fecal SCFA contents. These findings suggest that DAE effectively mitigates HUA and its associated renal complications by regulating uric acid metabolism, suppressing renal inflammation, and restoring gut microbial homeostasis. Thus, DAE holds promise as a natural adjuvant therapy for HUA and related kidney inflammation.
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