This study investigated the role of exosomes in the pathological processes of gouty arthritis (GA), with the aim of clarifying their mechanistic role and pathological significance in the onset and progression of GA. Using a rat model of GA established through potassium oxonate and yeast gavage combined with intra-articular monosodium urate (MSU) injection, we isolated and characterized plasma exosomes using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. Differential exosomal protein expression was analyzed using 4D label-free proteomics technology, followed by GO and KEGG enrichment analyses, and protein–protein interaction (PPI) network construction to identify core targets. In vivo experiments measured the expression levels of CTSD in synovial tissues and joint fluid, as well as HPRT1 in renal tissues, while in vitro experiments involved co-culturing NRK cells with exosomes to validate target protein expression. The results indicated that serum uric acid levels were significantly elevated in the model group (p < 0.01), accompanied by pronounced joint swelling and inflammation. Exosome characterization confirmed their typical bilayer membrane structure and the expression of marker proteins (CD63/TSG101). Proteomic analysis identified 40 differentially expressed proteins (12 upregulated and 28 downregulated) enriched in pathways such as complement and coagulation cascades, autophagy, lysosomal function, and purine metabolism. In vivo and in vitro experiments demonstrated significantly increased CTSD expression (p < 0.05/p < 0.01) and decreased HPRT1 expression (p < 0.05/p < 0.01) in the model group, suggesting that exosomes are involved in the occurrence and development of GA by regulating purine metabolism and lysosomal dysfunction. These findings offer new insights into disease mechanisms and potential therapeutic targets.

Renal urate deposition is a pathological inflammatory condition characterized by the accumulation of urate crystals in the kidneys, resulting from uric acid supersaturation. Cichorium intybus L. (chicory) is a traditional medicinal herb recognized for its efficacy in treating hyperuricemia and gout; however, its effectiveness and underlying mechanisms in mitigating renal urate deposition remain inadequately understood. This study investigates the role of the ATP-binding cassette sub-family G member 2 (ABCG2) transporter and the lncRNA H19/miR-21-3p in renal urate deposition, while also validating the therapeutic effects and mechanisms of chicory extract. Renal urate deposition was induced in rats through the administration of potassium oxonate, adenine, yeast extract, and lipopolysaccharide. The levels of serum uric acid (SUA), urate deposition, inflammation, renal function, and histological changes were analyzed. Dual-luciferase assays, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and immunohistochemistry were utilized to elucidate the relationship among ABCG2, lncRNA H19, and miR-21-3p. The chemical composition and active ingredients of chicory were analyzed using UPLC-LTQ-Orbitrap-MS, along with molecular docking and cell experiments. In rats with renal urate deposition, serum UA levels were elevated, renal UA excretion was reduced, and levels of low inflammatory factors, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and hypersensitivity C-reactive protein (hs-CRP), were increased. Additionally, significant renal tissue damage accompanied the urate deposition. Notably, these abnormalities were substantially reversed following treatment with chicory extract. A dual-luciferase reporter assay confirmed the regulatory relationships among miR-21-3p, lncRNA H19, and ABCG2. Immunohistochemical analysis and RT-qPCR demonstrated a significant upregulation of miR-21-3p expression, alongside a downregulation of lncRNA H19, ABCG2 mRNA, and ABCG2 expression in the kidney tissue of rats with renal urate deposition. Chicory extract may exert its inhibitory effect on renal urate deposition by regulating the lncRNA H19/miR-21-3p axis to enhance ABCG2 expression. Furthermore, UPLC-LTQ-Orbitrap-MS identified 69 components in the chicory extract, including scopoletin, quercetin-3-O-β-D-glucuronide, 11β,13-dihydrolactucopicrin, and kaempferol-3-O-β-D-glucuronide, which were absorbed into the blood of both normal rats and those with renal urate deposition. Molecular docking and cell experiment further validated the effective regulation of 11β,13-dihydrolactucopicrin in ABCG2 and the lncRNA H19/miR-21-3p axis. The downregulation of ABCG2, mediated by the lncRNA H19/miR-21-3p axis, may represent a critical pathogenic mechanism in renal urate deposition. Chicory alleviates this deposition by modulating the lncRNA H19/miR-21-3p axis to enhance ABCG2 expression, potentially through its component, 11β,13-dihydrolactucopicrin, thereby revealing novel therapeutic insights for renal urate deposition.