Evaluation of the clinical efficacy of Xanthoceras sorbifolium leaves in intervening in hyperuricemia and research on its uric acid-lowering mechanism.

BACKGROUND: Hyperuricemia is a metabolic disorder caused by the malfunction of uric acid metabolism. It is a common risk factor for gout and kidney disease. Currently, first-line pharmacotherapies for hyperuricemia, such as xanthine oxidase inhibitors (e.g., allopurinol and febuxostat) and uricosuric agents (e.g., benzbromarone), effectively lower serum uric acid levels. However, their clinical use is often limited by adverse effects, including hepatorenal toxicity, gastrointestinal disturbances, and hypersensitivity reactions. These limitations highlight the need for safer, better-tolerated therapeutic options. In this context, plant-derived interventions with multi-target mechanisms and favourable safety profiles have gained increasing research interest. Early studies suggest that the leaves of the traditional edible medicine, Xanthoceras sorbifolium Bunge (X. sorbifolium), may be promising for treating HUA. However, their clinical efficacy and mechanism of action remain to be clearly established.

OBJECTIVE: The purpose of the study was to evaluate the clinical effectiveness and safety of X. sorbifolium leaves in managing HUA and to discuss their hypouricemic and organ-protective mechanisms.

METHODS: A randomised controlled trial was conducted involving 120 patients with hyperuricaemia. Of these, 60 patients received tea made from the leaves of X. sorbifolium (n = 60), while the other 60 received febuxostat (n = 60), both for 4 weeks. Safety indicators and serum uric acid levels were measured throughout the trial. Additionally, a proteomic analysis of patient serum was performed alongside network pharmacology screening. In vitro validation was also carried out using injury models in AML12 liver cells and HK-2 renal tubular epithelial cells. The effects of the X. sorbifolium extract (EX) on uric acid metabolism, inflammation, cell apoptosis, and relevant signalling pathways were evaluated using ELISA, Western blot analysis, and flow cytometry.

RESULTS: Clinical trials have shown that patients using X. sorbifolium leaves as a tea substitute and those taking oral febuxostat both effectively decrease their serum uric acid levels, with no statistically significant difference in the rate of reduction. Patients using X. sorbifolium leaves did not experience liver or kidney damage, demonstrating good safety. The PI3K/AKT pathway and inflammatory response were implicated through proteomics and network pharmacology. In vitro, X. sorbifolium and its key active components (quercitrin, rutin, myricitrin) reduced UA production by inhibiting hepatic xanthine oxidase (XOD) activity. They promoted UA excretion by modulating renal urate transporters (upregulating ABCG2/OAT1, downregulating GLUT9/URAT1). X. sorbifolium exerted anti-inflammatory effects on hepatocytes by suppressing the overactivated PI3K/AKT/COX-2 axis and inhibited UA-induced apoptosis in renal cells by activating PI3K/AKT, thereby creating tissue selectivity.

CONCLUSION: X. sorbifolium leaves are an effective and safe natural remedy for HUA. Their mechanism involves multiple actions: reducing UA production, promoting excretion, and protecting organs through bidirectional regulation of the PI3K/AKT pathway. This paper provides scientific evidence for X. sorbifolium as a new approach to treating HUA and its related complications.