高尿酸血症是一种慢性疾病，其特征是尿酸水平持续升高，通常导致痛风性关节炎和肾功能不全。茯苓是一种传统中药材，具有显着的利尿和抗炎特性，广泛用于治疗水肿、炎症、病毒感染和肿瘤。最近的研究表明，茯苓具有降低尿酸水平和减轻肾脏损伤的潜力，使其成为高尿酸血症治疗的有希望的候选者。但其药理机制还需要进一步探索。本研究旨在利用代谢组学和网络药理学方法阐明茯苓缓解高尿酸血症的机制。通过高酵母饮食联合氧酸钾诱导大鼠高尿酸血症。通过测量血清尿酸、肌酐、尿素氮水平、肝黄嘌呤氧化酶活性和肾组织形态来评估茯苓的作用。采用非靶向代谢组学来鉴定差异代谢物并探索其治疗效果所涉及的代谢途径。利用网络药理学分析潜在靶点和信号通路，并通过分子对接和ELISA分析进行验证。茯苓提取物显着降低血清尿酸、肌酐和尿素氮水平，抑制黄嘌呤氧化酶活性，减轻肾脏损伤。代谢组学与网络药理学相结合，确定黄嘌呤脱氢酶和脂肪酸合酶为关键靶点，而嘌呤代谢、脂肪酸生物合成和初级胆汁酸生物合成被确定为关键途径。 ELISA证实茯苓抑制高尿酸血症大鼠中黄嘌呤脱氢酶和脂肪酸合成酶的表达。分子对接进一步验证了核心化合物与关键靶点之间的强结合相互作用。茯苓通过调节多个化合物、靶点和通路来缓解高尿酸血症。通过网络药理学和代谢组学揭示茯苓选择性调节黄嘌呤脱氢酶和脂肪酸合酶，影响嘌呤代谢、脂肪酸生物合成和初级胆汁酸生物合成途径。这些发现为其治疗机制提供了深入的见解，支持茯苓在治疗与高尿酸血症相关的代谢紊乱和肾脏损伤方面的临床应用。版权所有 © 2024。由 Elsevier B.V. 出版。

Hyperuricemia is a chronic condition characterized by persistently elevated uric acid levels, often leading to gouty arthritis and renal insufficiency. Poria cocos F.A.Wolf, a traditional Chinese medicinal herb, possesses notable diuretic and anti-inflammatory properties and is widely used to treat edema, inflammation, viral infections, and tumors. Recent studies suggest that Poria cocos has the potential to lower uric acid levels and mitigate kidney damage, making it a promising candidate for hyperuricemia treatment. However, its pharmacological mechanisms require further exploration.This study aims to elucidate the mechanisms by which Poria cocos alleviates hyperuricemia, using metabolomics and network pharmacology approaches.Hyperuricemia was induced in rats via a high-yeast diet combined with potassium oxonate. The effects of Poria cocos were assessed by measuring serum uric acid, creatinine, urea nitrogen levels, hepatic xanthine oxidase activity, and renal tissue morphology. Non-targeted metabolomics was employed to identify differential metabolites and explore the metabolic pathways involved in its therapeutic effects. Network pharmacology was utilized to analyze potential targets and signaling pathways, which were validated through molecular docking and ELISA analysis.Poria cocos extract significantly reduced serum uric acid, creatinine, and urea nitrogen levels, inhibited xanthine oxidase activity, and attenuated kidney damage. Metabolomics combined with network pharmacology identified xanthine dehydrogenase and fatty acid synthase as key targets, while purine metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis were identified as critical pathways. ELISA confirmed that Poria cocos suppressed xanthine dehydrogenase and fatty acid synthase expression in hyperuricemic rats. Molecular docking further verified strong binding interactions between core compounds and key targets.Poria cocos alleviates hyperuricemia by modulating multiple compounds, targets, and pathways. Through network pharmacology and metabolomics, it reveals that Poria cocos selectively regulates xanthine dehydrogenase and fatty acid synthase, influencing purine metabolism, fatty acid biosynthesis, and primary bile acid biosynthesis pathways. These findings provide insights into its therapeutic mechanisms, supporting the clinical application of Poria cocos in treating metabolic disorders and kidney damage associated with hyperuricemia.Copyright © 2024. Published by Elsevier B.V.