Urolithin C Ameliorates Hyperuricemia by Mitigating Renal Dysfunction through ROS-p38/ERK MAPK Axis Suppression

IF 6.2 1区农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY

Journal of Agricultural and Food Chemistry Pub Date : 2025-09-01 DOI:10.1021/acs.jafc.5c09146

Qingqing Han, Nan Chen, Kun Peng, Muxuan Wang, Mo Chen, Nilufar Z. Mamadalieva, Yuhong Zhang*, Chao Liu* and Qidong Ren*,

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Abstract

Hyperuricemia (HUA) is a prevalent metabolic disorder, with limited therapeutic options. This study investigated the effects and mechanisms of urolithin C (UroC), a gut-microbiota-derived bioactive metabolite from ellagitannin-rich foods, in the management of HUA. In HUA mice, UroC significantly reduced serum uric acid (SUA) levels, outperforming its analogs, UroA and UroB. UFLC-MS/MS identified free UroC as the primary active form in vivo. Mechanistically, UroC alleviated HUA by enhancing renal UA excretion, while concurrently ameliorating renal oxidative stress and fibrosis. Moreover, UroC inhibited UA-induced p38/ERK MAPK activation by reducing the level of reactive oxygen species (ROS) production. Rescue experiments further confirmed that UroC improved the expression of renal UA transporters and fibrosis markers via p38/ERK MAPK inhibition. These findings highlight UroC as a promising food-derived candidate for HUA management, promoting renal protection and enhancing UA excretion via the ROS-p38/ERK MAPK axis.

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尿素C通过抑制ROS-p38/ERK MAPK轴减轻肾功能障碍改善高尿酸血症

高尿酸血症（HUA）是一种普遍的代谢性疾病，治疗选择有限。本研究探讨了尿素C （UroC）在HUA管理中的作用和机制，尿素C是一种肠道微生物来源的生物活性代谢物，来自富含鞣花单宁的食物。在HUA小鼠中，UroC显著降低血清尿酸（SUA）水平，优于其类似物UroA和UroB。UFLC-MS/MS鉴定游离尿c为体内主要活性形式。从机制上讲，尿c通过增强肾脏UA排泄来减轻HUA，同时改善肾脏氧化应激和纤维化。此外，尿c通过降低活性氧（ROS）的产生水平来抑制ua诱导的p38/ERK MAPK的激活。救援实验进一步证实，尿路c通过抑制p38/ERK MAPK改善肾脏UA转运蛋白和纤维化标志物的表达。这些发现强调了尿c作为一种有希望的食物来源的HUA管理候选物，通过ROS-p38/ERK MAPK轴促进肾脏保护和增强UA排泄。

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来源期刊

Journal of Agricultural and Food Chemistry 农林科学-农业综合

CiteScore

9.90

自引率

8.20%

发文量

1375

审稿时长

2.3 months

期刊介绍： The Journal of Agricultural and Food Chemistry publishes high-quality, cutting edge original research representing complete studies and research advances dealing with the chemistry and biochemistry of agriculture and food. The Journal also encourages papers with chemistry and/or biochemistry as a major component combined with biological/sensory/nutritional/toxicological evaluation related to agriculture and/or food.