It is estimated that 90% of hyperuricemia cases are attributed to the inability to excrete uric acid (UA). The two main organs in charge of excreting UA are the kidney (70%) and intestine (30%). Previous studies have reported that punicalagin (PU) could protect against kidney and intestinal damages, which makes it a potential candidate for alleviating hyperuricemia. However, the effects and deeper action mechanisms of PU for managing hyperuricemia are still unknown. To investigate the effect and action mechanisms of PU for ameliorating hyperuricemia. The effects and action mechanisms of PU on hyperuricemia were assessed using a hyperuricemia mice model. Phenotypic parameters, metabolomics analysis, and 16S rRNA sequencing were applied to explore the effect and fundamental action mechanisms inside the kidney and intestine of PU for improving hyperuricemia. PU administration significantly decreased elevated serum uric acid (SUA) levels in hyperuricemia mice, and effectively alleviated the kidney and intestinal damage caused by hyperuricemia. In the kidney, PU down-regulated the expression of UA resorption protein URAT1 and GLUT9, while up-regulating the expression of UA excretion protein ABCG2 and OAT1 as mediated the activation of MAKP/NF-κB in hyperuricemia mice. Additionally, PU attenuated renal glycometabolism disorder, which contributed to improving kidney dysfunction and inflammation. Similarly, PU increased UA excretion protein expression inhibiting MAKP/NF-κB activation in the intestine of hyperuricemia mice. Furthermore, PU restored gut microbiota dysbiosis in hyperuricemia mice. This research revealed the ameliorating impacts of PU on hyperuricemia by restoring kidney and intestine damage in hyperuricemia mice, and to be considered for the development of nutraceuticals used as UA-lowering agent.

中文翻译：

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安石榴苷通过恢复高尿酸血症引起的肾和肠道功能障碍来减轻高尿酸血症

据估计，90%的高尿酸血症病例是由于尿酸（UA）无法排泄造成的。负责排泄UA的两个主要器官是肾脏（70%）和肠道（30%）。此前的研究表明，安石榴苷 (PU) 可以防止肾脏和肠道损伤，这使其成为缓解高尿酸血症的潜在候选者。然而，PU治疗高尿酸血症的效果和更深层次的作用机制仍不清楚。探讨PU改善高尿酸血症的作用及作用机制。使用高尿酸血症小鼠模型评估 PU 对高尿酸血症的影响和作用机制。应用表型参数、代谢组学分析和16S rRNA测序来探讨PU改善高尿酸血症的肾脏和肠道内的作用和基本作用机制。 PU给药显着降低高尿酸血症小鼠升高的血清尿酸（SUA）水平，并有效减轻高尿酸血症引起的肾脏和肠道损伤。在肾脏中，PU 下调高尿酸血症小鼠体内 UA 吸收蛋白 URAT1 和 GLUT9 的表达，同时上调 UA 排泄蛋白 ABCG2 和 OAT1 的表达，介导 MAKP/NF-κB 的激活。此外，PU 可减轻肾脏糖代谢紊乱，从而有助于改善肾功能障碍和炎症。同样，PU 增加 UA 排泄蛋白表达，抑制高尿酸血症小鼠肠道中 MAKP/NF-κB 的激活。此外，PU 还恢复了高尿酸血症小鼠的肠道微生物群失调。这项研究揭示了 PU 通过恢复高尿酸血症小鼠的肾脏和肠道损伤来改善高尿酸血症的影响，并可考虑开发用作降 UA 剂的营养保健品。