Han Qing-Qing, Ren Qi-Dong, Guo Xu, Farag Mohamed A, Zhang Yu-Hong, Zhang Meng-Qi, Chen Ying-Ying, Sun Shu-Tao, Sun Jin-Yue, Li Ning-Yang, Liu Chao
Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, Jinan 250100, China; Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150000, China.
Key Laboratory of Novel Food Resources Processing, Ministry of Agriculture and Rural Affairs/Key Laboratory of Agro-Products Processing Technology of Shandong Province/Institute of Agro-Food Science and Technology, Shandong Academy of Agricultural Sciences, Jinan 250100, China.
J Adv Res. 2025 Mar;69:449-461. doi: 10.1016/j.jare.2024.03.029. Epub 2024 Apr 10.
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 via 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 via 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.
据估计，90%的高尿酸血症病例归因于尿酸（UA）排泄能力不足。负责排泄UA的两个主要器官是肾脏（70%）和肠道（30%）。先前的研究报道，石榴皮素（PU）可以预防肾脏和肠道损伤，这使其成为缓解高尿酸血症的潜在候选物。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。
研究PU改善高尿酸血症的效果及作用机制。
使用高尿酸血症小鼠模型评估PU对高尿酸血症的影响及作用机制。应用表型参数、代谢组学分析和16S rRNA测序来探索PU在肾脏和肠道内改善高尿酸血症的效果及基本作用机制。
给予PU可显著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通过激活高尿酸血症小鼠的MAKP/NF-κB，下调UA重吸收蛋白URAT1和GLUT9的表达，同时上调UA排泄蛋白ABCG2和OAT1的表达。此外，PU减轻了肾脏糖代谢紊乱，这有助于改善肾功能和炎症。同样，PU通过抑制高尿酸血症小鼠肠道中的MAKP/NF-κB激活来增加UA排泄蛋白的表达。此外，PU恢复了高尿酸血症小鼠的肠道微生物群失调。
本研究揭示了PU通过修复高尿酸血症小鼠的肾脏和肠道损伤对高尿酸血症的改善作用，有望开发用作降尿酸剂的营养保健品。
