Punicalagin attenuates hyperuricemia via restoring hyperuricemia-induced renal and intestinal dysfunctions

作者：Qingqing Han, Qi‐dong Ren, Xu Guo, Mohamed A. Farag, Yuhong Zhang, Meng-qi Zhang, Yingying Chen, Shutao Sun, Jinyue Sun, Ningyang Li, Chao Liu · 发表于：Journal of Advanced Research · 年份：2024 · DOI：10.1016/j.jare.2024.03.029 · 被引用次数：70 · 研究领域：Pomegranate: compositions and health benefits、Gout, Hyperuricemia, Uric Acid、Cynara cardunculus studies

INTRODUCTION: 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. OBJECTIVE: To investigate the effect and action mechanisms of PU for ameliorating hyperuricemia. METHODS: 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. RESULTS: 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 prot...