Galangin Protects against Hyperuricemia via Ameliorating Gut–Kidney Axis Dysfunction in Mice

Hyperuricemia (HUA) is often associated with renal injury and intestinal flora disturbance. Galangin, a polyphenolic compound found in <i>Alpinia officinarum</i> and propolis, has demonstrated the capacity to inhibit xanthine oxidase (XO) activity both <i>in vitro</i> and <i>in silico</i>; however, the precise mechanisms underlying its effects <i>in vivo</i> remain unclear. This study aims to investigate the effect of galangin on uric acid (UA) metabolism as a prospective strategy for lowering UA and further explore the underlying mechanisms. Galangin mitigates kidney tissue injury and fibrosis, reduces the serum UA level via inhibiting UA synthesis in the liver, and promotes UA excretion in the kidney. Molecular docking results also uncovered the structure-activity relationship of galangin and the UA transporters GLUT9, URAT1, ABCG2, and OAT1, implying a potential interaction. Also, galangin mitigated the HUA-activated NF-κB/MAPK signaling pathway in the kidney, as well as colon tissue damage and barrier dysfunction, which are closely linked to deteriorated intestinal permeability. Moreover, galangin remedied the alterations in intestinal microecology caused by HUA, encompassing changes in the structure and composition of gut microbial species as well as the metabolism of SCFAs. Collectively, this study demonstrates that galangin exerted an improvement on HUA by ameliorating gut-kidney axis dysfunction.