Tissue-specific metabolism of Naringin and its modulation of the UA metabolism and gut microbiota in hyperuricemia mice.

Abstract

Hyperuricemia (HUA) is a metabolic disorder caused by purine metabolism dysfunction or impaired uric acid excretion. With the change of lifestyle, the incidence of HUA has been increasing annually. Naringin (NAR) is a natural dietary flavonoid compound with extensive biological activities. However, its potential ameliorative effects on HUA and the underlying mechanisms remain to be explored. This study aims to investigate the mechanism of action of NAR on HUA through the perspectives of NAR metabolism and gut microbiota. A mouse model of HUA was induced by a combination of potassium oxonate and a high-purine diet. We found that NAR ameliorated the symptoms of HUA by modulating uric acid metabolism. UHPLC-Q-Orbitrap-MS/MS was employed to analyze NAR metabolites in seven tissues. A total of 23 naringin-related metabolites were identified, including 5 Phase I and 18 Phase II metabolites. NAR was distributed in all eight detected tissues. After in vivo phase I and phase II metabolism, the existence forms of its metabolites varied among different tissues. Meanwhile, NAR could regulate the composition of gut microbiota and increase the abundances of beneficial bacteria such as norank_f__Muribaculaceae, Lactobacillus, Alloprevotella and Prevotellaceae_UCG-001. In conclusion, this study supports the indicative role of NAR in alleviating HUA and provides insights for the subsequent research and development of naringin derivatives with enhanced bioactivity.