Stachydrine from Natural Foods Alleviates Hyperuricemia by Modulating Renal Urate Transporters and Suppressing Mitochondrial Oxidative Stress.

Hyperuricemia (HUA) is a metabolic disease caused by disrupted purine metabolism, characterized by abnormally elevated uric acid (UA) levels. Stachydrine, an alkaloid in natural foods, exhibits multiple biological activities. This study aimed to evaluate the effects of stachydrine on alleviating HUA. An HUA mouse model was established through high-nucleoside diet induction, and stachydrine's effects on UA levels and renal injury were investigated. Our findings revealed that stachydrine enhanced uric acid excretion by upregulating ATP-binding cassette subfamily G member 2 (ABCG2). Furthermore, stachydrine mitigated HUA-induced renal inflammation, mitochondrial oxidative stress and apoptosis. Mechanistically, stachydrine facilitated the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) by downregulating Kelch-like ECH-associated protein 1 (Keap1), subsequently activating the Keap1/Nrf2 signaling pathway and alleviating local oxidative stress. This study demonstrated the UA-lowering and renoprotective effects of stachydrine, suggesting its potential as a functional food ingredient for mitigating HUA.