Suaeda maritima subsp. Salsa (L.) Soó extract attenuates hyperuricemic renal injury by inhibiting the MAPK/NF-κB/NLRP3 pathway

Abstract Hyperuricemia has become a global metabolic disease, and its progression is closely associated with renal dysfunction and inflammatory injury. Given the limitations of current interventions, it is urgent to discover safe and effective bioactive components from edible natural products. Suaeda maritima subsp. salsa (L.) Soó (JP) is a traditional edible halophyte rich in flavonoids, phenolic acids, and alkaloids. It is considered a plant with health-promoting potential. In this study, we investigated the uric acid-lowering and renoprotective effects of its ethyl acetate extract (JP-EA) and elucidated the underlying mechanisms using network pharmacology, molecular docking, and experimental validation. The results showed that JP-EA significantly reduced serum uric acid levels, improved renal function, and alleviated renal inflammation and fibrosis in hyperuricemic mice. Mechanistically, JP-EA inhibited xanthine oxidase (XOD) activity, downregulated urate reabsorption transporters (URAT1 and GLUT9), upregulated excretion transporters (ABCG2 and OAT1), and suppressed the MAPK/NF-κB/NLRP3 inflammatory pathway, as demonstrated by Western blot and immunofluorescence analyses. ‌Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis identified five key bioactive components, including diosmetin, luteolin, and quercetin, as the major constituents responsible for the observed activities. In conclusion, JP-EA mitigates hyperuricemia and renal inflammatory injury by regulating the MAPK/NF-κB/NLRP3 pathway, supporting its potential application as a functional food ingredient.