Evodiamine attenuates hyperuricemia-associated gouty arthritis and renal injury through urate-inflammatory axis modulation

Background Therapeutic options for hyperuricemia (HUA) and its complications remain inadequate, particularly when gouty arthritis (GA) and hyperuricemic nephropathy (HN) coexist. Agents with combined urate-lowering, anti-inflammatory, and renoprotective effects are therefore needed. Evodiamine (EVO), a major alkaloid from Evodia rutaecarpa , exhibits anti-inflammatory and analgesic activities, but its role in HUA-related disorders has not been fully defined. Study design and methods We examined the effects of Evodia rutaecarpa water extract (ERWE) and EVO in experimental models of HUA, HN, and GA. Results In the HUA model, ERWE reduced plasma UA levels and increased urinary UA concentration, accompanied by reductions in ALT, AST, and selected inflammatory measurements. Metabolomic profiling indicated that these effects were associated with alterations in pyrimidine metabolism, α-linolenic acid metabolism, and butyrate-related pathways. In the HN model, EVO lowered serum UA and creatinine levels, improved renal pathology, and reduced renal URAT1 and GLUT9 expression. EVO also suppressed NLRP3/caspase-1/IL-1β signaling and reduced the expression of fibrosis-related markers, including α-SMA, COL1A1, and TIMP1. In the GA model, EVO alleviated monosodium urate (MSU)-induced ankle swelling, leukocyte infiltration, and inflammatory mediator production, including IL-1β, TNF-α, and MPO, while inhibiting NLRP3 inflammasome activation. Conclusion ERWE and the alkaloid EVO showed significant protective effects in experimental HUA-related disorders. EVO, in particular, exerted urate-lowering, renoprotective, and anti-inflammatory activities, possibly through regulation of urate transporters and NLRP3 inflammasome signaling.