Multi-omics analysis reveals the mechanism of verbenalin in treating gout via modulating purine metabolism, gut microbiota, and inflammatory pathways

Background: Gout is a prevalent metabolic disorder characterized by hyperuricemia and inflammation. Verbenalin, an iridoid glycoside from Verbena officinalis, possesses anti-inflammatory properties; however, its therapeutic potential and underlying mechanisms in gout remain underexplored. Objective: This study aimed to evaluate the pharmacological effects and elucidate the molecular mechanisms of verbenalin in a rat model of gout. Methods: Hyperuricemia and acute gouty arthritis were induced in rats using potassium oxonate/hypoxanthine and monosodium urate, respectively. Verbenalin was administered orally for 7 days. Therapeutic efficacy was assessed via physical symptom scores (inflammation, gait, swelling), renal/hepatic function indices, and histopathology. Furthermore, a multi-omics strategy integrating transcriptomics, metagenomics, and metabolomics, combined with Western blotting, was employed to investigate the pharmacological mechanisms. Results: Verbenalin treatment significantly alleviated joint inflammation and swelling while improving gait scores. It effectively lowered serum uric acid (UA), creatinine, and BUN levels, inhibited hepatic xanthine oxidase (XOD) activity, and promoted urinary UA excretion. Histopathological damage in the joints, kidneys, and liver was markedly mitigated. Mechanistically, verbenalin downregulated the expression of urate transporters (URAT1, GLUT9) and inflammatory mediators (NLRP3, IL-1β) by inhibiting the PI3K-AKT and MAPK signaling pathways. Multi-omics analysis further revealed that verbenalin restored gut microbiota diversity and modulated purine metabolism, correlating with reduced UA levels. Conclusion: These findings demonstrate that verbenalin may exert anti-gout effects through the potential synergy of modulating purine metabolism, shifting gut microbiota composition, and suppressing PI3K-AKT and MAPK inflammatory signaling pathways. This study provides a preliminary scientific basis for further investigation into verbenalin as a prospective multi-target therapeutic candidate.