Combination of Withania coagulans and Fagonia cretica ameliorates hyperuricemia by re-modulating gut microbiota-derived spermidine and traumatic acid

This study highlights the complementary mechanisms of Withania coagulans (WC) and Fagonia cretica (FC) in managing hyperuricemia (HU). WC primarily inhibits xanthine oxidase (XOD), reducing uric acid (UA) synthesis, while FC enhances UA excretion by upregulating transporters ABCG2 and SLC2A9. The WC extract alleviated PO+A-induced HU through its anti-inflammatory properties and modulation of gut microbiota-derived SP production, leading to XOD inhibition by suppressing the TNF signaling pathway. Similarly, the FC extract exhibited anti-inflammatory effects and modulated TA production, promoting UA exporters (Abcg2/Slc2a9) and enhancing intestinal UA excretion by suppressing the IL-17 signaling pathway. The combination of WC and FC synergistically reduces UA levels by both inhibiting XOD and promoting UA excretion. These results support the potential of WC and FC as natural therapeutic agents for HU management.