Chemical characterization and therapeutic potential of PHB in hyperuricemia based on network pharmacology and animal...

Hyperuricemia (HUA) is a metabolic disease characterized by abnormal purine metabolism. Due to safety and abundant antioxidant content, plant-based beverages are a promising option for managing metabolic disorders. In previous study, we developed a powdered herbal beverage (PHB) containing Polygonatum sibiricum rhizomes, Chaenomeles speciosa (Sweet) Nakai leaves, and Ziziphus jujuba fruit. Thus, this study systematically investigated the anti-HUA effect and underlying mechanisms of PHB through an integrated experimental strategy. The xanthine oxidase inhibitory activity was quantitatively assessed using in vitro enzymatic inhibition assays. UPLC-ESI-QTRAP-MS/MS-based chemical profiling was performed to characterize the bioactive constituents, complemented by network pharmacology analysis to elucidate potential therapeutic targets and critical signaling pathways. Furthermore, the in vivo efficacy and mechanistic basis were rigorously validated in a HUA mouse model. The results showed that PHB exhibited inhibitory activity against xanthine oxidase in vitro. Network pharmacology has revealed that the active components in PHB may alleviate the HUA progression by suppressing inflammatory pathways such as the tumor necrosis factor signaling pathway. In HUA mice, PHB effectively reduced serum uric acid by modulating xanthine oxidase activity and urate transporters, while mitigating hepatic and renal injury. Notably, PHB exerted renal protection through suppressing TNF signaling pathway. Additionally, PHB administration restored gut microbiota diversity and composition. These findings collectively establish PHB as a promising multi-target therapeutic approach for HUA management.