Identification of the polyphenols from Lonicera flos-Lonicera Caulis compatibility in gut content and their implication in ameliorating gouty arthritis

The combination of Lonicerae flos and Lonicerae Caulis, a traditional medicinal pair, is commonly used in folk medicine for the treatment of inflammatory conditions such as gouty arthritis (GA). However, their combined Polyphenols (FP-CP) against GA have not yet been explored, the specific components responsible for its efficacy remain to be identified. This study unveils the protective mechanism of FP-CP against inflammatory resorption by regulating gut microbiota and metabolites in GA rat. Using a GA rat model and UPLC-MS/MS metabolomic analysis of intestinal contents, we identified seven primary prototype absorption components of FP-CP, including Flavonoids luteolin, chrysoeriol, sakuranetin, and eriodictyol, alongside the phenolic acids caffeic acid, caffeoyl quinic acid, and desaminotyrosine. This suggests that FP-CP may exert its effects in association with modulation of the intestinal microbiota. Concurrent 16S rRNA gene Sequencing revealed that FP-CP intervention significantly modulated the gut microbiota, increasing the abundance of beneficial genera such as Alloprevotella, Akkermansia, and Bifidobacterium. Correlation analysis indicated a strong positive association between these components and the ameliorated microbial and metabolic profiles. Furthermore, network pharmacology and molecular docking predicted that the key Flavonoids (luteolin, chrysoeriol, sakuranetin) could interact with core targets in the PI3K-Akt and MAPK signaling pathways, which was preliminarily validated by the downregulation of related mRNA and protein in synovial tissue. Our findings provide direct chemical evidence for these components, particularly the Flavonoids, are the crucial pharmacodynamic basis for FP-CP anti-GA effects, likely acting through modulation of the gut microbiota-host metabolism axis.