Pithecellobium clypearia ameliorates ulcerative colitis through regulation of purine metabolism and gut microbiota

Background Pithecellobium clypearia (PC) is a traditional Chinese medicine with anti-inflammatory effects. However, the preventive efficacy and underlying mechanisms of PC in ulcerative colitis (UC) remain unclear. Objective This study applied an integrated microbiome-metabolomic approach to investigate PC’s pharmacological mechanisms against UC. Materials and methods A dextran sulfate sodium (DSS)-induced UC model was established, and the preventive efficacy of PC was evaluated using the disease activity index (DAI), histopathology, inflammatory cytokines, and tight junction proteins. Subsequently, 16S rRNA sequencing and metabolomics were performed to analyze alterations in the gut microbiota composition and colonic metabolic profiles. Results PC significantly ameliorated DSS-induced weight loss, reduced DAI scores, prevented colon shortening, and alleviated mucosal damage. Furthermore, PC decreased pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), increased anti-inflammatory IL-10, and restored tight junction expression. The 16S rRNA sequencing showed PC restored gut dysbiosis, enriching beneficial Bacteroides while reducing pathogenic Escherichia-Shigella. Metabolomics indicated PC modulated colonic purine metabolism, normalizing key metabolites like xanthylic acid and aminoimidazole ribotide. Correlation analysis confirmed a strong crosstalk between these purine metabolites and specific gut microbiota. Discussion and conclusions PC ameliorates UC by suppressing inflammation and protecting the intestinal barrier. Its preventive mechanisms may be associated with the regulation of gut microbiota and host purine metabolism, providing a theoretical basis for future clinical applications.