Euscaphic Acid from Rosa roxburghii Tratt Fruit Ameliorates Ulcerative Colitis by Modulating Oxidative Stress, Inflammation, Gut Microbiota, and Metabolism

Although euscaphic acid (EA)—the main active component of Rosa roxburghii Tratt fruit—possesses potential antioxidant, anti-inflammatory, and intestinal protective effects, the mechanisms underlying these properties remain unclear. This study aimed to investigate whether EA can alleviate dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) through multiple mechanisms such as inhibiting oxidative stress, regulating inflammation, remodeling the gut microbiota, and restoring metabolic disturbances. Using a DSS-induced mouse model of UC and integrating histopathological examination, Western blotting, 16S rRNA sequencing, untargeted metabolomics, transcriptome sequencing, and fecal microbiota transplantation, EA’s mechanisms of action were investigated at multiple levels, including the tissue, microbial, and metabolic levels. EA counteracted DSS-induced alterations in MPO, SOD, MDA, IL-6, IL-1β, and TNF-α. In addition, EA intervention improved UC and reversed the reduction in Bacteroides uniformis (B. uniformis) in UC mice. Further studies confirmed that B. uniformis is a key species mediating the UC-alleviating effects of EA. Metabolomics analysis indicated that EA could mitigate the effects of metabolic disorders; transcriptomic analysis indicated that it inhibits inflammatory signaling pathways; and multi-omics analysis further revealed that it alleviates UC by restoring the gut microbiota and correcting metabolic disorders while simultaneously inhibiting oxidative and pro-inflammatory pathways.