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.

Sulfometuron-methyl (SM), as a sulfonylurea herbicide, is widely used in agricultural production. In recent years, it has also been employed in the control and management of Spartina alterniflora in some coastal areas of China. Its potential risks to aquatic ecosystems have drawn increasing attention. However, the current data on the systematic toxicity assessment of SM in model organisms is still very limited. This study used zebrafish (Danio rerio) as an in vivo model to systematically evaluate the toxic effects of SM on early embryonic development and focused on the mediating mechanism of the Wnt/β-catenin signaling pathway in it. Zebrafish embryos were exposed to different concentrations (10, 20, 40 mg/L) of SM starting from 1.75 hpf until 72 hpf. The results showed that SM significantly increased the embryo mortality rate, decreased the hatching rate, and induced developmental malformations such as shortened body length and yolk sac edema in a concentration-dependent manner. At the mechanism level, SM exposure significantly reduced the number of H3P-positive mitotic active cells in the embryos, suggesting that fewer cells entered mitosis; meanwhile, the activities of superoxide dismutase (SOD) and catalase (CAT) showed compensatory changes, indicating that oxidative stress was induced in the embryos, which may contribute to subsequent cellular damage. qRT-PCR analysis further revealed that SM exposure downregulated the transcriptional levels of cell cycle-related genes (CyclinD1, CDK4, CDK6), while upregulating the expression of apoptosis-related genes (p53, bax, caspase-9, caspase-3), suggesting that cell cycle arrest and the dysregulation of the endogenous apoptotic pathway were activated. Additionally, SM exposure could dysregulate the Wnt/β-catenin signaling pathway, specifically manifested as significant upregulation of target genes C-myc and Ctnnb2, and significant downregulation of the negative regulatory factor Axin2. Using the Wnt/β-catenin pathway-specific inhibitor IWR-1 for intervention could partially reverse the embryonic developmental retardation phenotypes induced by SM, providing additional evidence for the mediating role of this pathway in the developmental toxicity of SM. In summary, this study systematically elucidates the multi-level molecular mechanism by which SM induces oxidative stress and cell apoptosis through the abnormal dysregulation of the Wnt/β-catenin signaling pathway, reduced mitotic activity, and ultimately drives the toxicity of zebrafish embryo development. This provides new experimental evidence and a theoretical basis for the aquatic ecological risk assessment of SM.