Niclosamide alleviates dextran sulfate sodium-induced colitis in mice by inhibiting S100A4

Objective To investigate the effect and mechanism of niclosamide (Nic), an inhibitor of the calcium-binding protein S100A4, in a mouse model of dextran sulfate sodium (DSS)-induced colitis.Methods A mouse model of colitis was established, and the animals were divided into different intervention groups. Body weight changes, disease activity index (DAI), colon length, and spleen index were recorded. Histopathological changes, as well as the expression of MUC2 and the tight junction protein Occludin in colon tissues, were assessed using hematoxylin-eosin (H&E) staining and immunohistochemistry. The expression of S100A4, myeloperoxidase (MPO), F4/80, and interleukin-1β (IL-1β) in colon tissues was evaluated by immunofluorescence staining.Results Compared with the Ctrl group, the DSS+corn oil group exhibited significant increases in body weight loss, DAI score, colon shortening, and spleen index (p<0.05). Extensive tissue damage, reduced expression of MUC2 and Occludin, and substantial infiltration of MPO⁺ neutrophils and F4/80⁺ macrophages were observed in the colon tissues (p<0.05). In addition, the expression of S100A4 and the pro-inflammatory cytokine IL-1β was significantly upregulated in the colon tissues (p<0.05). Compared with the DSS+corn oil group, the DSS+Nic group showed significant reductions in body weight loss, DAI score, colon shortening, and spleen index (p<0.05), along with ameliorated histopathological damage, increased expression of MUC2 and Occludin, decreased infiltration of MPO⁺ cells and F4/80⁺ cells (p<0.05), and downregulated expression of S100A4 and IL-1β in the colon tissues (p<0.05).Conclusion Niclosamide alleviates DSS-induced colitis in mice by inhibiting S100A4.