Cucurbitacin B alleviates DSS-induced experimental colitis by targeting ZNF70 to suppress the NLRP3/STAT3 signaling axis.

Ulcerative colitis (UC) is an inflammatory disease characterized by lifelong involvement and a complex pathogenesis. Due to the limitations of current treatment modalities, there remains a pressing need to discover new medications for the management of UC. Cucurbitacin B (CuB) is a tetracyclic triterpenoid derived from Lagenaria siceraria (Molina) Standl., exhibiting pharmacological activities including hepatoprotective, anti-inflammatory, and anti-tumor properties. In this study, we conducted a comprehensive evaluation of the anti-inflammatory activity of CuB in both DSS-induced experimental colitis in vivo and macrophage models in vitro. Our results indicate that CuB exerts an anti-inflammatory effect by regulating the assembly of the NLRP3 inflammasome and the activation of p-STAT3 via ZNF70, thereby reducing the release of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Such results indicate that CuB can effectively prevent the development of UC and offer new insights for its management.