Curcumin attenuates ulcerative colitis via regulation of Sphingosine kinases 1/NF‐κB signaling pathway

Abstract Curcumin, a compound from Curcuma longa L., has significant anti‐inflammatory properties. However, the mechanisms underlying its anti‐inflammatory activity in dextran sodium sulfate (DSS)‐induced ulcerative colitis (UC) remain inadequately understood. This study aimed to further elucidate the molecular mechanisms of curcumin DSS‐induced UC mice. Our data showed that curcumin alleviated DSS‐induced colitis by reducing intestinal damage and inflammation, increasing goblet cells in colon tissues. Enzyme‐linked immunosorbent assay revealed that curcumin reduced the expression of inflammatory cytokines (tumor necrosis factor‐alpha, interleukin‐1β, and interleukin‐8) in serum and myeloperoxidase in colon tissues. A comprehensive analysis integrating network pharmacology and RNA sequencing (RNA‐seq) revealed significant enrichment of the nuclear factor kappa B (NF‐κB) signaling pathways. Notably, RNA‐seq analysis demonstrated that curcumin significantly downregulated the mRNA expression of sphingosine kinase 1 (SphK1). Furthermore, molecular docking analysis showed that curcumin can bind to SphK1 and NF‐κB. Additionally, curcumin was found to inhibit the activation of the SphK1/NF‐κB signaling pathway in DSS‐induced UC colon tissue. This study addresses pharmacologic and mechanistic perspectives of curcumin that ameliorates DSS‐induced UC and inflammatory response.