DXFD-1 alleviates DSS-induced ulcerative colitis by targeting NF-κB and Nrf2 signaling

Ulcerative colitis (UC) is one of the most common intestinal disorders. Its pathological mechanisms are complex and involve multiple cellular signaling pathways. Among these, NF-κB and Nrf2 signaling pathways play significant roles in the pathogenesis of UC. Currently, there are not many types of medications available for the treatment of UC. Although traditional therapeutic agents have anti-inflammatory effects, they also have many adverse reactions. Therefore, there is an urgent need for new research drugs to treat UC. This study aims to investigate the effects of a novel hydrogen sulfide-releasing small molecule compounds, DXFD-1, on UC and its potential mechanisms. In vitro experiments were conducted to establish an inflammation model using LPS-stimulated RAW264.7 cells. In vivo model of UC in mice was established using dextran sulfate sodium (DSS). The results of in vivo and in vitro experiments indicated that DXFD-1 could inhibit oxidative stress by activating the Nrf2 signaling, increasing the levels of SOD and GSH-PX, and reducing the levels of ROS, MPO, and MDA. Meanwhile, DXFD-1 significantly decreased the expression of TNF-α, IL-6, and IL-1β, downregulating the NF-κB signaling. These results demonstrate that DXFD-1 exhibits potent anti-inflammatory and anti-oxidative stress effects, and its potential mechanism related to the inhibition of the NF-κB signaling and the activation of the Nrf2 signaling. Therefore, DXFD-1 is expected to become a lead compound for the clinical treatment of UC.