Seliciclib alleviates ulcerative colitis by inhibiting ferroptosis and improving intestinal inflammation

Ulcerative colitis (UC) is a chronic, recurrent, non-specific inflammatory disease, and the pathogenesis of the disease remains unclear. Ferroptosis is a form of programmed cell death characterized by the accumulation of iron-dependent lipid peroxides, which are simultaneously closely related to reactive oxygen species (ROS). Although seliciclib is highly effective against immune inflammation, its mechanism on colitis is unclear. This study demonstrated that seliciclib administration partially inhibited ferroptosis, alleviating symptoms and inflammation in experimental colitis.

The mouse UC model was induced by 3.0 % dextran sodium sulfate (DSS) for 7 days and treated with seliciclib (10 mg/kg) for 5 days. In the in vitro model, LPS (100 μg/mL) was used for induction and seliciclib (10 μM) was applied for 2 h. Meanwhile, appropriate histopathology, inflammatory response, oxidative stress, and ferroptosis regulators were measured.

This study primarily investigated the role of seliciclib in regulating ferroptosis in UC. Bioinformatics analysis indicated that Dual oxidase 2 (DUOX2) may serve a role involved in the ferroptosis of UC. The experimental findings demonstrated that seliciclib alleviates symptoms and inflammation in DSS-induced UC mice and partially mitigates the occurrence of ferroptosis both in vivo and in vitro, possibly through the modulation of DUOX2.

Ferroptosis is strongly associated with the development of colitis, and seliciclib plays an essential role in ferroptosis and inflammation in UC. The suppression of ferroptosis in the intestinal epithelium could be a therapeutic approach for UC.