Saposhnikovia divaricata Inhibits Inflammation, Oxidative Stress, and Ferroptosis to Alleviate DSS-Induced Ulcerative Colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that seriously jeopardizes health. Saposhnikovia divaricata (FF) has anti-inflammatory and antioxidant pharmacological effects. Numerous studies have demonstrated the efficacy of FF in alleviating UC, but the potential mechanism by which inhibiting ferroptosis alleviates UC remains unclear. This research aims to investigate the ways in which FF regulates inflammation, oxidative stress and ferroptosis to attenuate UC. Firstly, the chemical compounds of FF were identified by UPLC-Q-Orbitrap HRMS. FF significantly reduced levels of nitric oxide (NO), proinflammatory cytokines and reactive oxygen species (ROS) in the lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophage cells. We used 3% Dextrose sulfate sodium (DSS) to establish the UC model in C57BL/6 mice. FF (8.4 g/kg) effectively ameliorated the symptoms of weight loss and colon damage, significantly attenuating oxidative stress and modulated the levels of ferroptosis markers in the colon. Moreover, FF can down-regulate the expression of p53 protein and up-regulate the expression of SLC7A11 and GPX4 proteins. The results showed that FF can inhibit inflammation, oxidative stress, and ferroptosis to alleviate DSS-induced UC, by regulating the p53 signaling pathway.