Saikosaponin B1/D alleviate dextran sulfate sodium- induced colitis via regulating the NRF2/HO-1 pathway to inhibit the ferroptosis in zebrafish

Background: Inflammatory bowel disease (IBD) is a chronic and recurrent gastrointestinal inflammation, the pathophysiological mechanisms of that is not fully understood, and the current conventional treatment drugs are often associated with serious side effects. Saikosaponins(SSs) are the main active component of Bupleurum chinense DC. (BC). Saikosaponin A has been reported to have a positive effect on the remission of DSS induced colitis. Aim: However, the studies on the mechanism and safety of SSs are still limited. Materials and methods: We established zebrafish colitis model induced by sodium glucan sulfate (DSS) and gave intervention treatment with different saikosaponins. Results : It was found that saikosaponin B1 (SSB1) and saikosaponin D (SSD) had the most prominent inhibitory ability on neutrophils infiltration in the larval intestine among the 6 saikosaponin monomers. In this study, we explored the effect and mechanism of SSB1 and SSD on DSS induced colitis in zebrafish. The results showed that both SSB1 and SSD could reduce the histological injury, tissue inflammatory cytokines and ROS expression in zebrafish. Moreover, we observed that both SSB1 and SSD significantly inhibited ferroptosis in DSS stimulated zebrafish colitis. In Conclusion: conclusion, our results suggested that Saikosaponin B1/D play a protective role in inhibiting ferroptosis by up-regulating NRF2/HO-1 pathway.