Psoralen alleviates ulcerative colitis by suppressing inflammation, modulating oxidative stress, and regulating ferroptosis.

OBJECTIVE

This study aimed to systematically evaluate the therapeutic effects of Psoralen (PSO) on ulcerative colitis (UC) and investigate its underlying mechanisms, with a particular focus on intestinal barrier function, gut microbiota, inflammation, oxidative stress, and ferroptosis.

METHODS

UC was induced in mice via 2.25 % dextran sulfate sodium (DSS). The therapeutic efficacy of PSO was assessed by monitoring body weight, disease activity index (DAI), colon length, and histopathological alterations. Intestinal barrier integrity was evaluated through tight junction protein expression and permeability assays. Changes in gut microbiota were analyzed by 16S rDNA sequencing. Inflammatory cytokines, oxidative stress markers, and ferroptosis-related proteins were quantified by ELISA and Western blot.

RESULTS

PSO significantly mitigated UC symptoms, demonstrated by reduced weight loss, decreased DAI scores, prolonged colon length, and improved histopathology. It reinforced intestinal barrier integrity by upregulating ZO-1, Claudin-1, and Occludin while reducing permeability. PSO modulated gut microbiota by promoting beneficial bacteria and inhibiting pathogenic species. Additionally, it suppressed the expression of IL-6, TNF-α, and IL-1β and inhibited the TLR4/MyD88/NF-κB and JAK2/STAT3 signaling pathways. PSO also alleviated oxidative stress, as evidenced by decreased ROS and MDA levels, and increased SOD and GSH. It inhibited ferroptosis by reducing Fe2+ accumulation and modulating ferroptosis-related proteins.

CONCLUSION

PSO exerts therapeutic effects on UC through a multi-target mechanism that enhances the intestinal barrier, modulates the gut microbiota, exerts anti-inflammatory actions, mitigates oxidative stress, and inhibits ferroptosis, highlighting its potential as a promising therapeutic candidate.