Vitexin, one of the major active components in hawthorn, has been shown to possess multiple pharmacological activities. Here, we sought to investigate the effect of vitexin on an ameliorating dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) mouse model and further explored its potential mechanism. The results indicated that vitexin administration could significantly alleviate the signs of colitis via suppressing body weight loss, reducing disease activity index (DAI) score, and mitigating colonic damage. Also, vitexin treatment in colitis mice markedly inhibited the production of pro-inflammation cytokines (such as IL-1β, IL-6, and TNF-α). Meanwhile, vitexin also could markedly down-regulate the phosphorylation levels of p65, IκB, and STAT1. Moreover, vitexin also dose-dependently increased the expressions of muc-2, ZO-1, and occludin proteins in colonic tissues of colitis mice. Further studies revealed that vitexin dramatically modulated the disturbed intestinal flora in colitis mice. Vitexin is beneficial for regulating abundances of some certain bacteria, such as Bacteroides, Helicobacter, Alistipes, Lachnospiraceae_NK4A136_group, and Lachnospiraceae_UCG-006. Interestingly, the correlation analysis indicated that key microbes were strongly correlated with colitis features, such as pro-inflammatory cytokines and gut barrier. Collectively, these results demonstrated that vitexin treatment alleviated inflammation, intestinal barrier dysfunction, and intestinal flora dysbiosis in colitis mice. Vitexin is expected to be a promising compound for UC treatment.

Patients with ulcerative colitis (UC) have been found to be frequently associated with secondary liver injury (SLI). In this study, we investigated the protective effect of GA on dextran sodium sulfate (DSS)-induced SLI in mice and its mechanism. The SLI was established by adding 4% DSS in the drinking water of mice, and the effects of GA (5, 20 mg/kg, p.o., once a day for 7 days) in hepatic tissues were analyzed. HepG2 cells were induced by lipopolysaccharide (LPS) to detect the effect of GA on ferroptosis and the underlying mechanism. Pathological damage was determined by H&E. Liver parameters (AST and ALT), antioxidant enzyme activities (MDA and SOD), and the level of Fe2+ in the liver were detected by kits. Cytokine levels (TNF-α, IL-1β, and IL-6) and Gpx4 activity in the liver were detected by ELISA. Finally, the activation of nuclear factor erythroid 2-like 2 (Nrf2) was detected to explore the mechanism. The results indicated that GA significantly attenuated DSS-induced hepatic pathological damage, liver parameters, and cytokine levels and increased the antioxidant enzyme activities. Moreover, GA attenuated ferroptosis in DSS-induced liver injury and upregulated Gpx4 expression in DSS-induced mice. Mechanistic experiments revealed that GA activated Nrf2 in mice. Taken together, this study demonstrates that GA can alleviate ferroptosis in SLI in DSS-induced colitis mice, and its protective effects are associated with activating the Nrf2–Gpx4 signaling pathway.