Five-flavor Sophora flavescens Enteric-coated Capsules Alleviate Experimental Colitis and Ferroptosis-related Changes

Ulcerative colitis remains difficult to manage because effective and targeted therapeutic options are limited, and oxidative stress, inflammatory signaling, and regulated cell-death pathways may contribute to mucosal injury. This study evaluated whether five-flavor Sophora flavescens enteric-coated capsules (FSEC) alleviate experimental colitis and explored associated changes in oxidative stress, inflammation, and markers of ferroptosis. A mouse model of ulcerative colitis was established using cyclic exposure to 2.5% dextran sulfate sodium, combined with tumor necrosis factor alpha challenge. Mice were treated with low-, medium-, or high-dose FSEC or with the TLR4 antagonist CRX-526 as a positive-control intervention. Colon histopathology was assessed by hematoxylin and eosin staining. Serum superoxide dismutase, catalase, glutathione, myeloperoxidase, and Fe²⁺ levels were measured using biochemical assays. Colon tissue cytokines were quantified by enzyme-linked immunosorbent assay, JAK2 and STAT3 expression were evaluated by immunohistochemistry, and GPX4, FTH1, and ACSL4 expression were analyzed by western blotting. FSEC treatment reduced colonic mucosal injury and inflammatory-cell infiltration, increased antioxidant indices, and decreased myeloperoxidase levels. FSEC also reduced TNF-α and IL-1α levels, partially restored IL-13 levels, and was associated with weaker JAK2 and STAT3 immunostaining. In parallel, FSEC improved ferroptosis-related marker changes, including reduced Fe²⁺ and ACSL4 levels and increased GPX4 and FTH1 expression. These findings suggest that FSEC alleviates experimental ulcerative colitis in mice, at least in part by improving oxidative-stress status, moderating inflammatory signaling, and restoring ferroptosis-related marker profiles.