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

Zhaohan Wang; Yanru Xiang; Tao Yu; Kun Liu; Wang Li; Shirong Zhong

doi:10.3791/70711

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Research Article

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

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DOI:

10.3791/70711

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June 23rd, 2026

Zhaohan Wang¹ , Yanru Xiang² , Tao Yu¹ , Kun Liu³ , Wang Li⁴ , Shirong Zhong⁵

¹Department of Gastroenterology and Hepatology, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, ²Department of Integrated Traditional Chinese and Western Medicine, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College, ³Department of Gastroenterology and Hepatology, Pengze County People's Hospital, ⁴Department of Gastroenterology and Hepatology, General Hospital of Pingxiang Mining Group Company, ⁵Department of Rehabilitation Medicine, Jiangxi Provincial People's Hospital, The First Affiliated Hospital of Nanchang Medical College

Summary

In a mouse model of ulcerative colitis, five-flavor Sophora flavescens enteric-coated capsules alleviated colonic injury and improved oxidative stress, inflammatory cytokine imbalance, JAK2/STAT3 signaling, and changes in ferroptosis-related markers.

Abstract

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.

Introduction

Ulcerative colitis (UC) is a chronic inflammatory disorder that primarily affects the colonic and rectal mucosa and is characterized by recurrent episodes of mucosal inflammation, ulceration, and impaired barrier function¹^,²^,³. Although genetic susceptibility, environmental factors, epithelial barrier dysfunction, and immune dysregulation have been implicated in UC pathogenesis, the mechanisms underlying persistent mucosal injury remain incompletely understood. Current pharmacological treatments, including aminosalicylates, corticosteroids, immunosuppressants, and biologic ag....