Work

Tuoli Xiaodu San Alleviates Ferroptosis in Ulcerative Colitis via Suppression of the DUOX2/GPX4 Axis

Year: 2026

Type: article

Abstract: Objective: To investigate the therapeutic effect of Tuoli Xiaodu San (TLXDS) on ulcerative colitis (UC) and identify its key molecular target. Methods: A murine UC model was established to evaluate TLXDS effects. In addition, in vitro experiments using LPS-induced MODE-K cells were performed to further validate the underlying mechanism of TLXDS active compounds. Network pharmacology and differential gene analysis identified DUOX2 as a potential target and quercetin (Que), a major flavonoid active component of TLXDS, as a key candidate compound. Subsequent RT-qPCR, immunohistochemistry, transmission electron microscopy (TEM) analysis of mitochondrial ultrastructural changes, measurement of Fe 2+ content and oxidative stress markers (SOD, MDA, GSH), ROS detection, and Western blot of GPX4 and SLC7A11 expression were conducted to validate the role of DUOX2 in TLXDS-mediated ferroptotic alleviation in UC. A DUOX2 overexpression model was constructed to assess its impact on the anti-inflammatory and anti-ferroptotic effects of TLXDS. Furthermore, the effects of both TLXDS-containing serum and Que were evaluated in LPS-induced MODE-K cells. Results: TLXDS significantly ameliorated body weight loss and elevated disease activity index in UC mice, attenuated colon tissue damage, and reduced IL-6, TNF-α, and IL-1β levels. TLXDS treatment suppressed DUOX2 overexpression in the colon tissue of UC mice, reduced Fe 2+ accumulation, enhanced SOD and GSH levels, decreased MDA levels and ROS production, and alleviated ferroptosis-associated mitochondrial ultrastructural damage, while upregulating GPX4 and SLC7A11. The anti-inflammatory and anti-ferroptotic effects of TLXDS were attenuated upon DUOX2 overexpression. Furthermore, in vitro experiments demonstrated that both TLXDS-containing serum and Que similarly reduced inflammation, iron accumulation, and oxidative stress in cells via the DUOX2/GPX4 pathway. Conclusion: TLXDS alleviates UC by inhibiting DUOX2 overexpression, subsequently reducing inflammation and ferroptosis. DUOX2 may serve as a key therapeutic target for TLXDS. Integrating network pharmacology with in vivo experiments provides novel molecular insights into traditional Chinese medicine for UC treatment. Keywords: Tuoli Xiaodu San, ulcerative colitis, DUOX2, ferroptosis, network pharmacology, inflammation

Source: Journal of Inflammation Research

DOI: 10.2147/jir.s594705

Authors: Zhaozheng Zhang, Xuejiao Wang, Mengru Hou, Ke Wen, Jianhua Yang

Institutions: Nanjing University of Chinese Medicine, Suzhou Traditional Chinese Medicine Hospital

Language: English

Topic: Ferroptosis and cancer prognosis

Subfield: Cancer Research

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,836