{
  "abstract": "Objective\n\nTo investigate the therapeutic effect of Tuoli Xiaodu San (TLXDS) on ulcerative colitis (UC) and identify its key molecular target.Methods\n\nA 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 Fe²⁺ 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\n\nTLXDS 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 Fe²⁺ 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\n\nTLXDS 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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Colorectal Surgery, Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 215009, People's Republic of China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhaozheng Zhang",
      "orcid": "0009-0000-6342-7798"
    },
    {
      "affs": [
        0
      ],
      "name": "Xuejiao Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Mengru Hou"
    },
    {
      "affs": [
        0
      ],
      "name": "Ke Wen"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianhua Yang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0zwagvvse7j3g.bib",
  "cited_by": 0,
  "doi": "10.2147/jir.s594705",
  "fulltext_url": "https://europepmc.org/articles/PMC13726638",
  "id": "0zwagvvse7j3g",
  "issns": [
    "1178-7031"
  ],
  "landing_url": "https://europepmc.org/article/MED/42974467",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2740|Ferroptosis and cancer prognosis"
    ]
  ],
  "openalex": "W7224110157",
  "pdf_url": "https://europepmc.org/articles/PMC13726638?pdf=render",
  "pmcid": "PMC13726638",
  "pmid": "42974467",
  "published": "2026-10-29",
  "publisher": "Dove Press",
  "ris": "https://research.draconitic.com/paper/0zwagvvse7j3g.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T15:20:47Z",
      "native_id": "MED:42974467",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42974467"
    },
    {
      "first_seen": "2026-11-05T12:22:56Z",
      "native_id": "PMC13726638",
      "source": "pmc",
      "url": "https://doi.org/10.2147/jir.s594705"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Ferroptosis and cancer prognosis",
      "subfield": "general"
    }
  ],
  "title": "Tuoli Xiaodu San Alleviates Ferroptosis in Ulcerative Colitis via Suppression of the DUOX2/GPX4 Axis.",
  "title_text": "Tuoli Xiaodu San Alleviates Ferroptosis in Ulcerative Colitis via Suppression of the DUOX2/GPX4 Axis.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:22:32Z",
  "url": "https://research.draconitic.com/paper/0zwagvvse7j3g",
  "venue": "Journal of inflammation research",
  "versions": []
}