{
  "abstract": "Background: Graves’ disease (GD) is initiated by thyroid-stimulating hormone receptor autoantibody signaling, whereas cytokine-mediated inflammation within the thyroid may amplify thyrocyte activation. The microbiota-related metabolites contributing to this inflammatory component remain incompletely defined.\n\nMethods: We integrated reported gut microbiota–metabolite associations with GD-associated genes, constructed protein–protein interaction and enrichment networks, prioritized candidate metabolites, and evaluated predicted docking of isoquercetin (ISO) with inflammatory targets. Two-sample Mendelian randomization (MR) used MiBioGen microbiota and FinnGen autoimmune hyperthyroidism data. A separate four-group experiment compared control, M22 alone, interferon-γ (IFN-γ) alone, and combined M22/IFN-γ stimulation in Nthy-ori 3–1 thyroid follicular epithelial cells. ISO treatment was then evaluated under combined stimulation; inflammatory transcripts, NF-κB p65 phosphorylation, and cell viability were assessed.\n\nResults: Fifty-three shared targets were identified, and the highest-degree PPI nodes included IL6, TNF, AKT1, IL1B, JUN, NFKB1, TP53, and CASP3. The shared targets were enriched in TNF, NF-κB, MAPK, PI3K-Akt, and Th17-related pathways. After chemical-name standardization, ISO had a network degree of 8 and was connected with TNF and IL6; docking indicated predicted molecular compatibility rather than direct binding. Twelve taxa showed nominal IVW associations with GD, but none survived false discovery rate correction. In the four-group experiment, IFN-γ was the dominant stimulus for IL1B, IL6, and TNF expression; the combined M22/IFN-γ group had the highest mean expression, but no interaction term was significant. Under combined stimulation, ISO reduced inflammatory transcripts and the phospho-p65/total p65 ratio without markedly changing total p65.\n\nConclusion: These exploratory, convergent findings identify ISO as a microbiota-related candidate modulator of thyroid epithelial inflammatory responses. They do not establish microbial production, direct target binding, or clinical efficacy, and require further mechanistic and in vivo validation.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Shihan Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Qunwei Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaoyu Ding"
    },
    {
      "affs": [
        0
      ],
      "name": "Xinzhong Zhang",
      "orcid": "0000-0002-0365-1226"
    },
    {
      "affs": [
        0
      ],
      "name": "Guang Wang",
      "orcid": "0000-0002-9660-3425"
    },
    {
      "affs": [
        0
      ],
      "name": "Jia Liu",
      "orcid": "0009-0000-0429-5748"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d1ze2eeng7sgy.bib",
  "cited_by": 0,
  "doi": "10.2147/jir.s643441",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13730083/",
  "id": "d1ze2eeng7sgy",
  "issns": [
    "1178-7031"
  ],
  "landing_url": "https://doi.org/10.2147/jir.s643441",
  "language": "en",
  "licence": "CC-BY-NC-4.0",
  "licence_label": "CC BY-NC 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2712|Thyroid Disorders and Treatments"
    ]
  ],
  "openalex": "W7224947311",
  "pdf_url": "https://www.dovepress.com/article/download/121625",
  "pmcid": "PMC13730083",
  "pmid": "42979521",
  "published": "2026-10-30",
  "publisher": "Dove Press",
  "ris": "https://research.draconitic.com/paper/d1ze2eeng7sgy.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:22:43Z",
      "native_id": "PMC13730083",
      "source": "pmc",
      "url": "https://doi.org/10.2147/jir.s643441"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2712|Thyroid Disorders and Treatments",
      "subfield": "endocrinology-metabolism"
    }
  ],
  "title": "Isoquercetin Attenuates Graves’ Disease-Related Thyroid Epithelial Inflammatory Responses: Exploratory Evidence from Network Pharmacology, Mendelian Randomization, and Cellular Validation",
  "title_text": "Isoquercetin Attenuates Graves’ Disease-Related Thyroid Epithelial Inflammatory Responses: Exploratory Evidence from Network Pharmacology, Mendelian Randomization, and Cellular Validation",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:22:43Z",
  "url": "https://research.draconitic.com/paper/d1ze2eeng7sgy",
  "venue": "Journal of Inflammation Research",
  "versions": []
}