{
  "abstract": "ObjectiveTo evaluate the potential preventive effects of Guizhi-Shaoyao-Zhimu Decoction (GSZD) on gastrointestinal acute graft-vs.-host disease (GI-aGVHD) and explore its potential mechanisms.MethodsBioactive compounds and putative targets of GSZD were identified by network pharmacology. aGVHD-associated genes were retrieved from public databases, and gut damage-associated genes were identified by integrating differential expression analysis and WGCNA of two public transcriptomic datasets. Protein-protein interaction network construction, enrichment analyses, and molecular docking were performed. The effects of GSZD and the potential involvement of FGF2/PI3K/Akt signaling pathway were assessed in an aGVHD mouse model.ResultsA total of 183 candidate compounds and 705 GSZD targets were identified. Database mining and transcriptomic analyses identified 816 aGVHD-associated genes and 161 gut damage-associated genes. Intersection analysis revealed 109 targets shared between GSZD and aGVHD, and 11 targets shared between GSZD and aGVHD gut damage. Network and enrichment analyses highlighted AKT1, FGF2, and PI3K/Akt signaling pathway for further evaluation. Exploratory molecular docking provided predicted rankings for 31 AKT1-compound pairs and two FGF2-compound pairs. In vivo, compared with untreated aGVHD mice, mice treated with GSZD showed prolonged survival, reduced body weight loss, milder clinical manifestations and intestinal pathological injury, less pronounced cytokine dysfunction, improved indices of gut barrier integrity, lower FGF2 levels and PI3K/Akt phosphorylation. Exogenous FGF2 supplementation alone did not significantly worsen aGVHD, but partially reversed the protective effects of GSZD in GSZD-treated mice, accompanied by reactivation of PI3K/Akt signaling.ConclusionGSZD showed preventive effects against GI-aGVHD in a murine aGVHD model. These effects were accompanied by attenuated inflammatory responses and reduced FGF2/PI3K/Akt signaling, suggesting that this axis may contribute to the protective effects of GSZD.",
  "abstract_shown": true,
  "affiliations": [
    "Medical Center of Hematology, The Second Affiliated Hospital of Army Medical University, Chongqing, China",
    "Chongqing Key Laboratory of Hematology and Microenvironment, Chongqing, China",
    "Department of Hematology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China",
    "Jinfeng Laboratory, Chongqing, China"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xingyu Wan"
    },
    {
      "affs": [
        1
      ],
      "name": "Xingyu Wan"
    },
    {
      "affs": [
        0
      ],
      "name": "Nan Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Nan Li"
    },
    {
      "affs": [
        2
      ],
      "name": "Xueqing Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Wuchen Yang"
    },
    {
      "affs": [
        1
      ],
      "name": "Wuchen Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuiqing Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Shuiqing Liu"
    },
    {
      "affs": [
        0
      ],
      "name": "Xi Zhang"
    },
    {
      "affs": [
        1
      ],
      "name": "Xi Zhang"
    },
    {
      "affs": [
        3
      ],
      "name": "Xi Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5ywb8rcyn9pyr.bib",
  "cited_by": 0,
  "doi": "10.3389/fmed.2026.1908959",
  "fulltext_url": "https://www.frontiersin.org/articles/10.3389/fmed.2026.1908959/full",
  "id": "5ywb8rcyn9pyr",
  "issns": [
    "2296-858X"
  ],
  "landing_url": "https://doi.org/10.3389/fmed.2026.1908959",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "R5-920"
    ],
    [
      "openalex",
      "2720|Hematopoietic Stem Cell Transplantation"
    ]
  ],
  "openalex": "W7223396300",
  "pdf_url": "https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2026.1908959/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-23",
  "publisher": "Frontiers Media S.A.",
  "ris": "https://research.draconitic.com/paper/5ywb8rcyn9pyr.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:13Z",
      "native_id": "ee5160b36e934eb38f725a60d71f6181",
      "source": "doaj",
      "url": "https://doi.org/10.3389/fmed.2026.1908959"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2720|Hematopoietic Stem Cell Transplantation",
      "subfield": "general"
    }
  ],
  "title": "Guizhi-Shaoyao-Zhimu decoction alleviates gastrointestinal acute graft-vs.-host disease and suppresses FGF2/PI3K/Akt signaling: insights from network pharmacology, WGCNA, molecular docking, and animal experiment",
  "title_text": "Guizhi-Shaoyao-Zhimu decoction alleviates gastrointestinal acute graft-vs.-host disease and suppresses FGF2/PI3K/Akt signaling: insights from network pharmacology, WGCNA, molecular docking, and animal experiment",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:43:13Z",
  "url": "https://research.draconitic.com/paper/5ywb8rcyn9pyr",
  "venue": "Frontiers in Medicine",
  "versions": []
}