{
  "abstract": "Background: Intestinal ischemia–reperfusion injury (IIRI) is driven by oxidative stress, excessive inflammation, Endoplasmic Reticulum Stress (ERS), and disruption of the intestinal epithelial barrier. Corilagin, a natural ellagitannin with antioxidant and anti-inflammatory activities, has shown protective effects against IIRI; however, its cross-species and multitarget mechanisms remain unclear.\n\nMethods: This study investigated the protective mechanisms of Corilagin against IIRI by integrating Corilagin-related targets, IIRI-associated genes, and an ERS gene set. Differential expression analyses of GSE37013 and GSE96733 were combined with an ensemble machine-learning framework comprising 15 algorithms to prioritize core genes. Molecular docking and 100-ns all-atom molecular dynamics simulations using the AlphaFold-predicted full-length human NRF2 structure were performed to assess the predicted Corilagin-NRF2 interaction. A mouse IIRI model was used to validate selected molecular and histological findings by histology, RT-qPCR, Western blotting, and immunohistochemistry. In IEC-6 cells subjected to OGD/R, NRF2 immunofluorescence and siRNA-mediated knockdown of Nrf2 or Abcg2 were used to further evaluate the involvement of NRF2 and ABCG2 in Corilagin-mediated protection.\n\nResults: Intersection analysis identified 472 genes shared among Corilagin-related targets, IIRI-related genes, and ERS-associated genes. Enrichment analysis highlighted stress- and injury-related pathways, including PI3K-Akt signaling. Ensemble machine learning prioritized 12 core genes across human and mouse datasets, with ABCG2, IL10, and PRKCZ emerging as prominent candidates. Docking and 100-ns MD simulations supported persistent Corilagin retention within the predicted NRF2 binding region, while post-relaxation MM/GBSA analysis indicated favorable interaction energetics. In vivo , Corilagin pretreatment reduced inflammation and oxidative stress-related changes, restored apical ABCG2 and tight-junction protein expression, improved mucosal morphology, and altered CHOP expression. In IEC-6 cells, Nrf2 or Abcg2 knockdown weakened Corilagin-mediated preservation of Occludin, Claudin-1, and ZO-1 under OGD/R, supporting NRF2–ABCG2 involvement in this protective response.\n\nConclusion: Corilagin may alleviate IIRI by modulating ERS-related molecular changes and preserving the intestinal epithelial barrier with NRF2 and ABCG2 contributing to a candidate regulatory module involved in this protective response. These findings provide computational and experimental support for further investigation of Corilagin as a potential intervention for IIRI and illustrate the value of combining multi-source data integration with ensemble machine learning to characterize the multitarget pharmacology of natural products.",
  "abstract_shown": true,
  "affiliations": [
    "Institute (College) of Integrative Medicine, Dalian Medical University , ,",
    "College of Pharmacy, Dalian Medical University , ,",
    "School of Chemistry and Chemical Engineering, Liaoning Normal University , ,",
    "College of Advance Institute For Medical Science, Dalian Medical University , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Zhiyang Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Qin Han"
    },
    {
      "affs": [
        2
      ],
      "name": "Lijie Pang"
    },
    {
      "affs": [
        3
      ],
      "name": "Siyang Zheng"
    },
    {
      "affs": [
        1
      ],
      "name": "Xin Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Bin Tian"
    },
    {
      "affs": [
        2
      ],
      "name": "Kun Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Bin Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Feng Qiu"
    },
    {
      "affs": [
        1
      ],
      "name": "Yunpeng Diao"
    },
    {
      "affs": [
        0
      ],
      "name": "Ruqiang Yuan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dscded6p7c28e.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1966534",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13691303/?tool=EBI",
  "id": "dscded6p7c28e",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13691303",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Genomics, phytochemicals, and oxidative stress"
    ]
  ],
  "openalex": "W7221186327",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13691303/pdf/?tool=EBI",
  "pmcid": "PMC13691303",
  "pmid": null,
  "published": "2026-10-09",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/dscded6p7c28e.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:59Z",
      "native_id": "PMC:PMC13691303",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13691303"
    },
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1966534",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1966534/full"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Genomics, phytochemicals, and oxidative stress",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Multi-source data integration and ensemble machine learning analysis of the role of Corilagin in regulating endoplasmic reticulum stress and alleviating intestinal ischemia reperfusion injury in mice",
  "title_text": "Multi-source data integration and ensemble machine learning analysis of the role of Corilagin in regulating endoplasmic reticulum stress and alleviating intestinal ischemia reperfusion injury in mice",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:06Z",
  "url": "https://research.draconitic.com/paper/dscded6p7c28e",
  "venue": "Frontiers in pharmacology",
  "versions": []
}