{
  "abstract": "Background: The high mortality of severe acute pancreatitis (SAP) is primarily driven by multiple organ dysfunction, particularly acute lung injury (ALI), a condition for which lacks specific pharmacological therapy. Ginsenoside Re (Re) has documented anti-inflammatory and antioxidant properties, with preliminary evidence indicating its protective potential in pancreatic injury. However, its precise therapeutic efficacy and underlying mechanisms in SAP, especially concerning the mitigation of systemic complications, remain incompletely understood. Purpose: This study aimed to investigate the therapeutic potential of Re in SAP and to delineate the underlying mechanistic pathway connecting pancreatic acinar cell death to pulmonary injury. Methods: SAP was induced in mice by seven hourly cerulein injections followed by a final lipopolysaccharide challenge, and Re was administered intraperitoneally during the induction period. Primary pancreatic acinar cells (PACs) were isolated, and mouse pulmonary microvascular endothelial cells (PMVECs) were cultured for in vitro studies. Underlying mechanisms were investigated through transcriptomic and network pharmacology analyses, followed by molecular docking and experimental validation. Results: Re treatment significantly alleviated pancreatic injury in SAP mice, with a pronounced reduction in acinar necrosis. Integrated transcriptomic and network pharmacology analyses identified necroptosis as a key target for these effects. Accordingly, Re inhibited RIPK3/MLKL-mediated necroptosis both in vivo and in vitro . The specific RIPK3 inhibitor GSK872 abolished cfDNA release from PACs, indicating that necroptosis is the primary source of cfDNA, and notably, Re mimicked these effects. Acinar cell-derived cfDNA was shown to induce pulmonary endothelial inflammation and barrier dysfunction via activation of the cGAS-STING pathway, effects that were abolished by DNase I. In addition, correlation analysis showed that mouse serum cfDNA levels were positively correlated with lung injury parameters. Further pulmonary transcriptomic analysis confirmed that Re treatment suppressed cfDNA-triggered activation of the cGAS-STING signaling in vivo , thereby contributing to the significant attenuation of lung injury. Conclusion: Our study uncovers a novel pathological axis in SAP-ALI, wherein pancreatic necroptosis drives cfDNA release, which subsequently activates the pulmonary endothelial cGAS-STING signaling, ultimately leading to distant lung injury. Re interrupts this cascade at multiple nodes, primarily by inhibiting acinar necroptosis and thereby limiting cfDNA release, which in turn attenuates both local and systemic organ injuries. Together, these findings elucidate a novel mechanistic basis for SAP-ALI and support Re as a promising multi-target therapeutic agent for SAP.",
  "abstract_shown": true,
  "affiliations": [
    "West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China; Corresponding author.",
    "West China Center of Excellence for Pancreatitis, Institute of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China",
    "Core Facilities of West China Hospital, Sichuan University, Chengdu, 610041, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Cheng Hu"
    },
    {
      "affs": [
        1
      ],
      "name": "Rui Yang"
    },
    {
      "affs": [
        1
      ],
      "name": "Wenjuan Luo"
    },
    {
      "affs": [
        2
      ],
      "name": "Mingjie Xu"
    },
    {
      "affs": [
        1
      ],
      "name": "Tian Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Xinwei Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Yuxin Shen"
    },
    {
      "affs": [
        1
      ],
      "name": "Shihang Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Lihui Deng"
    },
    {
      "affs": [
        0
      ],
      "name": "Qing Xia"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ezm6m3y5jdrv3.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jgr.2026.101121",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S1226845326001478",
  "id": "ezm6m3y5jdrv3",
  "issns": [
    "1226-8453",
    "2093-4947"
  ],
  "landing_url": "https://doi.org/10.1016/j.jgr.2026.101121",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
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      "lcc",
      "QK1-989"
    ],
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      "openalex",
      "2746|Pancreatitis Pathology and Treatment"
    ]
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  "openalex": "W7202073574",
  "pdf_url": "https://europepmc.org/articles/PMC13711401?pdf=render",
  "pmcid": "PMC13711401",
  "pmid": "42948587",
  "published": "2026-08-10",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/ezm6m3y5jdrv3.ris",
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    {
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2746|Pancreatitis Pathology and Treatment",
      "subfield": "surgery"
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  ],
  "title": "Ginsenoside Re attenuates severe acute pancreatitis-associated acute lung injury by inhibiting pancreatic necroptosis-driven cfDNA release and pulmonary cGAS-STING activation",
  "title_text": "Ginsenoside Re attenuates severe acute pancreatitis-associated acute lung injury by inhibiting pancreatic necroptosis-driven cfDNA release and pulmonary cGAS-STING activation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:11Z",
  "url": "https://research.draconitic.com/paper/ezm6m3y5jdrv3",
  "venue": "Journal of Ginseng Research",
  "versions": []
}