{
  "abstract": "Background Coronary heart disease (CHD) is the most prevalent and fatal cardiovascular disorder, with myocardial ischemia/reperfusion injury (MIRI) as its core pathogenic mechanism. Madecassic acid (MA), a pentacyclic triterpenoid isolated from Centella asiatica, has shown prominent cardioprotective activity. Nevertheless, the precise regulatory mechanisms underlying the protective effects of MA against MIRI remain to be elucidated. Methods A natural compound library was employed to screen natural drugs with anti-MIRI activity. The therapeutic efficacy of MA was evaluated in a primary cardiomyocyte hypoxia/reoxygenation model and a murine myocardial ischemia/reperfusion model. A series of experimental assays were applied to systematically assess the inflammatory response, mitochondrial function, and modes of cell death. RNA-seq, co-immunoprecipitation assays, and siRNA-mediated interference were utilized to explore downstream target molecules. Target gene knockout experiments were performed to validate the pharmacological effects and potential molecular mechanisms of MA. Results Through a well-established drug screening system, MA was identified as a promising compound that exerts a significant protective effect against MIRI. In vitro and in vivo experiments demonstrated that MA exerts potent cardioprotection through a hierarchical signaling network governed by DDX17. Mechanistically, MA modulates mitochondrial homeostasis and energy metabolism via a multi-pathway mechanism, and significantly suppresses reactive oxygen species (ROS) accumulation, thereby ultimately alleviating autophagic flux blockade and cardiomyocyte apoptosis. Furthermore, MA promotes the interaction between DDX17 and heat shock protein 90 (HSP90), which in turn enhances the phosphorylation of dynamin-related protein 1 (DRP1) at Ser637 and suppresses the expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), thus preventing cardiomyocyte ferroptosis. Conclusions Collectively, this study identifies MA as a novel natural compound that activates DDX17 through multi-pathway regulation to attenuate oxidative stress, stabilize energy metabolism, and ultimately mitigate MIRI-induced cardiomyocyte death. These findings provide novel insights into the regulatory roles of DDX17 in cardiac injury and establish the translational medical potential of MA as a DDX17-targeting agent for the intervention of cardiovascular diseases. Graphical abstract",
  "abstract_shown": true,
  "affiliations": [
    "Department of Basic Innovation Research, Beijing Hospital, National Center for Gerontology; National Clinical Research Center for Gerontology; The Key Laboratory of Geriatrics of NHC; Beijing Key Laboratory of Aging Mechanism and Intervention Research On Aging-Related Diseases, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College",
    "Department of Cardiology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College",
    "School of Life Sciences, North China University of Science and Technology",
    "Department of Urology, People’s Hospital, Peking University",
    "Independent Cardiovascular Research Lab, Chinese Institutes for Medical Research, Capital Medical University"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 20,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Wenlin Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Sainan Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Lin Dou"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiuqing Huang"
    },
    {
      "affs": [
        0
      ],
      "name": "Kun Xu"
    },
    {
      "affs": [
        1
      ],
      "name": "Que Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Dachuan Guo"
    },
    {
      "affs": [
        0
      ],
      "name": "Xingyun Jiao"
    },
    {
      "affs": [
        1
      ],
      "name": "Liwei Zhang"
    },
    {
      "affs": [
        2
      ],
      "name": "Yang Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ju Cui"
    },
    {
      "affs": [
        0
      ],
      "name": "Yong Man"
    },
    {
      "affs": [
        1
      ],
      "name": "Deping Liu"
    },
    {
      "affs": [
        1
      ],
      "name": "Tong Zou"
    },
    {
      "affs": [
        1
      ],
      "name": "Xue Yu"
    },
    {
      "affs": [
        0
      ],
      "name": "Liang Sun"
    },
    {
      "affs": [
        3
      ],
      "name": "Qiang Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Jian Li"
    },
    {
      "affs": [
        4
      ],
      "name": "Junpeng Gao"
    },
    {
      "affs": [
        0
      ],
      "name": "Tao Shen"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3mywdf5d9rdr2.bib",
  "cited_by": 0,
  "doi": "10.1186/s11658-026-00950-8",
  "fulltext_url": "https://doi.org/10.1186/s11658-026-00950-8",
  "id": "3mywdf5d9rdr2",
  "issns": [
    "1689-1392",
    "1425-8153"
  ],
  "landing_url": "https://doi.org/10.1186/s11658-026-00950-8",
  "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",
      "QH573-671"
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      "openalex",
      "2705|Cardiac Ischemia and Reperfusion"
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  "openalex": "W7171665603",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/3mywdf5d9rdr2.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T14:20:58Z",
      "native_id": "0167040735544861afb1c4d1afa32dbf",
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  "subjects": [
    {
      "field": "medicine",
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      "subfield": "cardiovascular"
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  ],
  "title": "Madecassic acid orchestrates DDX17-dependent pathway suppression of ferroptosis to mitigate myocardial ischemic/reperfusion injury",
  "title_text": "Madecassic acid orchestrates DDX17-dependent pathway suppression of ferroptosis to mitigate myocardial ischemic/reperfusion injury",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T14:20:58Z",
  "url": "https://research.draconitic.com/paper/3mywdf5d9rdr2",
  "venue": "Cellular & Molecular Biology Letters",
  "versions": []
}