{
  "abstract": "Background\n\nMyocardial ischemia-reperfusion injury (MIRI) represents a major form of secondary damage during reperfusion therapy, in which inflammation and myocardial fibrosis are key pathological features. Caffeic acid (CA), a natural phenolic compound abundant in dietary sources, has been implicated in cardiovascular protection; however, the mechanisms by which CA modulates post-MIRI inflammation and fibrosis remain insufficiently defined.Objective\n\nTo clarify the molecular target(s) and signaling mechanism(s) through which CA attenuates inflammation-associated myocardial fibrosis after MIRI.Methods\n\nA LAD ligation-based murine MIRI model was used to evaluate the anti-inflammatory and anti-fibrotic efficacy of CA. A co-culture system using cardiac fibroblasts and RAW 264.7 macrophages, along with adoptive cell transfer, was applied to interrogate macrophage-fibroblast crosstalk. Transcriptomic profiling (RNA-seq) was performed to identify candidate pathways involved in CA-mediated protection. Surface plasmon resonance (SPR) assay, CETSA, immunofluorescence, and western blotting were used to assess MAPKs/CREB signaling as a putative intervention axis, and pharmacological activation of MAPKs (anisomycin) or CREB (forskolin), or MAPK14 ablation, was employed to probe pathway involvement.Results\n\nCA improved cardiac function and alleviated inflammatory and fibrotic pathology in MIRI mice, accompanied by suppression of pro-inflammatory cytokines. Conditioned medium from LPS-stimulated RAW 264.7 cells promoted fibroblast activation, and adoptively transferred macrophages within the myocardium promoted fibrotic protein expression; both effects were attenuated by CA. RNA-seq implicated MAPK signaling in the protective mechanism of CA, and downstream analyses supported inhibition of the MAPKs/CREB axis. Notably, CA achieved effects comparable to those of MAPK14 ablation, whereas anisomycin or forskolin partially blunted the anti-inflammatory and anti-fibrotic effects of CA, consistent with functional involvement of MAPKs/CREB signaling in CA-mediated protection during MIRI.Conclusion\n\nCA mitigates MIRI-associated myocardial fibrosis by suppressing MAPKs/CREB-mediated inflammatory signaling, supporting its potential to improve long-term post-MIRI remodeling.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022, China.",
    "Russian-Chinese Education and Research Center of System Pathology, South Ural State University, 76 Lenin Prospekt, Chelyabinsk, 454080, Russia.",
    "Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 106 Pervomaiskaya Street, Yekaterinburg, 620049, Russia.",
    "Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.",
    "Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022, China. yalandong@hust.edu.cn.",
    "Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Ave, Wuhan, 430022, China. desheng.hu@hust.edu.cn.",
    "China-Russia Medical Research Center for Stress Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. desheng.hu@hust.edu.cn."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mi Xiang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaohu Ouyang"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuxin Song"
    },
    {
      "affs": [
        0
      ],
      "name": "Mengling Yang"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Alexey Sarapultsev"
    },
    {
      "affs": [
        3
      ],
      "name": "Shanshan Luo"
    },
    {
      "affs": [
        4
      ],
      "name": "Yalan Dong"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Desheng Hu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bbgwyr30nhb7e.bib",
  "cited_by": 0,
  "doi": "10.1186/s13020-026-01562-2",
  "fulltext_url": "https://europepmc.org/articles/PMC13721419",
  "id": "bbgwyr30nhb7e",
  "issns": [
    "1749-8546"
  ],
  "landing_url": "https://europepmc.org/article/MED/42958408",
  "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": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2705|Cardiac Fibrosis and Remodeling"
    ]
  ],
  "openalex": "W7224261717",
  "pdf_url": "https://europepmc.org/articles/PMC13721419?pdf=render",
  "pmcid": "PMC13721419",
  "pmid": "42958408",
  "published": "2026-10-29",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/bbgwyr30nhb7e.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:36Z",
      "native_id": "MED:42958408",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42958408"
    },
    {
      "first_seen": "2026-11-03T12:22:07Z",
      "native_id": "PMC13721419",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s13020-026-01562-2"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2705|Cardiac Fibrosis and Remodeling",
      "subfield": "cardiovascular"
    }
  ],
  "title": "Caffeic acid mitigates myocardial fibrosis via suppressing MAPKs/CREB-mediated inflammation in myocardial ischemia-reperfusion injury mice.",
  "title_text": "Caffeic acid mitigates myocardial fibrosis via suppressing MAPKs/CREB-mediated inflammation in myocardial ischemia-reperfusion injury mice.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-03T12:22:07Z",
  "url": "https://research.draconitic.com/paper/bbgwyr30nhb7e",
  "venue": "Chinese medicine",
  "versions": []
}