{
  "abstract": "Introduction: Chronic stress severely impairs physical and mental health and is a critical risk factor for cardiovascular diseases. Formononetin (FMN) has shown promising cardiovascular protective effects, yet its functional role and molecular mechanism in chronic stress-triggered arterial neointimal hyperplasia and concomitant mood disturbances remain poorly elucidated.\n\nMethods: Network pharmacology was used to predict the underlying mechanisms of FMN against cardiovascular disease-depression comorbidity. A dual mouse model recapitulating chronic stress and carotid artery injury was established for in vivo validation. Histological staining, behavioral tests, Western blotting, β -galactosidase staining, and in vitro VSMC assays were performed to assess the effects of FMN and the HDAC6 inhibitor TubA.\n\nResults: Network pharmacology identified 111 overlapping targets, with functional enrichment and molecular docking revealing that FMN primarily regulates inflammation, apoptosis, and autophagy via binding to core hub proteins including HDAC6, Bcl-2, and AKT1. In vivo , chronic stress aggravated arterial intimal hyperplasia and aortic senescence, and induced anxiety- and depression-like behaviors. FMN treatment notably improved emotional disorders, reduced HDAC6 expression, activated autophagy (increased LC3B/A ratio), inhibited apoptosis (elevated Bcl-2/Bax ratio), attenuated NLRP3 and IL-6 expression, and alleviated intimal thickening. The HDAC6 inhibitor TubA recapitulated the vascular protective effects of FMN.\n\nDiscussion: FMN attenuates chronic stress-induced vascular injury and emotional dysfunction via suppressing HDAC6 signaling to restore autophagy, inhibit inflammation, and reduce apoptosis. This study unveils the dual cardio-neuroprotective capacities of FMN and provides novel mechanistic insights for the treatment of chronic stress-related cardiocerebral comorbidities.",
  "abstract_shown": true,
  "affiliations": [
    "The School of Public Health, Guilin Medical University",
    "Key Cultivation Laboratory of Life Cycle Health Care Research",
    "Guangxi Key Laboratory of Environmental Exposures and Whole Life Cycle Health",
    "Department of Clinical Nutrition, Liuzhou Workers’ Hospital",
    "School of Artificial Intelligent Medicine, Guilin Medical University",
    "Department of Pediatrics, The First Affiliated Hospital of Guangxi Medical University",
    "Communicable Disease Control Branch, Qingdao Municipal Center for Disease Control and Prevention",
    "Department of Nutrition, Second People’s Hospital of Ya'an City",
    "School of Health and Hygiene, Beihai Health and Wellness Vocational College",
    "Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
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        0,
        1,
        2,
        3
      ],
      "name": "Shanqian Li"
    },
    {
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        0,
        1,
        2
      ],
      "name": "Wanhua Wu"
    },
    {
      "affs": [
        4
      ],
      "name": "Chaozhi Xu"
    },
    {
      "affs": [
        5
      ],
      "name": "Yue Huang"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Guixian Wu"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Hongyu Ding"
    },
    {
      "affs": [
        6
      ],
      "name": "Zongyi Zhang"
    },
    {
      "affs": [
        7
      ],
      "name": "Yulin Zhang"
    },
    {
      "affs": [
        8
      ],
      "name": "Meimei Zheng"
    },
    {
      "affs": [
        9
      ],
      "name": "Hongxian Wu"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Lina Hu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1m004f5s1hgbm.bib",
  "cited_by": 0,
  "doi": "10.3389/fcvm.2026.1865656",
  "fulltext_url": "https://europepmc.org/articles/PMC13683145",
  "id": "1m004f5s1hgbm",
  "issns": [
    "2297-055X"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fcvm.2026.1865656/full",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2403|Atherosclerosis and Cardiovascular Diseases"
    ]
  ],
  "openalex": "W7220850281",
  "pdf_url": "https://europepmc.org/articles/PMC13683145?pdf=render",
  "pmcid": "PMC13683145",
  "pmid": "42908797",
  "published": "2026-10-07",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/1m004f5s1hgbm.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:10Z",
      "native_id": "10.3389/fcvm.2026.1865656",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fcvm.2026.1865656/full"
    },
    {
      "first_seen": "2026-10-30T12:20:14Z",
      "native_id": "MED:42908797",
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  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2403|Atherosclerosis and Cardiovascular Diseases",
      "subfield": "immunology"
    }
  ],
  "title": "Formononetin relieves chronic stress-related neointimal hyperplasia in mice by regulating HDAC6",
  "title_text": "Formononetin relieves chronic stress-related neointimal hyperplasia in mice by regulating HDAC6",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:14Z",
  "url": "https://research.draconitic.com/paper/1m004f5s1hgbm",
  "venue": "Frontiers in Cardiovascular Medicine",
  "versions": []
}