{
  "abstract": "Background: Intracerebral hemorrhage (ICH) causes mechanical damage and cerebral edema. Annexin A2, expressed in endothelial cells, regulates cerebral edema, but its mechanisms in ICH remain unclear. Methods: A mouse ICH model was established using collagenase VII-S. We measured Annexin A2 expression, transcytosis, and blood–brain barrier (BBB) permeability. AAV was used to specifically knock down Annexin A2 in cerebrovascular endothelial cells. Protein interactions were identified by co-immunoprecipitation and label-free LC-MS. Ginsenoside Rh2 was tested for effects on protein binding (biolayer interferometry and competition assays) and on neurological/motor function, BBB integrity, and transcytosis. Results: ICH increased Annexin A2 expression, transcytosis, and BBB permeability. Annexin A2 knockdown worsened neurological deficits and motor function, increased BBB permeability, exacerbated tight junction disruption, but significantly reduced transcytosis. Six cytoskeletal proteins, Alpha-actinin-4, Actin-related protein 2, Actin alpha skeletal muscle, Actin cytoplasmic 1, Actin cytoplasmic 2, and Myosin-9, interacted with Annexin A2. Rh2 reduced binding affinity between Annexin A2 and these proteins, specifically inhibiting Annexin A2–Alpha-actinin-4 binding. Rh2 treatment improved neurological and motor function, reversed BBB disruption and tight junction damage, and suppressed transcytosis without altering Annexin A2 expression. Conclusion: Annexin A2 knockdown inhibited transcytosis but disrupted tight junctions and aggravated edema. In contrast, Rh2 inhibited transcytosis and exerts potential protective effect tight junctions, which may suggest a trend toward alleviation of cerebral edema to a certain extent. Selectively targeting Annexin A2-mediated transcytosis may be a promising therapy for ICH.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathology and Pathophysiology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.",
    "Department of Physiology, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.",
    "Research and Innovation Center, College of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.",
    "Department of Public Health, School of Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xu Han"
    },
    {
      "affs": [
        0
      ],
      "name": "Chu Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Qianlin Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Haixia You"
    },
    {
      "affs": [
        2
      ],
      "name": "Feiyan Chen"
    },
    {
      "affs": [
        2
      ],
      "name": "Cuihua Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Qi Yao"
    },
    {
      "affs": [
        3
      ],
      "name": "Dongqing Yang"
    },
    {
      "affs": [
        1
      ],
      "name": "Lin Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Zhu Zhu",
      "orcid": "0000-0003-1022-7113"
    },
    {
      "affs": [
        0
      ],
      "name": "Yunan Zhao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fty5vb25mmwqz.bib",
  "cited_by": 0,
  "doi": "10.1016/j.jgr.2026.101148",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S1226845326001740",
  "id": "fty5vb25mmwqz",
  "issns": [
    "1226-8453",
    "2093-4947"
  ],
  "landing_url": "https://doi.org/10.1016/j.jgr.2026.101148",
  "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"
    ],
    [
      "lcc",
      "QK1-989"
    ],
    [
      "openalex",
      "2808|Barrier Structure and Function Studies"
    ]
  ],
  "openalex": "W7204586876",
  "pdf_url": "https://europepmc.org/articles/PMC13711444?pdf=render",
  "pmcid": "PMC13711444",
  "pmid": "42948594",
  "published": "2026-08-28",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/fty5vb25mmwqz.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:43:38Z",
      "native_id": "f610bd1483b84c69b1e17c11a803a0e5",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.jgr.2026.101148"
    },
    {
      "first_seen": "2026-10-31T00:20:35Z",
      "native_id": "MED:42948594",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42948594"
    },
    {
      "first_seen": "2026-10-31T12:22:13Z",
      "native_id": "PMC13711444",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.jgr.2026.101148"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2808|Barrier Structure and Function Studies",
      "subfield": "neurology"
    }
  ],
  "title": "Ginsenoside Rh2, a putative functional modulator of Annexin A2, attenuates post-hemorrhagic stroke cerebral edema via inhibiting vesicular transcytosis",
  "title_text": "Ginsenoside Rh2, a putative functional modulator of Annexin A2, attenuates post-hemorrhagic stroke cerebral edema via inhibiting vesicular transcytosis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:13Z",
  "url": "https://research.draconitic.com/paper/fty5vb25mmwqz",
  "venue": "Journal of Ginseng Research",
  "versions": []
}