{
  "abstract": "Background: Ischemic stroke triggers persistent neuroinflammation, microglial activation, and peripheral immune changes that aggravate secondary brain injury. Astragaloside IV (AS-IV), a major bioactive constituent of Astragalus membranaceus , has neuroprotective and immunomodulatory effects, but its influence on Tregs and CD86/CD206-associated microglial phenotypic responses remains unclear.\n\nAim: This study investigated whether AS-IV attenuates post-ischemic neuroinflammation in association with Treg-related immune responses, PI3K/AKT signaling alterations, and CD86/CD206-associated brain myeloid phenotypic responses.\n\nMaterials and methods: A mouse middle cerebral artery occlusion (MCAO) model was established using the intraluminal filament method. Neurological deficits, infarct volume, and histopathological injury were evaluated after AS-IV treatment. Western blotting and ELISA were used to assess inflammatory cytokines and PI3K/AKT-associated signaling in ischemic brain tissue. Transcriptomic analysis identified AS-IV-related biological processes and pathways. Flow cytometry quantified CD4 ⁺ CD25 ⁺ FOXP3 ⁺ regulatory populations and additionally analyzed CD4 ⁺ FOXP3 ⁺ populations in the spleen and cervical lymph nodes, together with CD86 ⁺ /CD206 ⁺ phenotypic responses within the CD11b ⁺ CD45^low/int population in brain tissue. Immunofluorescence evaluated brain CD3 ⁺ FOXP3 ⁺ signals and Iba1/CD86 or Iba1/CD206 double-positive signals. Anti-CD25 intervention was used to evaluate the involvement of Treg-related immune responses in AS-IV-associated effects.\n\nResults: AS-IV reduced infarct volume, showed a trend toward improvement in neurological deficit scores, and alleviated histopathological injury after MCAO. It decreased IL-6 and TNF-α and increased IL-10 and TGF-β in ischemic brain tissue. Transcriptomic analysis identified changes associated with the PI3K/AKT signaling pathway and immune regulatory processes, while western blotting showed increased p-PI3K/PI3K and p-AKT/AKT ratios after AS-IV treatment. AS-IV increased Treg proportions in the spleen and cervical lymph nodes and increased CD3 ⁺ FOXP3 ⁺ signals in brain tissue. It also reduced CD86 ⁺ -associated and increased CD206 ⁺ -associated brain myeloid phenotypic responses. Anti-CD25 partially attenuated AS-IV-associated improvements in neurological and brain injury outcomes, as well as its effects on inflammatory cytokines and brain myeloid phenotypic responses.\n\nConclusion: AS-IV attenuated post-ischemic neuroinflammation in association with Treg-related immune responses and PI3K/AKT-associated signaling alterations, accompanied by changes in CD86/CD206-associated brain myeloid phenotypic responses. These findings support AS-IV as a potential neuroimmunomodulatory intervention for ischemic stroke.",
  "abstract_shown": true,
  "affiliations": [
    "Hebei University of Chinese Medicine , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hengtong An"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuhan Guo"
    },
    {
      "affs": [
        0
      ],
      "name": "Shaoze Yang"
    },
    {
      "affs": [
        0
      ],
      "name": "Tianci Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaowen Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Zejun Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Yitong Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ruotong Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xiaohong Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Weijuan Gao"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/atvnf5hczkg2r.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1939189",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668508/?tool=EBI",
  "id": "atvnf5hczkg2r",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13668508",
  "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": [
    [
      "openalex",
      "2808|Neuroinflammation and Neurodegeneration Mechanisms"
    ]
  ],
  "openalex": "W7215099511",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13668508/pdf/?tool=EBI",
  "pmcid": "PMC13668508",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/atvnf5hczkg2r.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:18Z",
      "native_id": "PMC:PMC13668508",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13668508"
    },
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1939189",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1939189/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2808|Neuroinflammation and Neurodegeneration Mechanisms",
      "subfield": "neurology"
    }
  ],
  "title": "Astragaloside IV attenuates post-ischemic neuroinflammation associated with Treg-related regulation of CD86/CD206-associated brain myeloid phenotypic responses and PI3K/AKT signaling alterations",
  "title_text": "Astragaloside IV attenuates post-ischemic neuroinflammation associated with Treg-related regulation of CD86/CD206-associated brain myeloid phenotypic responses and PI3K/AKT signaling alterations",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:15Z",
  "url": "https://research.draconitic.com/paper/atvnf5hczkg2r",
  "venue": "Frontiers in immunology",
  "versions": []
}