{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:00:13Z","timestamp":1790830813434,"version":"4.1.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>Astragalus membranaceus<\/jats:italic>\n                      , has neuroprotective and immunomodulatory effects, but its influence on Tregs and CD86\/CD206-associated microglial phenotypic responses remains unclear.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:sup>+<\/jats:sup>\n                      CD25\n                      <jats:sup>+<\/jats:sup>\n                      FOXP3\n                      <jats:sup>+<\/jats:sup>\n                      regulatory populations and additionally analyzed CD4\n                      <jats:sup>+<\/jats:sup>\n                      FOXP3\n                      <jats:sup>+<\/jats:sup>\n                      populations in the spleen and cervical lymph nodes, together with CD86\n                      <jats:sup>+<\/jats:sup>\n                      \/CD206\n                      <jats:sup>+<\/jats:sup>\n                      phenotypic responses within the CD11b\n                      <jats:sup>+<\/jats:sup>\n                      CD45^low\/int population in brain tissue. Immunofluorescence evaluated brain CD3\n                      <jats:sup>+<\/jats:sup>\n                      FOXP3\n                      <jats:sup>+<\/jats:sup>\n                      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                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      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-\u03b1 and increased IL-10 and TGF-\u03b2 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\n                      <jats:sup>+<\/jats:sup>\n                      FOXP3\n                      <jats:sup>+<\/jats:sup>\n                      signals in brain tissue. It also reduced CD86\n                      <jats:sup>+<\/jats:sup>\n                      -associated and increased CD206\n                      <jats:sup>+<\/jats:sup>\n                      -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                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1939189","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:45:39Z","timestamp":1790829939000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"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"],"prefix":"10.3389","volume":"17","author":[{"given":"Hengtong","family":"An","sequence":"first","affiliation":[{"name":"Hebei University of Chinese Medicine","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhan","family":"Guo","sequence":"additional","affiliation":[{"name":"Hebei University of Chinese 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