Astragaloside IV attenuates post-ischemic neuroinflammation associated with Treg-related regulation of CD86/CD206-associated brain myeloid phenotypic responses and PI3K/AKT signaling alterations
- 1Hebei University of Chinese Medicine , ,
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.
Aim: 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.
Materials 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.
Results: 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.
Conclusion: 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.
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BibTeX
@article{an2026astragaloside,
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}},
author = {Hengtong An and Shuhan Guo and Shaoze Yang and Tianci Zhang and Xiaowen Li and Zejun Ma and Yitong Wang and Ruotong Wang and Xiaohong Zhou and Weijuan Gao},
journal = {Frontiers in immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1939189},
url = {https://europepmc.org/article/PMC/PMC13668508},
note = {CC BY},
}
RIS
TY - JOUR
TI - Astragaloside IV attenuates post-ischemic neuroinflammation associated with Treg-related regulation of CD86/CD206-associated brain myeloid phenotypic responses and PI3K/AKT signaling alterations
AU - Hengtong An
AU - Shuhan Guo
AU - Shaoze Yang
AU - Tianci Zhang
AU - Xiaowen Li
AU - Zejun Ma
AU - Yitong Wang
AU - Ruotong Wang
AU - Xiaohong Zhou
AU - Weijuan Gao
PY - 2026
DA - 2026/10/01
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1939189
UR - https://europepmc.org/article/PMC/PMC13668508
AB - 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. Aim: 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. Materials 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. Results: 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. Conclusion: 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.
SN - 1664-3224
ER -