Astragaloside IV Mitigates Subarachnoid Hemorrhage-Induced Brain Injury via Regulating Microglial Polarization and Neuroinflammation Mediated by cGAS/STING Pathway

  • Chin J Integr Med. 2026 Apr 16. doi: 10.1007/s11655-026-3954-x.
Wen-Chao Ding  1  2  3 ,  Yong-Jun Wang  1  2  3  4 ,  Lu Cao  4 ,  Wen-Hao Ding  1  2  3 ,  Shu-Qing Yu  1  2  3 ,  Wen-Jing Zheng  1  2  3 ,  Yue-Cheng Cui  1  2  3 ,  Lin-Mei Wang  5 ,  Shao-Hua Chen  6 ,  Ning Li  1  2  3 ,  Hao Xu  1  2  3 ,  Qian-Qian Liang  1  2  3 ,  Jin-Man Chen  7  8  9
Affiliations
  • 1. Institute of Spine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
  • 2. Spine Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
  • 3. Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education (Shanghai University of Traditional Chinese Medicine), Shanghai, 201203, China.
  • 4. School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 5. Department of Anatomy, School of Basic Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 6. Department of Education and Research, Shanghai Changning Tianshan Traditional Chinese Medicine Hospital, Shanghai, 200051, China.
  • 7. Institute of Spine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. [email protected].
  • 8. Spine Institute, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China. [email protected].
  • 9. Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education (Shanghai University of Traditional Chinese Medicine), Shanghai, 201203, China. [email protected].
PMID: 41989498 DOI: 10.1007/s11655-026-3954-x
Abstract

Objective: To investigate the effects of astragaloside IV (AS-IV) on subarachnoid hemorrhage (SAH)-related brain injury and explore the underlying mechanisms.

Methods: The effects of related signaling pathways on SAH were analyzed through stimulator of interferon gene (STING) knockout and RNA Sequencing (RNA-seq) in mice. In vitro, mouse BV2 microglial cell line was stimulated with hemin to establish a model mimicking SAH. AS-IV was administered after SAH. Neurological deficits and the therapeutic effects of AS-IV in mice were assessed using modified Garcia scores. ELISA and Western blot were employed to measure the expressions of inflammatory factors and the Cyclic GMP-AMP Synthase (cGAS)/STING signaling pathway both in vivo and in vitro, respectively. TUNEL staining was used to evaluate neuronal Apoptosis, Fluoro-Jade C (FJC) staining for neuronal degeneration, immunofluorescence for microglial activation and polarization, and flow cytometry for myeloid cell changes in peripheral blood.

Results: The knockout of STING alleviated early brain injury following SAH (P<0.01). RNA-seq revealed the activation of the cGAS/STING and NF-κB related pathways following SAH. In vitro, hemin elevated cGAS-STING and inflammatory factor levels in microglial cells, while AS-IV significantly inhibited these effects (P<0.05 or P<0.01). SAH mice showed reduced neurological scores, obvious systemic inflammation, increased neuronal Apoptosis and degeneration, with elevated cGAS-STING pathway and inflammatory factors in brain tissue (P<0.05 or P<0.01). AS-IV suppressed these effects and improved microglial activation and morphology (P<0.05 or P<0.01).

Conclusions: In the early stage of brain injury following SAH, AS-IV regulates microglial polarization through the cGAS/STING pathway, thus improving neurological outcomes and alleviating neuroinflammation. AS-IV may be an effective therapeutic agent for the pathology of neuroinflammation following SAH.

Keywords
astragaloside IV; early brain injury; microglia; neuroinflammation; subarachnoid hemorrhage.
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