Astragaloside IV enhances autophagy to suppress endoplasmic reticulum stress and pyroptosis after spinal cord injury

  • Cell Signal. 2026 Sep:145:112571. doi: 10.1016/j.cellsig.2026.112571.
Zhichen Jiang  1 ,  Zhouwei Wu  1 ,  Yuchen Jin  2 ,  Keming Xu  2 ,  Weizhi Shu  1 ,  Yuzhe Wu  1 ,  Juntao Ying  1 ,  Junhao Wu  1 ,  Yibo Geng  1 ,  Chenglong Hong  1 ,  Jingwei Shi  1 ,  Chenggui Wang  1 ,  Kailiang Zhou  3 ,  Jianjun Qi  4 ,  Hui Xu  5
Affiliations
  • 1. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou 325027, China; The Second Clinical Medical College of Wenzhou Medical University, Wenzhou 325027, China.
  • 2. The Second Clinical Medical College of Wenzhou Medical University, Wenzhou 325027, China.
  • 3. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou 325027, China; The Second Clinical Medical College of Wenzhou Medical University, Wenzhou 325027, China. Electronic address: [email protected].
  • 4. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou 325027, China; Department of Laboratory Medicine, The First Affiliated Hospital of Wannan Medical University (Yijishan Hospital of Wannan Medical University), Wuhu 241001, China. Electronic address: [email protected].
  • 5. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China; Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou 325027, China; The Second Clinical Medical College of Wenzhou Medical University, Wenzhou 325027, China. Electronic address: [email protected].
PMID: 42086120 DOI: 10.1016/j.cellsig.2026.112571
Abstract

Spinal cord injury (SCI) is a devastating insult to the central nervous system that causes severe motor and sensory dysfunction; however, effective therapeutic strategies remain limited because the mechanisms underlying secondary injury are not fully understood. In this study, we investigated the therapeutic effects of the bioactive compound astragaloside IV (AST-IV) in a mouse model of SCI. Through functional, histological, and molecular analyses, we demonstrated that AST-IV treatment significantly improved neurological recovery after SCI. Mechanistically, AST-IV exerted neuroprotective effects through the activation of AMPK-mediated Autophagy and the enhancement of autophagic flux, thereby preserving mitochondrial homeostasis, attenuating endoplasmic reticulum stress-associated Apoptosis, and suppressing Pyroptosis. Importantly, pharmacological inhibition of Autophagy markedly attenuated the protective effects of AST-IV, indicating that the neuroprotective effect of AST-IV is mediated by Autophagy. Collectively, these findings reveal an autophagy-dependent mechanism underlying AST-IV-mediated neuroprotection and support the therapeutic potential of AST-IV for mitigating secondary injury after SCI.

Keywords
AST-IV; Autophagy; Endoplasmic reticulum stress; Pyroptosis; Spinal cord injury.
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