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

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.