Astragaloside IV mitigates mitochondrial damage and neurological symptoms in rats with cervical spondylotic myelopathy by inhibiting IL-17/TRAF6/NF-κB pathway.

Astragaloside IV (AS-IV) exhibits pharmacological effects like antioxidant, anti-inflammatory, and neuroprotective properties. Interleukin (IL)-17 and the tumor necrosis factor receptor-associated factor 6/nuclear factor-κB (TRAF6/NF-κB) pathway are closely associated with nerve injury, but whether AS-IV improves cervical spondylotic myelopathy (CSM)-related nerve injury through this pathway remains unclear. The aim of this study is to investigate whether AS-IV ameliorates nerve injury in CSM rats by regulating the IL-17/TRAF6/NF-κB axis. Primary spinal cord neurons were obtained from newborn rats, and neuronal injury was induced using lipopolysaccharide (LPS). The optimal concentration of AS-IV was determined by Cell Counting Kit-8 assay. Inflammatory cytokines, neuronal apoptosis, and mitochondrial function were detected by ELISA, Western Blot, flow cytometry, and fluorescence staining. The CSM rat model was constructed, and the motor function and pathological damage of spinal cord tissue were evaluated by behavioral score and pathological staining. The pathway-related proteins levels were assessed using Western Blot, and mitochondrial morphology in spinal cord tissue was viewed through transmission electron microscopy. LPS reduced neuronal viability, ATP production, and mitochondrial membrane potential levels and promoted apoptosis and pro-inflammatory factor secretion. AS-IV treatment reversed the above effects. IL-17 was highly expressed in LPS-induced neurons. IL-17 antibody inhibited TRAF6/NF-κB signaling pathway and reduced LPS-induced neuronal damage. AS-IV downregulated IL-17, and TRAF6 overexpression reversed the pathway inhibition of AS-IV, while silencing TRAF6 has the opposite effect. In vivo AS-IV improved behavioral score in CSM rats, restored lower limb electrophysiological potentials, mitigated pathological spinal cord damage, inhibited the IL-17/TRAF6/NF-κB pathway, preserved mitochondrial morphology, increased surviving neurons, reduced apoptosis, and promoted axon regeneration. AS-IV effectively improves mitochondrial dysfunction and associated damage in neurons by inhibiting IL-17 to hinder the TRAF6/NF-κB axis, thereby alleviating neurological symptoms in CSM rats.