Geniposide exerts protective effects on spinal cord injury in rats by inhibiting the IKKs/NF-κB signaling pathway

Background: Spinal cord injury (SCI) is a traumatic condition of the central nervous system , which can cause nerve injury and affect nerve regeneration, thus leading to severe dysfunction of motor and sensory pathways, and unfortunately these effects are irreversible. Inflammatory response constitutes one of the important mechanisms of spinal cord secondary injury. Geniposide (Gen) is reported to possess anti-inflammation and neuronal repair capacities. Objectives: To investigate the effect and mechanism of Gen on motor function and inflammatory response in SCI rats. Methods: Sprague-Dawley (SD) rats were randomly grouped, and the SCI model was established by Allen's method. The motor function of rats was evaluated by the Basso, Beattie, and Bresnahan (BBB) scale. The protective effect of Gen on the injured spinal cord tissues was evaluated by measuring the water content, myeloperoxidase (MPO) activity, and levels of tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and IL-6. Moreover, the protein level of the inflammation-related pathway was detected by spectrometry and Western blot assays. Results: Gen significantly promoted the recovery of SCI rats, decreased the edema of spinal cord tissues, reduced the area of cavity, increased the number of NF-200-positive neurons, as well as increased the number of horseradish peroxidase (HRP) retrograde tracing-positive neurons and regenerated axons with myelin sheath. Additionally, compared with the control group, the neutrophil infiltration, contents of TNF-alpha, IL-1 beta, and IL-6, the activity of inhibitor of nuclear factor kappa B kinase subunit beta (IKK beta) kinase, and protein levels of (nuclear factor kappa B) NF-Kappa B p65 and phosphorylated inhibitor of NF-kappa B (p-I-kappa B) in the Gen experimental group were significantly decreased. Conclusion: Gen effectively alleviated inflammatory response after SCI by inhibiting the IKKs/NF-kappa B signaling pathway and promoted the recovery of motor function and axon regeneration in rats. Significance: This study can provide novel insights for the early and effective intervention of SCI and confer basic data for the treatment of spinal cord secondary injury.