Kanglexin attenuates spinal cord injury by modulating pyroptosis and polarization via the PKA/NF-κB signaling pathway

Abstract

Background

Neuroinflammation is essential for intricate pathophysiologic mechanisms after spinal cord injury (SCI). Increasing evidence suggests that anthraquinones possess anti-inflammatory properties in central nervous system (CNS) disorders. However, the effects of Kanglexin (Klx), a novel synthetic anthraquinone compound, on SCI remain unknown.

Methods

C57BL/6 mice were utilized to establish a contused SCI model to explore the in vivo neuroprotective and inflammatory modulatory effects of Klx. An inflammation model was also created in vitro using BV2 cells. Neuroprotective effects were assessed by evaluating motor function and neuropathologic alterations. Inflammation modulation was analyzed through markers of polarization and pyroptosis, with further mechanistic insights obtained via transcriptome sequencing.

Results

Klx facilitated the recovery of hindlimb locomotor function and improved neuronal survival after SCI. Both in vitro and in vivo assays revealed that Klx inhibited NLRP3 inflammasome-induced pyroptosis. In addition, Klx promoted the polarization of microglia from the proinflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Mechanistically, Klx enhanced PKA phosphorylation and suppressed NF-κB and IκBα phosphorylation, thereby reducing NF-κB nuclear translocation.

Conclusion

Klx demonstrated neuroprotective and inflammation-modulating effects on SCI, suggesting that it might offer a promising therapeutic alternative for SCI.