2. Academic Validation
  3. Kanglexin attenuates spinal cord injury by modulating pyroptosis and polarization via the PKA/NF-κB signaling pathway

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

  • Int Immunopharmacol. 2025 Mar 17:153:114401. doi: 10.1016/j.intimp.2025.114401.
Rongbao Yan 1,  Ye Yuan 2,  Ce Shi 3,  Yang Li 4,  Yang Li 5,  Wenbo Wang 6,  Lei Yang 7
Affiliations

Affiliations

  • 1 Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, China; NHC Key Laboratory of Cell Transplantation, The First Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: 202201198@hrbmu.edu.cn.
  • 2 Department of Pharmacy (The University Key Laboratory of Drug Research, Heilongjiang Province), The Second Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: yuanye_hmu@126.com.
  • 3 NHC Key Laboratory of Cell Transplantation, The First Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: shice@hrbmu.edu.cn.
  • 4 Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China; NHC Key Laboratory of Etiology and Epidemiology, Harbin Medical University, Harbin, China; Joint Key Laboratory of Endemic Diseases(Harbin Medical University, Guizhou Medical University, Xi'an Jiaotong University), Harbin Medical University, Harbin Medical University, Harbin, China; Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin Medical University, Harbin, China; Key Laboratory of Etiology and Epidemiology, Education Bureau of Heilongjiang Province, Harbin Medical University, Harbin, China. Electronic address: yangli9295@hrbmu.edu.cn.
  • 5 NHC Key Laboratory of Cell Transplantation, The First Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: liyang0119@hrbmu.edu.cn.
  • 6 Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: 809435293@qq.com.
  • 7 Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, China; NHC Key Laboratory of Cell Transplantation, The First Affiliated Hospital of Harbin Medical University, Harbin, China; Key Laboratory of Hepatosplenic Surgery of Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China; State Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin Medical University, Harbin, China. Electronic address: yanglei@hrbmu.edu.cn.
PMID: 40101425 DOI: 10.1016/j.intimp.2025.114401
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.

Keywords

Inflammation; Kanglexin; Neuroprotection; Polarization; Pyroptosis; Spinal cord injury.

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