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

IF 4.8 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-03-17 DOI:10.1016/j.intimp.2025.114401

Rongbao Yan , Ye Yuan , Ce Shi , Yang Li , Yang Li , Wenbo Wang , Lei Yang

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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.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.