Betulinic Acid Promotes Motor Function Recovery After Spinal Cord Injury by Inhibiting Apoptosis Through Myc/NF-κB...

Spinal cord injury (SCI) imposes a remarkable burden on affected cases and their families, while current treatment options remain insufficient. This study aimed to identify and validate the molecular targets, signaling pathways, and mechanisms by which Betulinic acid (BA) exerts its therapeutic effects on SCI, providing new directions for clinical intervention. In vivo, Kunming mice underwent behavioral tests, Nissl staining, and Hematoxylin-eosin staining to evaluate motor function recovery and determine the expression levels of relevant biomarkers. Bioinformatics analyses were employed to investigate the genes involved in the SCI-BA interaction, elucidating key signaling pathways, followed by molecular docking of potential target genes. In vitro, lipopolysaccharide was used to induce a secondary SCI condition in cultured astrocytes, enabling the evaluation of BA's effects on inflammatory and apoptotic responses. The results demonstrated that BA could significantly promote motor function recovery and reduce the expression levels of inflammation-related cytokines, including IL-1β, IL-6, and TNF-α, in SCI mice. Through bioinformatics analysis, Myc was identified as a key target of BA in SCI, and NF-κB and apoptosis pathways could be implicated in its mechanism of action. Both in vitro and in vivo experiments confirmed that BA could target Myc to modulate the inflammatory response in astrocytes, reducing the activation of RELA and MAPK14. In conclusion, these findings indicate that BA attenuates neuroinflammation and apoptosis via Myc and the NF-κB signaling pathway, thereby promoting functional recovery following SCI.