Neuroprotective potential of the natural polyphenol Procyanidin B2 in spinal cord injury: a comprehensive study utilizing machine learning, network pharmacology, and

Background: The secondary injury cascade following spinal cord injury (SCI) drives severe inflammation and tissue destruction. Although the natural polyphenol Procyanidin B2 (PCB2) has well-documented neuroprotective properties, its specific therapeutic efficacy in SCI, as well as its precise therapeutic targets and immunomodulatory mechanisms, remain unclear. Methods: We applied an integrated Results: Network pharmacology initially yielded 59 shared targets, with functional enrichment pointing to PCB2's broad involvement in Toll-like receptor and p53 signaling, as well as tissue remodeling. This suggests its potential for multi-target anti-inflammatory and anti-apoptotic intervention. Machine learning algorithms then pinpointed Caspase-1 (CASP1) as the central regulatory node. Single-cell RNA sequencing showed that CASP1 expression surges specifically within macrophages and microglia following injury. Molecular docking supported a robust interaction (-7.2 kcal/mol) between PCB2 and the active pocket of CASP1. In our rat model, administering PCB2 notably hastened the return of bladder control and increased BBB locomotor scores. Histology confirmed that treated animals had smaller lesion volumes, better myelin integrity, and less inflammatory cell infiltration. At the molecular level, PCB2 significantly suppresses CASP1 expression, thereby blunting secondary damage. Conclusion: PCB2 demonstrates significant neuroprotective effects in SCI. Its mechanism primarily involves targeting