Salvianolic Acid B Enhances Motor Function Recovery after Spinal Cord Injury in Association with AKT/mTOR/HIF-1α Pathway Activation and Angiogenesis.

Spinal cord injury (SCI) is a devastating condition with limited treatment options. Salvianolic acid B (SalB), a natural compound from Salvia miltiorrhiza, shows therapeutic potential, but its mechanisms in SCI remain unclear. This study integrated network pharmacology and experimental validation to investigate the effects of SalB. We combined network pharmacology, molecular docking, and in vivo experiments using a rat SCI model, and applied the AKT inhibitor Capivasertib (AZD5363) for mechanistic verification. Network analysis identified 188 SalB-SCI common targets primarily in the AKT pathway, and molecular docking predicted strong binding between SalB and AKT1. In rats, SalB improved motor function, reduced tissue damage, and enhanced neuronal survival in association with activation of the AKT/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) axis and promoted angiogenesis, while these effects were reversed by AZD5363. Collectively, our findings demonstrate that SalB treatment is associated with activation of the AKT/mTOR/HIF-1α pathway and enhanced angiogenesis, which correlate with improved functional recovery after SCI. These results provide experimental evidence for the multi-target reparative mechanisms of SalB and highlight its promise as a therapeutic intervention for SCI.