Mechanism of Duzhong Bushen Formula Regulating MAPK/AP-1 Pathway to Improve Lumbar Intervertebral Disc Degeneration: Evidencefrom Network Pharmacology and In Vivo Experiment in Rats

Introduction: This study aimed to investigate the therapeutic mechanism of Duzhong Bushen Formula (DBF) in ameliorating lumbar Intervertebral Disc Degeneration (IDD) via regulation of the MAPK/AP-1 pathway. Methods: Based on a circular puncture-induced rat model of IDD, network pharmacology and molecular docking analysis were employed to identify key therapeutic targets and pathways for DBF in treating IDD. In vivo validation of these targets was conducted via MRI, histopathology, ELISA, Western blot, and qPCR, with therapeutic efficacy further evaluated. Results: DBF administration significantly reduced inflammatory markers (CRP, IL-6, TNF-α), increased serum levels of Albumin (ALB) and Estrogen (E2), and downregulated key components of the MAPK/AP-1 pathway (p-p38, c-FOS, c-JUN). High-dose DBF demonstrated the most pronounced therapeutic effects. Discussion: The results suggest that DBF attenuates IDD by suppressing inflammatory responses and oxidative stress through modulation of the MAPK/AP-1 signaling axis. Conclusion: DBF may be a promising multi-target therapeutic agent for the treatment of IDD, particularly in cases involving kidney deficiency and blood stasis.