Exploring the Mechanistic Role of Bushen Huoxue Decoction in Treating Intervertebral Disc Degeneration Through Efferocytosis Regulation

BACKGROUND: Bushen Huoxue (BSHX) decoction is effective against intervertebral disc degeneration (IVDD) and osteoarthritis, but its mechanism remains unclear. This study investigates its potential role in regulating efferocytosis in IVDD. METHODS: BSHX decoction, prepared from Eucommia ulmoides, Psoralea corylifolia, Achyranthes bidentata, Salvia miltiorrhiza, Clematis chinensis, and Chaenomeles speciosa, was extracted, concentrated, and analyzed by LC-MS/MS to identify active ingredients. Swiss TargetPrediction analysis predicted all targets. The PPI network was constructed using STRING 12.0 and CytoNCA in Cytoscape, followed by GO and KEGG enrichment analyses. Three publicly available datasets (GSE70362, GSE124272, GSE150408) were analyzed for differential gene expression in IVDD, with efferocytosis-related genes retrieved from GeneCards and KEGG, and candidate targets identified by intersecting PPI network core targets with efferocytosis-related differentially expressed genes (EFRDEGs). A network pharmacology model was then constructed, followed by molecular docking, molecular dynamics simulations, and pharmacokinetic properties. RESULTS: A total of 77 active ingredients and 298 targets were identified, with ELANE, MPO, and RXRA selected as candidate targets through bioinformatics analysis. GO and KEGG analyses highlighted their roles in immune regulation, inflammation, apoptosis, and tissue repair. Network analysis suggests that these compounds regulate multiple pathways, providing a mechanism for BSHX decoction to alleviate IVDD by modulating efferocytosis. Molecular docking showed strong binding affinity (binding energy < -8.0 kcal/mol) of tanshinone II A, pinoresinol diglucoside, and psoralidin with ELANE, MPO, and RXRA. Molecular dynamics simulation of the MPO-pinoresinol diglucoside complex confirmed its stability, and we revealed that pinoresinol diglucoside possesses favorable pharmacokinetic properties and safety characteristics. CONCLUSION: BSHX decoction may exert therapeutic effects on IVDD by targeting ELANE, MPO, and RXRA to regulate multiple pathways involved in efferocytosis. These findings offer valuable insights into the underlying mechanisms of BSHX decoction in the treatment of IVDD, providing a solid theoretical basis for the clinical application of traditional Chinese medicine.