Fuzi decoction ameliorates intervertebral disc degeneration through ferroptosis modulation by suppressing NF-κB...

Intervertebral disc degeneration (IVDD) is a complex condition that necessitates the development of novel therapeutic strategies. The objective of this study was to investigate the therapeutic potential of Fuzi decoction (FZD) in the treatment of IVDD by examining its bioactive components, target genes, molecular interactions, pathways, and therapeutic efficacy.

Bioactive ingredients with an oral bioavailability (OB) of ≥ 30 % and drug likeness (DL) of ≥ 0.18 were identified using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Target genes associated with IVDD were retrieved from various databases, and a Venn diagram was employed to determine the common targets between IVDD and FZD. Subsequent network analyses, including ingredient-target-disease networks and protein-protein interaction (PPI) networks, were constructed. Functional enrichment analyses, such as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), were conducted to delineate the biological processes, pathways, and potential mechanisms. Molecular docking was utilized to validate the interactions between FZD ingredients and target genes. In vitro assays using nucleus pulposus cells (NPCs) evaluated the effects of FZD-containing serum (FCS) on extracellular matrix (ECM) degradation, ferroptosis, and NF-κB pathway modulation. Additionally, rat models were used to confirm the therapeutic effects of FZD on IVDD.

FZD was found to contain 77 bioactive ingredients and 108 related targets, with 101 common targets identified between IVDD and FZD. Network analyses pinpointed key ingredients and targets, with a particular focus on PTGS2 and IL1B as central to IVDD. Enrichment analyses revealed pathways related to reactive oxygen species and NF-κB signaling. Molecular docking confirmed robust interactions between core ingredients and target proteins. Pharmacological findings were substantiated by in vitro and in vivo experiments, demonstrating that FCS alleviated IL-1β-induced ECM degradation and ferroptosis by inhibiting the NF-κB pathway in NPCs.

FZD demonstrates efficacy in alleviating IVDD by regulating ECM degradation and ferroptosis through the suppression of the NF-κB signaling pathway. These findings suggest that FZD may be a promising therapeutic agent for the treatment of IVDD, offering insights into its multifaceted mechanisms and molecular interactions for potential clinical application.