Asperosaponin VI alleviates intervertebral disc degeneration by suppressing nucleus pulposus cell pyroptosis through modulation of the NF-κB/NLRP3 signaling pathway

Asperosaponin VI (ASA VI), a key bioactive compound derived from Dipsacus asper Wall., demonstrates significant pharmacological potential and is increasingly considered a promising therapeutic candidate. However, its precise role and underlying mechanisms in intervertebral disc degeneration (IDD) remain poorly understood. Given the growing evidence linking pyroptosis-induced inflammation to IDD pathogenesis, this study explored the regulatory effects of ASA VI in this context. Utilizing gene expression data from the Gene Expression Omnibus (GEO) database (GSE124272 and GSE34095), integrative analyses were performed, including protein-protein interaction (PPI) networks, Gene Ontology (GO), and KEGG pathway enrichment. The effects of ASA VI on cell viability, apoptosis, senescence, and cytokine secretion were evaluated in IL-1β-stimulated nucleus pulposus (NP) cells. Mechanistic insights were obtained through RNA sequencing, quantitative real-time PCR (qPCR), Western blot, and immunofluorescence, focusing on extracellular matrix (ECM) remodeling and the NF-κB/NLRP3 signaling pathway. In vivo efficacy was assessed in rat models of IDD, with analyses conducted via magnetic resonance imaging (MRI), micro-computed tomography (micro-CT), histological staining, and immunohistochemistry. ASA VI enhanced NP cell viability, inhibited IL-1β-induced apoptosis, senescence, and inflammatory cytokine production, while restoring ECM integrity and reducing NF-κB activation and pyroptosis markers. These effects were reversed upon pharmacological inhibition of NF-κB. ASA VI suppresses NF-κB and pyroptosis-related markers, promotes ECM remodeling, and delays IDD progression in vivo. Overall, these findings indicate that ASA VI alleviates IDD, potentially by inhibiting NF-κB-associated pyroptosis and promoting ECM homeostasis, positioning it as a promising therapeutic candidate for IDD.