Abstract
This study aims to elucidate the biological effects of Baicalein (BA) on intervertebral disc degeneration (IDD) and the potential mechanisms involved. Network pharmacology analysis was performed to identify the core targets and signaling pathways responsible for the therapeutic effects of BA on IDD. In vitro validation was carried out using IL-1β-stimulated nucleus pulposus cells (NPCs). Cell viability, apoptosis, inflammatory cytokines (TNF-α, IL-6), extracellular matrix (ECM)-related molecules (MMP3, Aggrecan, Collagen II), and the phosphorylation of ERK and p38 were measured using CCK-8 assay, flow cytometry, qRT-PCR, ELISA and Western blot. Network pharmacology identified 80 common targets and highlighted the MAPK signaling pathway as a key mechanism. In vitro, BA (50 µmol/L) mitigated IL-1β-induced cytotoxicity in NPCs and promoted cell proliferation. BA significantly inhibited apoptosis by regulating the Bcl-2/Bax family and cleaved c-caspase-3. It also decreased the expression of TNF-α and IL-6, and reversed ECM homeostasis by modulating MMP-3, Aggrecan and Collagen II expression. Furthermore, BA treatment effectively suppressed IL-1β-induced phosphorylation of ERK and p38. Notably, the MAPK agonist anisomycin partially abolished the above protective phenotypes of BA and restored MAPK phosphorylation. BA alleviates apoptosis, inflammatory response and ECM degradation in NPCs, to retard IDD development mainly through inhibiting MAPK pathway activation, supporting the clinical translational potential of BA for IDD treatment.