Pharmacological Network Analysis to Explore the Functions and Mechanisms Underlying the Effect of Quercetin from Achyranthis Bidentatae Radix on Intervertebral Disc Degeneration

Intervertebral disc degeneration (IDD) is a common multifactorial disorder in orthopedics and a leading cause of low-back pain. Achyranthis Bidentatae Radix (ABR) and its active components have been applied in clinical treatments for IDD. This study aimed to explore the therapeutic effects and the underlying mechanisms of ABR in treating IDD. Network pharmacology, RNA sequencing (RNA seq), molecular docking, and molecular dynamics simulation were employed to predict potential ABR targets for IDD treatment. An in vitro IDD model was established using IL-1β–treated nucleus pulposus cells (NPCs). To explore the biological processes and signaling pathways, we employed toluidine blue staining, β-Gal senescence staining, CCK-8 assay, TUNEL apoptosis assay, reactive oxygen species (ROS) detection, flow cytometry, RT-qPCR, and western blotting. Network pharmacology and RNA-seq confirmed 30 overlapping hub genes. Functional enrichment annotation showed their significant involvement in hypoxia, collagen biosynthetic, inflammatory response, angiogenesis, and PI3K-Akt signaling pathway. Protein-protein interaction (PPI) analysis, molecular docking and molecular dynamics simulations revealed that quercetin (QUE), a major active component of ABR, exhibits strong binding affinity to the core target NOS3 (eNOS). In vitro experiments demonstrated that QUE significantly improved NPCs viability and reduced oxidative stress, extracellular matrix (ECM) degradation, inflammatory responses, apoptosis, and cellular senescence induced by IL-1β. Furthermore, QUE inhibited phosphorylation of p-PI3K, p-Akt, and p-NOS3 in IDD progression. Our results suggest that QUE protects NPCs from IL-1β–induced injury by regulating NPC viability, oxidative stress, ECM degradation, inflammatory responses, apoptosis, and cellular senescence. The PI3K/Akt/eNOS signaling pathway may play a critical role in this process.