Eriocitrin Mitigates Osteoarthritis Development by Suppressing Chondrocyte Inflammation and ECM Degradation via Nrf2/HO-1/NF-κB Pathways

Osteoarthritis (OA) is a chronic degenerative disorder of the joints, distinguished by ongoing damage and depletion of articular cartilage, synovial membrane inflammation, and extracellular matrix (ECM) degradation. Oxidative stress and chronic inflammation are central to OA progression, contributing to chondrocyte dysfunction, ECM degradation, and oxidative damage. Eriocitrin (Eri), a naturally derived flavonoid possessing substantial free-radical-scavenging and inflammation-modulating properties, has shown therapeutic potential; nevertheless, its specific function in OA remains ambiguous. In this study, we investigated the impact of Eri on interleukin-1β (IL-1β)-induced inflammation in murine chondrocytes and assessed its therapeutic efficacy in a murine OA model. Using network pharmacology, we identified 52 potential targets of Eri in OA. Molecular docking analysis revealed strong binding affinity between Eri and two critical regulators: nuclear factor erythroid 2-related factor 2 (Nrf2) and p65. Further experimental validation demonstrated that Eri activated the Nrf2 and heme oxygenase-1 (HO-1) pathway to enhance antioxidant defenses, while simultaneously inhibited the nuclear factor kappa B (NF-κB) pathway to reduce inflammation. Specifically, Eri suppressed IL-1β-induced inflammatory reactions in chondrocytes, reduced the secretion of pro-inflammatory cytokines, and inhibited ECM degradation, thereby suppressing the progression of OA. In vivo, Eri significantly slowed cartilage degeneration, simultaneously mitigated chondrocyte inflammation and ECM breakdown in OA mice. Together, these findings indicate that Eri mitigates OA progression by targeting both oxidative stress and inflammation through the Nrf2/HO-1 and NF-κB pathways. This study provides a mechanistic basis for further exploration of Eri as a potential therapeutic agent for OA.