Naringin Alleviates Knee Osteoarthritis by Targeting TNF-α and PTGS2: An Integrated Network Pharmacology, Molecular Simulation, and Experimental Validation Study

Knee osteoarthritis (KOA) is a chronic degenerative joint disorder driven largely by persistent inflammation and progressive cartilage damage. Naringin, a bioactive flavonoid abundant in citrus fruits, has shown potential anti-inflammatory effects; however, its molecular mechanisms in KOA remain unclear. In this study, an integrated approach combining network pharmacology, molecular docking, molecular dynamics (MD) simulations, and in vitro experiments was employed to investigate the anti-inflammatory effects of naringin in KOA. Network pharmacology analysis identified 59 potential KOA-related targets of naringin, among which TNF, PTGS2, TP53, CASP3, and PPARG were recognized as core targets. Functional enrichment indicated these targets were primarily associated with inflammation- and apoptosis-related pathways, especially the TNF and IL-17 signaling pathways. Molecular docking and MD simulations revealed strong binding affinity and stable interactions between naringin and the key inflammatory mediators TNF-α and PTGS2. In an IL-1β-stimulated C28/I2 human chondrocyte model, naringin dose-dependently improved cell viability and significantly suppressed TNF-α and PTGS2 expression at both mRNA and protein levels. These findings provide mechanistic evidence that naringin alleviates KOA-associated chondrocyte inflammation by modulating key inflammatory mediators, supporting its potential as an anti-inflammatory therapeutic candidate for KOA.