Methyl isoeugenol attenuates inflammation and oxidative stress in osteoarthritis via repressing NF-κB/NLRP3 and JAK2/STAT3 pathways

Osteoarthritis (OA) is considered the most common chronic joint disease. With the aging population and the increasing incidence of obesity, the incidence of OA has increased. This study aimed to investigate the role and mechanism of methyl isoeugenol (MIE) in OA. Differentially expressed genes and enrichment analysis of DEGs of the GEO dataset (GSE55235) showed that these genes were predominantly linked to rheumatoid arthritis, osteoclast differentiation, and the NF-κB signaling pathway. The targets of MIE were predicted on TCMS, Swiss Target Prediction, PharmMapper, and the Similarity Ensemble Approach (SEA). Molecular docking was conducted to predict the binding relationship between MIE and core OA targets. JAK2, JUN, SYK, HCK, and CXCL12 were potential targets of MIE in OA. An in vivo OA model was established through destabilization of the medial meniscus (DMM), and IL-1β-stimulated CHON-001 chondrocytes, followed by MIE administration. The results confirmed that MIE dampened matrix loss and apoptosis in the knee cartilage tissue of the OA mouse model and mitigated apoptosis and extracellular matrix degradation in CHON-001 cells. MIE suppressed the activation of “M1” macrophages and restrained the JAK2/STAT3 and NF-κB/NLRP3/ASC/Caspase−1 pathways. In conclusion, the results of this study indicate that MIE protects against OA through the inhibition of the NF-κB/NLRP3 and JAK2/STAT3 pathways.