Targeting p38 MAPK signaling pathway:  Quercetin as a novel therapy for TMJ synovitis

Temporomandibular joint (TMJ) synovitis is a chronic inflammatory condition prevalent in temporoman-dibular disorders, characterized by synovial inflammation and bone degradation. Quercetin, a natural flavonoid with diverse bioactive properties, is investigated for its potential in ameliorating TMJ synovitis by targeting the p38 MAPK pathway. Using network pharmacology and <i>in vitro</i> and <i>in vivo</i> models, the effects of quercetin on synoviocytes and inflammatory responses were evaluated. Results showed quercetin's significant inhibition of synoviocyte proliferation, promotion of apoptosis and reduction of inflammatory cytokines. Moreover, quercetin demonstrated stability in binding to critical targets like MAPK14 and led to downregulation of phosphorylated p38 MAPK and JNK. <i>In vivo</i>, quercetin improved synovial tissue architecture and mitigated bone destruction. Mechanistic studies confirmed the dependency of effects of quercetin on the p38 MAPK pathway, supported by functional experiments using pathway agonists and inhibitors. The present study underscored the potential of quercetin in treating TMJ synovitis by modulating inflammatory signaling, promoting cell apoptosis and preserving bone integrity, thereby offering novel insights into therapeutic strategies for TMJ‑related synovitis.