Bergapten protects chondrocytes against sodium nitroprusside-induced dedifferentiation and apoptosis through NF-κB and p38 signaling pathway.

Bergapten (BG), a furanocoumarin compound, has demonstrated diverse pharmacological properties, including the reduction of oxidative stress and inflammation in osteoarthritic chondrocytes. However, the mechanisms underlying BG's effects on chondrocyte differentiation and proliferation remain incompletely understood. This study aimed to elucidate BG's role in chondrocyte differentiation, proliferation, and inflammation prevention using in vitro and in vivo osteoarthritis (OA) models. An OA model was established by treating rabbit primary chondrocytes with sodium nitroprusside (SNP) to induce apoptosis and inflammation. BG treatment significantly upregulated chondrogenic differentiation markers, including type II collagen, SOX9, and aggrecan, and histological staining revealed increased proteoglycan accumulation in OA-induced cells treated with BG. Importantly, BG exhibited pronounced anti-inflammatory effects by modulating the NF-κB pathway: it increased IκBα expression and reduced cyclooxygenase-2 (COX-2) and p50 expression, thereby preventing inflammation in chondrocytes. BG also activated p38 kinase signaling, suggesting its contribution to Chondroprotective effects. Flow cytometry demonstrated that BG reduced SNP-induced apoptosis from 22 to 4%. Western blot analysis confirmed that BG downregulated apoptotic proteins p53 and BAX while upregulating the anti-apoptotic protein Bcl-2. In vivo validation using a zebrafish model showed that BG rescued SNP-induced craniofacial cartilage structural defects. These findings provide novel insights into BG's pharmacological role in promoting chondrocyte differentiation and survival, as well as preventing inflammation, by modulating key inflammatory pathways, apoptotic proteins, and chondrogenic markers. Given its clinical potential, BG may hold promise as a therapeutic agent for OA treatment.