Psoralen remodels the articular cartilage microenvironment by pharmacologically regulating the Nrf2 pathway in osteoarthritis treatment

Osteoarthritis (OA) is a common degenerative joint disease featuring extracellular matrix degradation and apoptosis in the inflammatory microenvironment. Psoralea, a traditional Chinese herb derived from the dried and ripe fruits of the leguminous plant Psoralea corylifolia , possesses anti-inflammatory and antioxidant properties relying on the expression upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2). Psoralen, a compound derived from Psoralea, can be well applied to the treatment of various diseases, while researches have not fully explored its therapeutic effect for OA. Our study aimed to conduct in vivo and in vitro experiments to investigate such effect. According to In vitro experiments, psoralen inhibited interleukin-6-induced chondrocyte inflammation and matrix metalloproteinase 13 production, meanwhile promoting aggrecan and type II collagen to be produced. Mechanistically, psoralen activated the Keap1/ Nrf2/ARE signaling pathway to enhance the antioxidant capacity of chondrocytes. Furthermore, in vivo experiments demonstrated the protective effect of psoralen against OA pathogenesis triggered by destabilized medial meniscus. Collectively, psoralen is considered as a potential candidate specific to OA treatment.