The Therapeutic Potential of Pristimerin in Osteoarthritis: Mechanistic Insights from in vitro and in vivo Studies

Objective: Osteoarthritis (OA), a degenerative disease marked by cartilage erosion and synovial proliferation, has led to an increased interest in natural plant-based compounds to slow its progression. Pristimerin(Pri), a triterpenoid compound derived from Tripterygium wilfordii, has demonstrated anti-inflammatory and antioxidant characteristics. This study explores the protective effects of Pri on OA and its potential mechanisms. Methods: In this study, we examined the impact of Pri on the expression of inflammatory factors and extracellular matrix(ECM) degradation induced by IL-1(3 in chondrocyte experiments. Bioinformatics analysis was then performed to investigate the potential signaling pathways involved in Pri's protective effects. Finally, the efficacy of Pri in reducing cartilage degradation was further evaluated in a destabilization of the medial meniscus (DMM) mouse model. Results: Utilizing bioinformatics analysis and in vitro studies, it was revealed that Pri inhibits the activation of NF-kappa B and MAPK signaling pathways, leading to the reversal of upregulated MMP-13 (matrix metalloproteinases-13), iNOS (inducible nitric oxide synthase), and COX-2(cyclooxygenase-2) elicited by IL-1(3 stimulation, as well as the partial restoration of Collagen-II levels. Furthermore, in a DMM mouse model, the group treated with Pri exhibited reduced cartilage degradation and slowed OA progression compared to the modeling group. Conclusion: This research highlights Pri as a potential therapeutic agent for delaying OA progression.