Curculigoside Inhibits the Progression of Osteoarthritis via Regulating Nucleotide-Binding Oligomerization Domain-Like Receptor Containing Pyrin Domain 3

Abstract

This study aimed to explore the potential effects of curculigoside on NLRP3 expression and catabolic genes in osteoarthritis (OA) development. OA mouse models were generated by destabilizing the medial meniscus (DMM) and treated with curculigoside. Curculigoside treatment resulted in dose-dependent reductions in OARSI scores, with the 20 μg dose restoring scores to normal levels. Curculigoside increased mRNA and protein levels of iNOS and MMP9 induced by DMM surgery in a dose-dependent manner. Moreover, curculigoside downregulated the expression of NLRP3, NF-κB, and PKR at both mRNA and protein levels. Additionally, curculigoside reversed the effects of IL-1β on MMP-9, iNOS, and Col2A mRNA and protein levels in a dose-dependent manner, similar to the NLRP3 inhibitor MCC950. In vivo and in vitro results supported curculigoside’s potential to aid cartilage restoration in OA patients by blocking the NLRP3 pathway. These findings suggest curculigoside as a potential therapeutic option for OA, offering hope for improved public health outcomes related to this degenerative joint condition.