ShenQiWan alleviates chondrocyte pyroptosis in knee osteoarthritis by inhibiting the NF-κB/NLRP3 signaling pathway.

OBJECTIVES

Knee osteoarthritis (KOA) is a progressive degenerative condition prevalent in older adults. ShenQiWan (SQW) has shown notable clinical efficacy in treating KOA. However, the role and mechanism of SQW in KOA are still poorly understood.

METHODS

Here, a destabilization medial meniscus (DMM)-induced KOA mouse model and LPS-induced chondrocytes were established to evaluate the protective effect of SQW in treating KOA. The impact of SQW on KOA cartilage and subchondral bone was assessed via micro-CT, histological examination, and immunohistochemical analysis. Simultaneously, LPS-stimulated KOA chondrocytes were treated with SQW to assess the proliferation, apoptosis, and inflammatory responses via CCK-8, ELISA, flow cytometry, RT-qPCR, and western Blot. NLRP3 overexpression was performed in chondrocytes to explore the role of SQW-mediated serum on the apoptosis and inflammation in LPS-induced chondrocytes by regulating the NF-κB/NLRP3 pathway.

RESULTS

SQW effectively improved gait and reduced pain-related behaviors in KOA mice. Micro-CT and histological analyses revealed that SQW alleviated subchondral bone loss and cartilage destruction, improved joint pathology. Molecular analyses revealed that SQW inhibited chondrocyte apoptosis and reduced the inflammatory response. Mechanistically, SQW down-regulated the expression of NLRP3 inflammasome-related proteins and inhibited the phosphorylation of NF-κB pathway components. In vitro, SQW protected LPS-induced chondrocytes from injury, improving viability and reducing apoptosis, while NLRP3 overexpression reversed these effects, confirming SQW acts via the NLRP3/NF-κB pathway.

CONCLUSIONS

SQW effectively reduces KOA symptoms by blocking the NF-κB/NLRP3 pathway, thereby lessening cartilage damage, inflammation, and cell death, while improving mobility and pain responses, highlighting its potential as a therapeutic agent for KOA.