Vinpocetine ameliorates bone erosion and joint inflammation in rheumatoid arthritis via suppression of NLRP3 inflammasome

Rheumatoid arthritis (RA) is an autoimmune disease characterized by persistent synovial hyperplasia, cartilage degradation, and bone erosion. Vinpocetine (VIN), a semisynthetic derivative of the alkaloid vincamine, exhibits anti-inflammatory effects. However, the effect of VIN on NLRP3-mediated inflammation in RA remains unclear. In the collagen-induced arthritis (CIA) mouse model, treatment with vinpocetine (VIN) at doses of 5 and 10 mg/kg significantly alleviated characteristic symptoms of rheumatoid arthritis in CIA mice, including joint swelling, reduced grip strength, and mechanical hypersensitivity. Histopathological features of rheumatoid arthritis, such as bone erosion, cartilage destruction, and synovial hyperplasia, were also markedly improved in the CIA + VIN groups. In addition, the mRNA and protein expression levels of RA-associated inflammatory cytokines were significantly elevated in the CIA group but were markedly reduced in both CIA + VIN groups. Notably, VIN significantly suppressed the expression of NLRP3 inflammasome-related factors, including NLRP3, IL-1β, and IL-18, in CIA mice. Furthermore, VIN suppressed NLRP3 expression and inhibited osteoclastogenesis in bone marrow-derived macrophages (BMDMs). This study demonstrates that VIN mitigates structural damage in vivo and reduces joint inflammation by suppressing NLRP3 inflammasome activation in both in vivo and in vitro models, supporting its potential as a therapeutic candidate for rheumatoid arthritis.