Neferine reduces synovial inflammation and cardiac complications in a collagen-induced arthritis mouse model via inhibiting NF-κB/NLRP3 inflammasome axis

Abstract

For the treatment of rheumatoid arthritis (RA), there are limited options for drugs with fewer side effects. Neferine possesses anti-inflammatory, anti-fibrotic, and cardioprotective properties, but its effectiveness in the treatment of RA remains unclear. Our study aimed to explore the impact of neferine administration on ankle joint inflammation and cardiac complications of collagen-induced arthritis (CIA) mice. The CIA model was introduced in male DBA/1 mice via subcutaneous injection of Type II collagen (CII) into the tail. We found that neferine alleviated ankle joint inflammation, cartilage erosion, and bone destruction, as well as reduced the levels of IL-6, TNF-α, IL-1β, and IL-18 in the serum of CIA mice. Furthermore, neferine reduced the expression of synovial damage markers (RANKL, MMP-3, and MMP-13) in the ankle joints of CIA mice. Mechanistically, neferine lowered the levels of NF-κB pathway-related molecules such as p-IκBα, p-p65, and nuclear p65 in the synovial tissue of CIA mice. Simultaneously, neferine reversed the upregulation of NLRP3, ASC, and cleaved-caspase-1 levels in the synovial tissue of CIA mice. Additionally, our results showed that neferine reduced the contents of myocardial injury markers (cTnI, CK-MB, and LDH), alleviated myocardial fibrosis, decreased expression of α-SMA and Collagen I, as well as mitigated the activation of fibrosis-related TGF-β/Smad signaling. In summary, our study demonstrates that neferine attenuates chondral and synovial inflammation in a CIA mouse model by inhibiting the activation of the NF-κB/NLRP3 inflammasome, and neferine has a protective effect on the hearts of CIA mice.