Cinnamaldehyde-Mediated Suppression of MMP-13, COX-2, and IL-6 Through MAPK and NF-κB Signaling Inhibition in Chondrocytes and Synoviocytes Under Inflammatory Conditions

Inflammatory disorders encompass a range of conditions, including osteoarthritis (OA), characterized by the body's heightened immune response to diverse stimuli. OA is a prevalent degenerative joint disease characterized by the progressive deterioration of joint cartilage and subchondral bone, leading to pain, limited mobility, and physical disability. Synovitis, the inflammation of the synovial membrane, is increasingly recognized as a critical factor in OA pathogenesis and progression. This study evaluates the therapeutic potential of cinnamaldehyde (CA), a bioactive compound derived from cinnamon, on synovial and articular inflammation in OA. Given CA's established anti-inflammatory, antioxidant, and antibacterial properties, this research explores its specific impact on OA and synovitis. The cytotoxicity of CA was assessed using a CCK-8 assay in human IL-1β pretreated chondrocytes and synoviocytes, which serve as in vitro models of OA and synovitis. The study further examined the effects of CA on the expression of proinflammatory cytokines, including IL-6, COX-2, and TNF-α, utilizing multiple analytical techniques. Additionally, the production of matrix metalloproteinases (MMP-3 and MMP-13) and the activation of the NF-κB signaling pathway, particularly the phosphorylation of p65 (pp65), were investigated. The role of the NF-κB inhibitor 5HPP-33 and its downstream effects on gene expression, including COX-2 and IL-6, as well as the MAPK pathway components (p38, ERK, and JNK), were also explored. An MEK inhibitor (U0126) was employed to assess its downstream impact on COX-2 and IL-6 expressions. The results demonstrated that CA significantly inhibited the expression of proinflammatory cytokines and suppressed NF-κB activation in IL-1β pretreated chondrocytes and synoviocytes. These findings suggest that CA, in a dose-dependent manner, may serve as an effective therapeutic agent for preventing OA and synovitis, offering valuable insights into its potential role in managing synovial inflammation and OA.