Cinnamaldehyde Attenuates the Progression of Rheumatoid Arthritis through Down-Regulation of PI3K/AKT Signaling Pathway

Cinnamaldehyde (CA), as an active compound isolated from the bark ofCinnamomum cassia, has been reported to possess the anti-fungal, anti-bacterial, anti-inflammatory, anti-mutagenic, and anti-oxidant properties. However, the possible effects and underlying mechanisms of CA on rheumatoid arthritis (RA) have not been revealed yet. In the present study, we found that CA obviously improved the type II collagen-induced RA in rats, accompanied with decreasing pro-inflammatory factors, proliferation and metastasis. In addition, CA decreased the expression levels of TNF-alpha, IL-1 beta, and IL-6 in RA-FLSs. Besides, CA remarkably inhibited the proliferation, downregulated the EdU-positive cells, and promoted apoptosis of RA-FLSs by CCK-8, EdU and flow cytometry analysis. Moreover, the results of wound healing, transwell migration and invasion assays showed that CA inhibited the migration and invasion of RA-FLSs. Further, western blot experiment showed CA inhibited the activation of PI3K/AKT signaling pathway in RA-FLSs. Finally, 740Y-P, the PI3K/AKT signaling pathway activator, could reverse the effects of CA on the proliferation and metastasis in RA-FLSs. In conclusion, we confirmed that CA exhibited potential therapeutic properties against RAviasuppressing proliferation and metastasis of RA-FLSs by blockage of PI3K/AKT signaling pathway. Therefore, our study provides evidence that CA may emerge as a therapeutic option for RA treatment.