Anti-inflammatory effects of aucubin in cellular and animal models of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. It is known that aucubin (AU) exerts anti-inflammatory activity, but its effects and mechanisms in RA are unclear. This study investigated the anti-inflammatory effects and mechanisms of AU in vivo and in vitro. Human fibroblast-like synoviocyte cells from patients with RA (HFLS-RA), RAW264.7 cells, and MC3T3-E1 cells were used to evaluate the effects of AU on migration, invasion, apoptosis, osteoclast differentiation and production. Immunofluorescence was used to observe nuclear translocation of nuclear factor (NF)-Kappa B, the double luciferase reporter gene method was used to observe NF-Kappa B-p65 activity in AU-treated MC3T3-E1 cells. RT-qPCR was used to measure expression of bone metabolism and inflammation-related genes, and western blot was used to measure bone metabolism and NF-Kappa B protein expression levels. Collagen-induced arthritis (CIA) rat model was used for pharmacodynamics study. Arthritis indexes were measured in the ankle and knee, histological staining and Micro-computed tomography were performed on the ankle joints. Also, inflammatory factor gene expression and the levels of NF-Kappa B-related proteins were detected as in vitro. AU effectively inhibited HFLS-RA cell migration and invasion, promoted apoptosis, and inhibited RAW264.7 cell differentiation into osteoclasts, as well as inhibited NF-Kappa B-p65 activity in MC3T3-E1 cells. Notably, AU significantly reduced the gene expression levels of three cell-related inflammatory factors and bone metabolism factors, effectively inhibited the expression of p-I Kappa Kappa alpha beta, p-I Kappa B alpha, and p-p65 proteins. In vivo, AU relieved joint inflammation, reduced related inflammatory factors, and inhibited NF-Kappa B signaling. It could be used to treat RA-related synovial inflammation and bone destruction through the NF-Kappa B pathway. [CLC Number] R965 [Document code] A [Article ID] 2095-6975(2022)06-0458-15

Automated summary

In this study, the researchers investigated the anti-inflammatory effects and mechanisms of aucubin (AU) in rheumatoid arthritis (RA). They found that AU effectively inhibited cell migration and invasion, promoted apoptosis, and inhibited osteoclast differentiation. In addition, AU reduced the expression of inflammatory and bone metabolism-related genes and inhibited the NF-Kappa B signaling pathway. The results suggest that AU could be potentially used to treat synovial inflammation and bone destruction in RA.