Plumbagin relieves rheumatoid arthritis through nuclear factor kappa-B (NF-kappa B) pathway

This study aimed to explore the effects of plumbagin on rheumatoid arthritis (RA) and its mechanism. The RA cell model was simulated following the treatment of interleukin-1 beta (IL-1 beta). After the treatment of various concentrations of plumbagin, the impact of plumbagin on the cell viability was examined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazoliurn bromide (MTT) assay. The collagen-induced arthritis (CIA) model was established using the solution of bovine type II collagen. Hematoxylin-eosin staining was used to observe the changes of ankle joint tissue, while enzyme-linked immunosorbent assay and western blot were applied to detect the level of inflammatory cytokines. Plumbagin inhibited the viability of human fibroblast-like synoviocytes (HFLS) at the concentration of 1 similar to 3.5 mu M. The inhibitory effect of 1 mu M plumbagin on cell proliferation was similar to that of methotrexate, the drug used as the positive control. Plumbagin downregulated the levels of inflammatory cytokines and matrix metalloproteinases (MMPs) in IL-1 beta-treated HFLS, and suppressed the activation of IKB and nuclear factor kappa-B (NF-kappa B) as well as the entry of p65 into the nucleus. It was also demonstrated in animal experiments that plumbagin inhibited the activation of NE-KB pathway, down-regulated the levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and MMPs, and alleviated joint damage in CIA-modeled mice. Collectively speaking, plumbagin might down-regulate the levels of inflammatory cytokines and MMPs through inhibiting the activation of the NF-kappa B pathway, thereby attenuating RA-induced damage to cells and joints.

Automated summary

Plumbagin may attenuate RA-induced damage to cells and joints by down-regulating the levels of inflammatory cytokines and MMPs through inhibiting the activation of the NF-kappa B pathway.