Mediators of Inflammation-Induced Bone Damage in Arthritis and Their Control by Herbal Products
ETHNOPHARMACOLOGICAL RELEVANCE Morus bombycis Koidzumi is widely distributed in Asia. In Korea, it has been used in traditional medicine because of its apparent anti-inflammatory, antioxidant, and hepatoprotective properties. AIM OF THE STUDY Although the extract of Morus bombycis Koidzumi (MB) has long since been used as a traditional anti-inflammatory medicine in Korea, its effect on arthritis remains unknown. We aimed to investigate the anti-arthritis activity of MB and the mechanism underlying it. MATERIALS AND METHODS The anti-arthritis activity of MB was assessed by using mouse models of type II collagen-induced arthritis (CIA). The clinical arthritis index and histopathological changes were evaluated in mice. Reverse transcriptase-polymerase chain reaction (RT-PCR), electrophoretic mobility shift assay (EMSA), and other biologic approaches were used for measuring the effect of MB on arthritis and understanding the underlying mechanism. RESULTS MB significantly decreased the clinical arthritis index in CIA mice; this was confirmed by examining histological changes in joints. Infiltration of immune cells, synovial hyperplasia, cartilage destruction, and bone erosion in the hind paw were largely suppressed by MB. The mRNA levels of matrix metalloproteinase (MMP)-1/MMP-3, inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6), and chemokines (macrophage inflammatory protein (MIP)-1, monocyte chemoattractant protein (MCP)-1, RANTES) were significantly suppressed by MB in a dose-dependent manner. The number of osteoclasts in the hind tibia was also significantly decreased. With regard to the mechanism, MB suppressed the activation of nuclear factor (NF)-κB and activator protein (AP)-1 in CIA mice. CONCLUSIONS MB produced an anti-arthritis effect in CIA mice by inhibiting the production of critical inflammatory mediators and osteoclasts through the downregulation of NF-κB and AP-1.