BC-1 improves collagen-induced arthritis in mice by modulating IgD and BCR-NF-κB signalling pathway of B cells

Rheumatoid arthritis (RA) is an autoimmune disease lacking effective treatment drugs. Beesia calthaefolia Ulbr. widely distributes in the southwest and northwest of China. Its rhizomes are used as traditional Chinese medicine (TCM) for the treatment of rheumatoid arthritis, dysentery, colds, sore throats, and headaches. (20S*, 24R*)-epoxy-9,19-cyclolanostane-3β,12β,16β,25-tetraol-3-O-β-D-xylopyranoside (BC-1) was a key anti-inflammatory saponin isolated from Beesia calthaefolia. However, the specific anti-RA mechanism of BC-1 has not yet been fully elucidated. In this study, an RA model was established by collagen in DBA1 mice, the immune cells in spleen of mice were analyzed using CyTOF. As a result, BC-1 significantly relieved arthritis severity and decreased the AI score of CIA mice with no significant impact on bodyweight. Additionally, BC-1 can also reduce inflammatory, osteoclast formation, cartilage damage, and bone damage in ankle joint, decreased the serum levels of TNF-α, IL-1β, IL-6, PGE₂ and COX-2 of CIA mice. According to the CyTOF assay, the ratio of B cells/immune cells and IgD levels in B cell markedly increased in CIA mice, which were relieved by BC-1. Furthermore, BC-1 significantly inhibited the activation of BCR-NF-κB signalling pathway of B cells. These findings suggested that BC-1 has the potential for RA treatment by inhibiting IgD and BCR-NF-κB signalling pathway.