Suppressive Effect of Dai-bofu-to on Collagen-Induced Arthritis

Abstract

Dai-bofu-to (DBT) is a traditional Japanese herbal medicine (Kampo medicine) used for the treatment of rheumatoid arthritis (RA). In the present study, to establish the usefulness of DBT, we examined the effect of DBT on collagen-induced arthritis (CIA). DBT (1.72 g/kg/d) significantly reduced the severity of arthritis throughout the experiment and significantly delayed the onset of arthritis. The induction of CIA decreased T cells and increased B cells in popliteal lymph nodes close to the affected joints, while the treatment of CIA with DBT counteracted the changes in T and B cells. In pX transgenic mice as a spontaneously developed arthritis model, a decrease in T cells and increase in B cells in popliteal lymph nodes were observed, as compared to BALB/c mice, the littermates of pX transgenic mice. In contrast, DBT returned the cell number of T and B cells to the level of BALB/c mice. As osteoclastogenesis is regulated by some T cell cytokines and osteotropic factors, we examined the effect of DBT on the receptor activator of NF-kappa B (RANK), RANK ligand (RANKL), osteoprotegerin (OPG) and M-CSF mRNAs, which were induced by arthritis induction. Although DBT had no effect on RNAK or RANKL mRNA levels, DBT stimulated an increase in OPG mRNA levels and suppressed an increase in M-CSF mRNA level. These results suggest that DBT may possess an anti-osteoclastogenetic effect, which is brought by reducing the ratio of RANKL/OPG and by decreasing M-CSF mRNA levels. In conclusion, immunomodulatory and anti-osteoclastogenetic effects might be involved in the suppression of arthritis by DBT.