| Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes progressive joint destruction, deformity, disability, and premature death. A multitude of different pathways contributes to the pathogenesis of RA, and this situation is necessarily reflected in a rather poor efficacy of current therapeutic modalities. With respect to therapy of RA, the drug should rapidly control inflammation, halt the progressive joint destruction and be safe to use over an extended period. The current agents can generally control the symptom, such as pain and swelling, but in the long term are difficult to prevent the progressive joint destruction and have multiple side-effects. Seeking novel strategies and exploring new drugs are thus a permanent challenge for pharmacological research.Herbal medicine is a growing area of immuno-regulation. TongBiLing (TBL) is formulated by 15 kinds of traditional Chinese medicines on the basic of decoction of Cinnamomi, Paeoniae Alba and Anemarrhenae. It has the function of clearing away heatevil and wetness-evil, nourishing Yin and activating Yang, activating blood circulation and dissipating blood stasis, promoting blood circulation and acesodyne. TBL has long been used for the treatment of RA in China and Japan. Marked efficacy of TBL was demonstrated in several long-term clinical trials in China without any significant side effects. Our previous data have indicated TBL could significantly decrease serum anti-CII antibody titers, suppress chronic inflammation and improve joint and bone destruction in CIA mice. It also could restore the abnormal functions (i.e, IL-1 P > TNF-a production) of synoviocytes to normal levels, obviously suppress the proliferation of fibroblast, and significantly decrease the expression levels of IL~-1 $ , TNF- a mRNA of synoviocytes. However, the short-term and long-term therapeutical effects have not been evaluation yet. So, in our present study, we will further evaluate the therapeutical effects, especially in the suppression of joint distruction using mouse CIA model.Type II collagen-induced arthritis (CIA) in DBA/1 mouse has been proven to be a valuable model of RA, in that it incorporates many of the cell-mediated and humoral immunity characteristics found in human RA. Since its first description, CIA has been widely used as a powerful tool to study immune responses in arthritis, analyze genetic susceptibility factors, unravel inflammatory pathways, and explore the therapeutic effects of potential antirheumatic drugs. Although not identical to RA, CIA is characterized bypronounced synovitis and erosions of cartilage and bone.Methotrexate (MIX) is a disease-modifying anti-rheumatic drug (DMARD), frequently used for treatment of patients with RA for its predominant immuno-suppressive efficacy. In present study, MTX, a classical SAARD, served as positive control, we not only evaluated the short-term (2 weeks) therapeutic effects of TBL, but also confirmed the long- term (8 weeks) therapeutic effects of TBL, specially the suppressed effect of TBL on joint destruction of CIA. The result showed that short-term TBL treatment has no effect on CIA symptom, but can adjust immune disorder, such as decrease the concentration of anti-CII antibody, IL-1 P . Histological analysis also showed that synovium erosion and inflammatory infiltration were improved. TBL provided protection against effects of CIA including chronic inflammatory, cartilage and bone destruction in vivo after treated for 8 weeks. Comparison of clinical and radiological scores of CIA model demonstrated that treatment with high dose of TBL for 8 weeks resulted in marked attenuation. Those indicated that TBL not only ameliorated CIA symptom but also modified disease of CIA. However, at lower dose, TBL lacks of effect on the joint and bone destruction despite the decrease of clinical scores.The short-term therapeutic effect of MTX is not satisfied, although it could reduce significantly the leveal of anti-CII antibody in sera of CIA mice. However, after treated with MTX 8 weeks, symptom...
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