The object of this study is to observe the effects of platycodin D, a saponin purified from Platycodi Radix, on mice collagen-induced arthritis (CIA). A daily dose of 200, 100, and 50？mg/kg platycodin D was administered orally to male DBA/1J mice for 40 days after initial collagen immunization. To ascertain the effects administering the collagen booster, CIA-related features (including body weight, poly-arthritis, knee and paw thickness, and paw weight increase) was measured from histopathological changes in the spleen, left popliteal lymph node, third digit, and the knee joint regions. CIA-related bone and cartilage damage improved significantly in the platycodin D-administered CIA mice. Additionally, myeloperoxidase (MPO) levels in the paw were reduced in platycodin D-treated CIA mice compared to CIA control groups. The level of malondialdehyde (MDA), an indicator of oxidative stress, decreased in a dose-dependent manner in the platycodin D group. Finally, the production of IL-6 and TNF-α, involved in rheumatoid arthritis pathogenesis, was suppressed by treatment with platycodin D. Taken together, these results suggest that platycodin D is a promising new effective antirheumatoid arthritis agent, exerting anti-inflammatory, antioxidative and immunomodulatory effects in CIA mice. 1. Introduction Rheumatoid arthritis (RA) is a common human autoimmune disease characterized by chronic inflammation of the synovial membranes with concomitant destruction of cartilage and bone. Although the etiology and pathogenesis of RA are not yet understood, it has been suggested that abnormalities of cytokines, such as interleukin (IL)-1, IL-6, and TNF-α, play an important role in the pathogenesis [1]. In addition, the current view of the cytokine network in rheumatoid joints supports the notion that TNF-α activates a cytokine cascade characterized by the simultaneous production of proinflammatory cytokines such as IL-1 and IL-6 and of anti-inflammatory cytokines such as IL-10, IL-1Ra, and soluble TNF receptor [2]. In epidemiological studies, oxidative damage to proteins, lipids, DNA, cartilage, and extracellular collagen has been demonstrated in patients with RA [3] and moreover has demonstrated an inverse correlation between the dietary intake of antioxidants and the incidence of RA [4]. Lipid peroxidation markers such as serum malondialdehyde (MDA) and urine isoprostane are reported to be elevated in collagen-induced arthritis (CIA) compared with those in controls [5, 6]. As above concepts for pathogenesis of RA, clinical application with TNF-α-neutralizing antibody
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