The Open Bioactive Compounds Journal
2010, 3 : 12-17Published online 2010 August 20. DOI: 10.2174/1874847301003010012
Publisher ID: TOBCJ-3-12
RESEARCH ARTICLE
Cytokine-Modulatory Activity and Therapeutic Efficacy of 7-Amino-4-Methylcoumarin in Murine Collagen-Induced Arthritis
b Department of Pathology, Rinku General Medical Center, Izumisano, Osaka, 598-8577 Japan,
c Department of Virology, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
* Address correspondence to this author at Department of Biochemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, 1714-1 Yoshino, Nobeoka, Miyazaki 882-8508, Japan; Tel: +81-982-23-5574; Fax: +81-982-23-5684; E-mail: b2mk@phoenix.ac.jp
ABSTRACT
7-Amino-4-methylcoumarin (AMC) was previously shown to suppress pro-inflammatory cytokine production and prevent death in an endotoxic shock model in mice. In the present study, we investigated the effectiveness of AMC as a potential cytokine modulator in alleviating autoimmune diseases. We examined the efficacy and cytokine-modulatory activity of AMC in collagen-induced arthritis (CIA) in mice. Mice were immunized with type II collagen. AMC at 0, 3, or 30 mg/kg was administered orally to the immunized mice once daily for three weeks before and/or three times daily for two weeks after the onset of CIA. The development of arthritis of the paws and cytokine levels in serum were examined. AMC significantly reduced the incidence and severity of CIA prophylactically and therapeutically, and suppressed the rise of systemic interleukin-6 and interferon-γ (levels to the basal levels in the early phase of CIA. AMC also significantly suppressed the level of tumor necrosis factor-α in the severe phase of CIA. However, the levels of interleukin-10 and anti-collagen antibody were not affected by AMC. In the early phase of CIA, the suppression of interleukin-6 and interferon-γ (levels by AMC correlated with the amelioration of symptoms of CIA in a dose-dependent manner. AMC may inhibit the onset of cytokine-mediated disease rather than suppressing disease progression without toxicity or affecting anti-collagen antibody production. AMC was significantly effective against CIA in mice and confirmed to possess cytokine-modulatory activity in vivo. The results suggest that AMC is a potential therapeutic agent for autoimmune diseases.