201. Suppression of type II collagen-induced arthritis by a new isocoumarin, NM-3
- Author
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N, Agata, S, Hirano, C, Abe, T, Nakashima, A, Tsuchiya, H, Kumagai, K, Isshiki, T, Yoshioka, M, Ishizuka, and T, Takeuchi
- Subjects
Male ,Foot ,Body Weight ,Organ Size ,Thymus Gland ,Carrageenan ,Arthritis, Experimental ,Rats ,Radiography ,Mice ,Isocoumarins ,Coumarins ,Mice, Inbred DBA ,Antirheumatic Agents ,Immunoglobulin G ,Animals ,Edema ,Collagen Type II ,Spleen - Abstract
The anti-arthritic effect of NM-3, a new isocoumarin, was examined using a type II collagen-induced arthritis model for human rheumatoid arthritis in DBA/1J mice. NM-3 by oral administration suppressed dose-dependently (2-20 mg/kg/day) not only macroscopic changes such as erythema and swelling of limbs but also histopathologic changes and radiographic changes such as bone lesions. The efficacy of NM-3 was greater than those of disease-modifying anti-rheumatoid drugs (DMARDs), auranofin (40 mg/kg/day) and bucillamine (10 mg/kg/day). NM-3 failed to suppress carageenan-induced edema and to inhibit the activities of inflammation-related enzymes including cyclooxygenase-1 and -2, 5-lipoxygenase and phospholipase A2, suggesting that the mode of anti-arthritic action of NM-3 may be different from those of non-steroidal anti-inflammatory agents (NSAIDs). Since NM-3 inhibits angiogenesis in a mouse dorsal air-sac model, the observed anti-arthritic effect of NM-3 might be partly attributed to the antiangiogenic activity. Thus, NM-3 is a potential orally active therapeutic agent for the treatment of human rheumatoid arthritis.
- Published
- 2002