Suppression of type Ii collagen-induced arthritis by a new isocoumarin, NM-3
Agata, N.; Hirano, S.; Abe, C.; Nakashima, T.; Tsuchiya, A.; Kumagai, H.; Isshiki, K.; Yoshioka, T.; Ishizuka, M.; Takeuchi, T.
Research Communications in Molecular Pathology and Pharmacology 108(5-6): 297-309
2000
ISSN/ISBN: 1078-0297 PMID: 11958283 Document Number: 517093
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.