Attenuation of experimental autoimmune encephalomyelitis in C57 BL/6 mice by osthole, a natural coumarin

Osthole, a natural coumarin, is known to have a variety of pharmacological and biochemical uses and is considered to have potential therapeutic applications. Here we examined the effects of osthole on the central nervous system demyelination in experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis and its mechanism(s). C57 BL/6 mice immunized with myelin oligodendrocyte glycoprotein 35-55 amino acid peptide were treated with osthole at day 7 post immunization (7 p.i., subclinical periods, early osthole treatment) and day 13 p.i. (clinical periods, late osthole treatment) respectively and both therapies continued throughout the study. The content of nerve growth factor (NGF) and interferon gamma (IFN-gamma) in the sera and brain of mice in vivo as well as the splenocytes Culture supernatants in vitro were detected. The results showed that osthole retarded the disease process when the therapy was initiated at subclinical periods, attenuated the clinical severity of EAE mice when the therapy was initiated at both subclinical and clinical periods, ameliorated inflammation and demyelination and improved the outcomes of magnetic resonance imaging. In addition, osthole blocked the reduction of NGF and suppressed IFN-gamma increase in EAE mice. These results suggested that osthole might be a new pharmacological approach to treat multiple sclerosis. (C) 2009 Elsevier B.V. All rights reserved.