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More MS news articles for November 2002

Inhibition of LPS-induced p42/44 MAP kinase activation and iNOS/NO synthesis by parthenolide in rat primary microglial cells

Journal of Neuroimmunology, Vol. 132 (1-2) (2002) pp. 18-24
Bernd L. Fiebich a, Klaus Lieb a, Stefanie Engels a and Michael Heinrich b
a Department of Psychiatry and Psychotherapy, University of Freiburg Medical School, D-79104 Freiburg, Germany
b Centre for Pharmacognosy and Phytotherapy, School of Pharmacy, University of London, London, UK
Received 21 February 2002; received in revised form 17 July 2002; accepted 7 August 2002

Nitric oxide (NO) has been implicated in the etiopathology of central nervous system (CNS) diseases such as multiple sclerosis (MS).

Inhibition of NO synthesis has been proposed to be a possible mechanism of action of relevance in the treatment of multiple sclerosis and migraine.

Here, we investigated the effect of parthenolide on inducible NO synthase (iNOS) synthesis and NO release using primary rat microglia.

We found parthenolide to be an inhibitor of iNOS/NO synthesis.

Investigating the molecular mechanisms by which parthenolide prevents iNOS/NO synthesis, we found that parthenolide inhibits the activation of p42/44 mitogen-activated protein kinase (MAPK), but not IkBalpha (IkBa) degradation or nuclear factor-kappaB (NF-kB) p65 activation.

The data suggest that parthenolide might have a potential in the treatment of CNS diseases where NO is part of the pathophysiology.