Development of novel anti-inflammation and anti-rheumatism drugs

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Nitric oxide (NO) plays an important role in diverse physiological processes, while induction of inducible NO synthease (iNOS) by various stimuli is responsible for pathogenesis of septic shock, and some inflammatory and auto immune diseases. Benzoquinone significantly inhibited NO production in rat C6-glia cell activated by LPS and IFN-γ. Inhibitory effect of benzoquinone might not simply be resulted from redox mechanism, because its two-electron reduced form, hydroquinone also strongly impaired NO production. Of special interest is it that vitamin K3 dramatically increases production of NO by the same stimuli. Mechanistic studies showed that vitamin K3 potentiates the expression of iNOS gene through increase of nuclear entry of NF-kB. In spite of their simple chemical structures, vitamin K3 and benzoquinone have contrary effects on iNOS gene expression. These facts would give useful information on rational design of an new anti-inflammatory and anti-rhymatism drug based on selective inhibition of iNOS activity.