Development of novel anti-inflammation and anti-rheumatism drugs

一氧化氮（Nitric oxide，NO）在多种生理过程中发挥重要作用，而诱导型一氧化氮合成酶（inducible NO synthase，iNOS）在感染性休克、炎症和自身免疫性疾病中起重要作用。苯醌能显著抑制LPS和IFN-γ激活的大鼠C6胶质细胞NO的产生。苯醌的抑制作用可能不是简单的氧化还原机制，因为它的二电子还原形式氢醌也强烈地抑制NO的产生。特别令人感兴趣的是，维生素K3通过相同的刺激显著增加NO的产生。机制研究表明，维生素K3通过增加NF-κ B的入核而增强iNOS基因的表达。尽管它们的化学结构简单，但维生素K3和苯醌对iNOS基因表达具有相反的作用。这些事实为合理设计基于选择性抑制iNOS活性的新型抗炎、抗风湿药物提供了有用的信息。

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.