Latvian Institute of Organic Synthesis, Riga, Latvia.
Basic Clin Pharmacol Toxicol. 2010 Jun;106(6):461-6. doi: 10.1111/j.1742-7843.2009.00526.x. Epub 2010 Jan 18.
When administered as drugs or consumed as food components, polyphenolic compounds synthesized in plants interfere with intracellular signal transduction pathways, including pathways of nitric oxide synthase expression. However, effects of these compounds in vivo do not always correlate with nitric oxide synthase-inhibiting activities revealed in experiments with cultured cells. The initial goal of this work was to compare effects of flavonoids kaempferol and myricetin on inducible nitric oxide synthase mRNA and protein expression monitored by real-time RT-PCR and immunohistochemistry and to evaluate the impact of these effects on nitric oxide production in rat organs measured by means of electron paramagnetic resonance spectroscopy. Kaempferol and myricetin attenuated the lipopolysaccharide-induced outburst of inducible nitric oxide synthase gene expression; kaempferol also significantly decreased the lipopolysaccharide-induced outburst of inducible nitric oxide synthase protein expression in the liver. Myricetin decreased nitric oxide production in intact rat liver. Kaempferol did not decrease nitric oxide production neither in intact rats nor in the lipopolysaccharide-treated animals. Kaempferol even enhanced the lipopolysaccharide-induced increase of nitric oxide production in blood. Myricetin did not interfere with lipopolysaccharide effects. As both kaempferol and myricetin are known as inhibitors of inducible nitric oxide synthase expression, our results suggest that modifications of nitric oxide level in tissues by these compounds cannot be predicted from data about its effects on nitric oxide synthase expression or activity.
当作为药物或食物成分被摄入时，植物中合成的多酚化合物会干扰细胞内信号转导途径，包括一氧化氮合酶表达途径。然而，这些化合物在体内的作用并不总是与在培养细胞中进行的实验中揭示的一氧化氮合酶抑制活性相关。这项工作的最初目标是比较黄酮类化合物山奈酚和杨梅素对诱导型一氧化氮合酶 mRNA 和蛋白质表达的影响，这些影响通过实时 RT-PCR 和免疫组织化学监测，并评估这些影响对通过电子顺磁共振波谱法测量的大鼠器官中一氧化氮产生的影响。山奈酚和杨梅素减弱了脂多糖诱导的诱导型一氧化氮合酶基因表达的爆发；山奈酚还显著降低了肝脏中脂多糖诱导的诱导型一氧化氮合酶蛋白表达的爆发。杨梅素降低了完整大鼠肝脏中的一氧化氮产生。山奈酚既没有降低完整大鼠中也没有降低脂多糖处理动物中的一氧化氮产生。山奈酚甚至增强了血液中脂多糖诱导的一氧化氮产生的增加。杨梅素不干扰脂多糖的作用。由于山奈酚和杨梅素都被认为是诱导型一氧化氮合酶表达的抑制剂，我们的结果表明，这些化合物对组织中一氧化氮水平的修饰不能根据其对一氧化氮合酶表达或活性的影响的数据来预测。
