In inflammation, bacterial products and proinflammatory cytokines induce the formation of large amounts of nitric oxide ( NO) by inducible nitric oxide synthase ( iNOS), and compounds that inhibit NO production have anti-inflammatory effects. In the present study, we systematically investigated the e. ects of 36 naturally occurring flavonoids and related compounds on NO production in macrophages exposed to an inflammatory stimulus ( lipopolysaccharide, LPS), and evaluated the mechanisms of action of the effective compounds. Flavone, the isoflavones daidzein and genistein, the flavonols isorhamnetin, kaempferol and quercetin, the flavanone naringenin, and the anthocyanin pelargonidin inhibited iNOS protein and mRNA expression and also NO production in a dose-dependent manner. All eight active compounds inhibited the activation of nuclear factor-kappa B ( NF-kappa B), which is a significant transcription factor for iNOS. Genistein, kaempferol, quercetin, and daidzein also inhibited the activation of the signal transducer and activator of transcription 1 ( STAT-1), another important transcription factor for iNOS. The present study characterises the e. ects and mechanisms of naturally occurring phenolic compounds on iNOS expression and NO production in activated macrophages. The results partially explain the pharmacological efficacy of flavonoids as anti-inflammatory compounds. Copyright c 2007 Mari Hamainen et al.
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Hämäläinen, M., Nieminen, R., Vuorela, P., Heinonen, M., & Moilanen, E. (2007). The Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-B activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-B activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators of Inflammation, 2007 (2007), art. 45673, 10 s. https://doi.org/10.1155/2007/45673