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• W2013904713 abstract "We investigated the mechanism of suppression of inducible nitric oxide synthase (iNOS) by two beta-carboline alkaloids isolated from Melia azedarach, 4,8-dimethoxy-1-vinyl-beta-carboline (compound 1, C-1) and 4-methoxy-1-vinyl-beta-carboline (compound 2, C-2). iNOS activity in a cell-free extract of lipopolysaccharide/interferon-gamma-stimulated RAW 264.7 cells was found to be markedly increased, and this increase was prevented by C-1 and C-2, accompanied by the parallel reduction in nitrite accumulation in culture medium. However, C-1 and C-2 had no further effect on the iNOS activity prepared from fully lipopolysaccharide/interferon-gamma-stimulated RAW 264.7 cells. Treatment with C-1 or C-2 decreased the levels of iNOS protein and mRNA in a concentration-dependent manner. In addition, prostaglandin E(2) production, cyclooxygenase-2 protein and DNA binding of nuclear factor-kappaB (NF-kappaB) in lipopolysaccharide-stimulated RAW 264.7 cells were reduced by these compounds. These results indicate that C-1 and C-2 primarily inhibit iNOS and cyclooxygenase-2 activities via the suppression of de novo synthesis of these two enzymes, and that the inhibition of iNOS expression may be associated with the inhibition of NF-kappaB activation. Taken together, the results suggest that suppression of iNOS and cyclooxygenase-2 induction by lipopolysaccharide is responsible for the anti-inflammatory activity of these alkaloids through selective inhibition of the expression of genes, which play important roles in inflammatory signaling pathways." @default.
• W2013904713 created "2016-06-24" @default.
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• W2013904713 date "2000-10-01" @default.
• W2013904713 modified "2023-10-16" @default.
• W2013904713 title "Suppression of inducible nitric oxide synthase expression in RAW 264.7 macrophages by two β-carboline alkaloids extracted from Melia azedarach" @default.
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• W2013904713 doi "https://doi.org/10.1016/s0014-2999(00)00680-4" @default.
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