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Beneficial effects of natural compounds are often attributed to modulation of NO production; however effects produced by plant extracts do not correlate with effects of purified components. The goal of our work was to study ability of flavonoids and indole-3-carbinol, as well as their combinations to modify NO production, iNOS gene and protein expression in rat tissues. Baicalein and luteolin decreased NO concentration in both intact and LPS-treated animals. Baicalein decreased iNOS gene expression. Luteolin decreased NO production in the liver and heart and number of iNOS-positive cells in the liver of LPS-treated animals. Combination of the two substances did not decrease the NO synthesis triggered by LPS, although it decreased iNOS gene expression. Quercetin decreased NO production in the heart, kidneys and blood of intact rats, but enhanced the LPS effect in testes, spleen and blood on NO production and iNOS protein expression in the liver. Indole-3-carbinol decreased NO concentration in the cerebellum, blood, lungs and skeletal muscles. The drug enhanced the LPS-triggered increase of NO production in all rat organs. It increased iNOS protein expression in intact liver; however it decreased the LPS-triggered outburst of the enzyme biosynthesis. Combination of indole3-carbinol with quercetin decreased NO production in LPS-treated animals however it slightly increased iNOS gene expression. Taken together our results suggest that modifications of NO level in tissues by a natural compound cannot be predicted from data about its effects on NOS expression or activity. Combination of substances can produce an effect differing from that of individual substances. This stresses importance of direct measurements of NO in the tissues

Effects of Indole-3-Carbinol and Flavonoids Administered Separately and in Combination on Nitric Oxide Production and iNOS Expression in Rats