Effect of three flavonoids, 5,7,3 ',4 '-tetrahydroxy-3-methoxy flavone, luteolin, and quercetin, on the stimulus-induced superoxide generation and tyrosyl phosphorylation of proteins in human neutrophil

The effect of three flavonoids, 5,7,3 ' ,4 ' -tetrahydoxy-3-methoxy flavone (THMF), luteolin, and quercetin, on the stimulus-induced superoxide genera tion and tyrosyl phosphorylation of proteins in human neutrophils were inve stigated. When the cells were preincubated with these flavonoids, the super oxide generation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) was significantly suppressed, showing a dependence on amounts of the flavon oid. The suppressing effect of the flavonoid was THMF > luteolin > querceti n. These flavonoids also suppressed the superoxide generation induced by ph orbol 12-myristate 13-acetate. In this case also, THMF was more effective t han luteolin and quercetin. On the other hand, the superoxide generation in duced by arachidonic acid was markedly suppressed by quercetin. The suppres sing effect was quercetin THMF > luteolin. THMF, luteolin, and quercetin si gnificantly suppressed tyrosyl phosphorylation of 80.1-, 58.0-, and 45.0-kD a proteins in fMLP-treated human neutrophils. The suppression depended on t he concentration of the flavonoids, and the inhibition of tyrosyl phosphory lation was in parallel to that of the fMLP-induced superoxide generation, r espectively. While luteolin and quercetin showed a weak hemolytic activity at 2.5 mM, THAW showed almost no hemolytic activity even at 5 mM, suggestin g an advantage of THMF for its clinical use. (C) 2001 Academic Press.