Effects of flavonols on the generation of superoxide anion radicals by xanthine oxidase and stimulated neutrophils

The effects of three aglycon flavonols (myricetin, quercetin, and kaempferol) and the natural glycoside rutin on superoxide anion radical generating systems were investigated. Quercetin, myricetin, and kaempferol inhibited the formation of uric acid from xanthine by xanthine oxidase, while rutin was ineffective. The generation of superoxide anion radicals by this system was determined by either reduction of cytochrome c or Pholasin luminescence. A scavenging of superoxide was only observed for myricetin and to a small extent for rutin. All flavonols tested inhibited the Pholasin luminescence of fMet-Leu-Phe-stimulated neutrophils. Rutin influenced the oxidative burst of neutrophils in the same way as wortmannin and LY294002, two inhibitors of the phosphoinositide 3-kinase gamma. Indeed, rutin inhibited the activity of this enzyme, whereas the three other flavonols showed no effect. Thus, an inhibition of enzymes involved in signaling rather than a scavenging of superoxide anion radicals dominates in fMet-Leu-Phe-stimulated neutrophils exposed to flavonols. (C) 2001 Academic Press.