Inhibition of the superoxide anion release and hydrogen peroxide formation in PMNLs by flavonolignans

The mixture of flavonolignans [Legalon: silybin (2a), isosilybin (3), silydianin (4) and silychristin (5)] and derivatives of silybin (2b-d) were assessed for their inhibitory activity on the oxidative burst of PMA-stimulated human PMNLs. The inhibitory effect of flavonolignans on O(2)(-) release were compared with that of vitamin E (1). The flavonolignans tested exhibited the following order in inhibition of O(2)(-) release by PMA-stimulated PMNLs: 5,7,4"- trimethylsilybin (2c) approximately vitamin E (1) > Legalon >or= peracetylsilybin (2b) > silybin (2a) > peracetyl-5,7,4"-trimethylsilybin (2d). The flavonolignans inhibited not only the O(2)(-) release, but also the H(2)O(2) formation in PMA-stimulated PMNLs. The inhibitory capacity of flavonolignans on H(2)O(2) formation was similar to their inhibitory capacity on O(2)(-) release. These data suggest that the flavonolignans have antioxidant properties on the PMNL oxidative burst. The fact that the trimethyl derivative of silybin (2c) has a greater inhibitory effect than silybin itself suggests that the efficacy of the antioxidant properties is dependent on the lipophilicity of the molecules. This is underlined by the fact that peracetylation of all of the hydroxyl groups in silybin resulted in a total loss of the antioxidant activity of the molecule. In summary, flavonolignans inhibit the oxidative burst of PMNLs, and this inhibitory effect depends on the chemical structure of the flavonolignans.