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

The mixture of flavonolignans [Legalon(R) : silybin (2a), isosilybin (3), s ilydianin (4) and silychristin (5)] and derivatives of silybin (2b-d) were assessed for their inhibitory activity on the oxidative burst of PMA-stimul ated human PMNLs. The inhibitory effect of flavonolignans on O-2(-) release were compared with that of vitamin E (1). The flavonolignans tested exhibi ted the following order in inhibition Of O-2(-) release by PMA-stimulated P MNLs: 5,7,4 "- trimethylsilybin (2c) vitamin E (1) > Legalon(R) > peracetyl silybin (2b) > silybin (2a) > peracetyl-5,7,4 " -trimethylsilybin (2d). The flavonolignans inhibited not only the O-2(-) release, but also the H2O2 fo rmation in PMA-stimulated PMNLs. The inhibitory capacity of flavonolignans on H2O2 formation was similar to their inhibitory capacity on O-2(-) releas e. These data suggest that the flavonolignans have antioxidant properties o n the PMNL oxidative burst. The fact that the trimethyl derivative of silyb in (2c) has a greater inhibitory effect than silybin itself suggests that t he efficacy of the antioxidant properties is dependent on the lipophilicity of the molecules. This is underlined by the fact that peracetylation of al l of the hydroxyl groups in silybin resulted in a total loss of the antioxi dant activity of the molecule. In summary, flavonolignans inhibit the oxida tive burst of PMNLs, and this inhibitory effect depends on the chemical str ucture of the flavonolignans. Copyright (C) 2001 John Wiley & Sons, Ltd.