Potent inhibition of macrophage migration inhibitory factor (MIF) by myeloperoxidase (MPO)-dependant oxidation of epicatechins

The objective of this study was to determine if MIF was susceptible to modification by epicatechins, a group of dietary flavonoids with known anti-inflammatory properties. Epicatechins are substrates for peroxidases including the neutrophil-derived enzyme myeloperoxidase. Here we show that oxidation of the catechol moiety of epicatechins to a ο-quinone by myeloperoxidase generates potent MIF inhibitors. Near complete inhibition of MIF by the MPO/H2O2/EC system was achieved at equimolar concentrations of EC and MIF even in the presence of other MPO substrates. We characterized the modification introduced by oxidized (-)-epicatechin on MIF by LC/MS and found it to occur at the N-terminal proline. We propose that MIF inhibition by oxidized epicatechins contributes to the anti-inflammatory activity of these compounds.

Source: BJ Energy - June 11, 2014 Category: Biochemistry Authors: N Dickerhof, N J Magon, J D A Tyndall, A J Kettle, M B Hampton Tags: BJ Energy Source Type: research