Ellagic Acid, a Dietary Polyphenol, Inhibits Tautomerase Activity of Human Macrophage Migration Inhibitory Factor and Its Pro-inflammatory Responses in Human Peripheral Blood Mononuclear Cells

Abstract

Ellagic acid (EA), a phenolic lactone, inhibited tautomerase activity of human macrophage migration inhibitory factor (MIF) non-competitively (Ki = 1.97 ± 0.7 µM). The binding of EA to MIF was determined by following the quenching of tryptophan fluorescence. We synthesized several EA-derivatives and their structure-activity-relation studies indicated that the planar conjugated lactone moiety of EA was essential for MIF inhibition. MIF induces nuclear translocation of NF-κB and chemotaxis of peripheral blood mononuclear cells (PBMCs) to promote inflammation. We were interested in evaluating the effect of EA on nuclear translocation of NF-κB and chemotactic activity in human PBMCs in presence of MIF. Results showed that EA inhibited MIF-induced NF-κB nuclear translocation in PBMCs as evident from confocal immuno-fluorescence microscopic data. EA also inhibited MIF-mediated chemotaxis of PBMCs. Thus, we report MIF-inhibitory activity of EA and inhibition of MIF-mediated pro-inflammatory responses in PBMCs by EA.