title: Plant-derived anti-inflammatory compounds affect MIF tautomerase activity.
abstract: The cytokine macrophage migration inhibitory factor (MIF) has recently emerged as a crucial factor in the pathogenesis of rheumatoid arthritis (RA). It is debated whether the MIF mediated tautomeric conversion of either phenylpyruvate or of its other phenolic substrates is implicated in the pro-inflammatory action of this cytokine. Traditional herbal remedies have been used for centuries to alleviate inflammatory ailments of many kinds including arthritis. Several of their active ingredients identified are mono- or poly-phenol derivatives. In the present study the effect of some anti-inflammatory plant phenols on MIF mediated tautomerism of phenylpyruvate was investigated. Curcumin and caffeic acid were found to be the most potent inhibitors, exhibiting IC(50) values in the submicromolar range in the ketonase assay. Resveratrol and umbelliferon were almost as potent inhibitors as the antipyretic-analgetic drug acetaminophen. Our results reveal MIF as a possible target for the herbal anti-rheumatic agents.
authors.affiliation: Department of Pathophysiology, Faculty of Medicine, University of Pécs, 12, Szigeti Str. H-7624 Pécs, Hungary. valeria.molnar@aok.pte.hu
authors.forename: Valeria
authors.initials: V
authors.lastname: Molnar
authors.forename: János
authors.initials: J
authors.lastname: Garai
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification* / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology; D002417:Cattle; D003474:Curcumin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007668:Kidney / Q000201:enzymology; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology; D010667:Phenylpyruvic Acids / Q000378:metabolism; D010693:Phloretin / Q000494:pharmacology; D008517:Phytotherapy; D010946:Plants, Medicinal / Q000737:chemistry*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002109:Caffeic Acids; D004791:Enzyme Inhibitors; D008263:Macrophage Migration-Inhibitory Factors; D010636:Phenols; D010667:Phenylpyruvic Acids; D013267:Stilbenes; D019746:Intramolecular Oxidoreductases; C022346:phenylpyruvate tautomerase; D003474:Curcumin; D000077185:Resveratrol; D010693:Phloretin; C040048:caffeic acid; C031606:phenylpyruvic acid