title: Epigallocatechin-3-Gallate Inhibition of Myeloperoxidase and Its Counter-Regulation by Dietary Iron and Lipocalin 2 in Murine Model of Gut Inflammation.
abstract: Green tea-derived polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been extensively studied for its antioxidant and anti-inflammatory properties in models of inflammatory bowel disease, yet the underlying molecular mechanism is not completely understood. Herein, we demonstrate that EGCG can potently inhibit the proinflammatory enzyme myeloperoxidase in vitro in a dose-dependent manner over a range of physiologic temperatures and pH values. The ability of EGCG to mediate its inhibitory activity is counter-regulated by the presence of iron and lipocalin 2. Spectral analysis indicated that EGCG prevents the peroxidase-catalyzed reaction by reverting the reactive peroxidase heme (compound I:oxoiron) back to its native inactive ferric state, possibly via the exchange of electrons. Further, administration of EGCG to dextran sodium sulfate-induced colitic mice significantly reduced the colonic myeloperoxidase activity and alleviated proinflammatory mediators associated with gut inflammation. However, the efficacy of EGCG against gut inflammation is diminished when orally coadministered with iron. These findings indicate that the ability of EGCG to inhibit myeloperoxidase activity is one of the mechanisms by which it exerts mucoprotective effects and that counter-regulatory factors such as dietary iron and luminal lipocalin 2 should be taken into consideration for optimizing clinical management strategies for inflammatory bowel disease with the use of EGCG treatment.
authors.affiliation: Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania.
authors.forename: Beng San
authors.initials: BS
authors.lastname: Yeoh
authors.affiliation: Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Aguilera Olvera
authors.affiliation: Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania.
authors.forename: Vishal
authors.initials: V
authors.lastname: Singh
authors.affiliation: Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania.
authors.forename: Xia
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Veterinary and Biomedical Sciences, The Pennsylvania State University, University Park, Pennsylvania.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Kennett
authors.affiliation: Department of Physiology and Pharmacology, Center for Hypertension and Personalized Medicine, The University of Toledo College of Medicine and Life Sciences, Toledo, Ohio.
authors.forename: Bina
authors.initials: B
authors.lastname: Joe
authors.affiliation: Department of Food Science, The Pennsylvania State University, University Park, Pennsylvania.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Lambert
authors.affiliation: Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania; Department of Medicine, The Pennsylvania State University Medical Center, Hershey, Pennsylvania. Electronic address: mvk13@psu.edu.
authors.forename: Matam
authors.initials: M
authors.lastname: Vijay-Kumar
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000378:metabolism; D016264:Dextran Sulfate / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D019266:Iron, Dietary / Q000378:metabolism*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D015513:Oncogene Proteins / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D013662:Tea
chemical_list: D000209:Acute-Phase Proteins; D000975:Antioxidants; D019266:Iron, Dietary; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D013662:Tea; C071332:Lcn2 protein, mouse; D002392:Catechin; D016264:Dextran Sulfate; C045651:epigallocatechin gallate; D009195:Peroxidase