title: Inhibition of Myeloperoxidase- and Neutrophil-Mediated Hypochlorous Acid Formation in Vitro and Endothelial Cell Injury by (-)-Epigallocatechin Gallate.
abstract: Myeloperoxidase (MPO) plays important roles in various diseases through its unique chlorinating activity to catalyze excess hypochlorous acid (HOCl) formation. Epidemiological studies indicate an inverse correlation between plant polyphenol consumption and the incidence of cardiovascular diseases. Here we showed that (-)-epigallocatechin gallate (EGCG), the main flavonoid present in green tea, dose-dependently inhibited MPO-mediated HOCl formation in vitro (chlorinating activities of MPO: 50.2 ± 5.7% for 20 μM EGCG versus 100 ± 5.6% for control, P < 0.01). UV-vis spectral and docking studies indicated that EGCG bound to the active site (heme) of MPO and resulted in the accumulation of compound II, which was unable to produce HOCl. This flavonoid also effectively inhibited HOCl generation in activated neutrophils (HOCl formation: 65.0 ± 5.6% for 20 μM EGCG versus 100 ± 6.2% for control, P < 0.01) without influencing MPO and Nox2 release and superoxide formation, suggesting that EGCG specifically inhibited MPO but not NADPH oxidase activity in activated neutrophils. Moreover, EGCG inhibited MPO (or neutrophil)-mediated HOCl formation in human umbilical vein endothelial cells (HUVEC) culture and accordingly protected HUVEC from MPO (or neutrophil)-induced injury (P < 0.05, all cases), although it did not induce cytotoxicity to HUVEC (P > 0.05, all cases). Our results indicate that dietary EGCG is an effective and specific inhibitor of MPO activity and may participate in the regulation of immune responses at inflammatory sites.
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education, Key Laboratory of Green Chemistry in Jiangxi Province, and College of Chemistry and Chemical Engineering, Jiangxi Normal University , Nanchang, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Tian
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education, Key Laboratory of Green Chemistry in Jiangxi Province, and College of Chemistry and Chemical Engineering, Jiangxi Normal University , Nanchang, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education, Key Laboratory of Green Chemistry in Jiangxi Province, and College of Chemistry and Chemical Engineering, Jiangxi Normal University , Nanchang, China.
authors.forename: Yi-Yuan
authors.initials: YY
authors.lastname: Peng
authors.affiliation: Key Laboratory of Functional Small Organic Molecule, Ministry of Education, Key Laboratory of Green Chemistry in Jiangxi Province, and College of Chemistry and Chemical Engineering, Jiangxi Normal University , Nanchang, China.
authors.forename: Naihao
authors.identifier: http://orcid.org/0000-0003-3336-2502
authors.initials: N
authors.lastname: Lu
mesh_terms: D001665:Binding Sites; D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015536:Down-Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism*; D062105:Molecular Docking Simulation; D009504:Neutrophils / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D009195:Peroxidase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D006997:Hypochlorous Acid; D002392:Catechin; C045651:epigallocatechin gallate; D009195:Peroxidase
keywords: EGCG; endothelial cells; hypochlorous acid; myeloperoxidase; neutrophils