(-)Epigallocatechin-3-gallate inhibits leukocyte elastase: potential of the phyto-factor in hindering inflammation, emphysema, and invasion.
Flavanol (-)epigallocatechin-3-gallate is shown to be a potent natural inhibitor of leukocyte elastase that may be used to reduce elastase-mediated progression to emphysema and tumor invasion. This phyto-factor, abundant in green tea, exerts a dose-dependent, noncompetitive inhibition of leukocyte elastase at a noncytotoxic concentration and is effective in neutrophil culture. This inhibition shows an IC(50) of 0.4 microM, 30 times higher than the alpha1-protease inhibitor but lower than other known natural and synthetic elastase inhibitors. The flavanol inhibits leukocyte elastase at concentrations of 50, 150, and 2500 times lower than that effective on gelatinases (MMP-2 and MMP-9), thrombin, and cathepsin G, respectively, and also blocks elastase-mediated activation of MMP-9.
Sartor
Luigi
L
Department of Experimental Biomedical Sciences, Medical School of Padova, Italy.
Pezzato
Elga
E
Garbisa
Spiridione
S
D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000627:therapeutic use; D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004646:Emphysema / Q000188:drug therapy; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D018093:Gelatinases / Q000037:antagonists & inhibitors; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D009504:Neutrophils / Q000201:enzymology*; D008517:Phytotherapy; D012697:Serine Endopeptidases; D013917:Thrombin / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D002392:Catechin; C045651:epigallocatechin gallate; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D019272:Leukocyte Elastase; D013917:Thrombin; D018093:Gelatinases