title: Tea polyphenols inhibit acetyl-CoA:1-alkyl-sn-glycero-3-phosphocholine acetyltransferase (a key enzyme in platelet-activating factor biosynthesis) and platelet-activating factor-induced platelet aggregation.
abstract: BACKGROUND
  Tea extracts have antiallergic and anti-inflammatory actions in rats and mice. However the mechanism through which tea polyphenols act in vivo are still incompletely understood. We found inhibitory effects of black tea extracts on an fMLP-induced aggregating response in a rabbit platelet-polymorphonuclear leukocyte (PMN) system.
  
  
  METHODS
  To elucidate whether 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) production in PMNs and/or PAF-stimulated platelet activation were inhibited, the effects of tea polyphenols were investigated on the enzyme activity of acetyl-CoA:1-alkyl-sn-glycero-3-phosphocholine acetyltransferase (EC 2.3.1.67), PAF biosynthesis in A23187-activated rabbit PMNs, and rabbit platelet aggregation. By comparing the inhibitory effects of 31 galloyl esters and gallic acid, the structure-inhibitory activity relationship was characterized.
  
  
  RESULTS
  Theaflavin and its galloyl esters and pentagalloyl glucose were found to be potent inhibitors of the acetyltransferase (IC(50) = 28-58 microM) and the PAF biosynthesis as well as (-)-epicatechin-3-O-gallate (IC(50) = 72 +/- 13 microM) and (-)-epigallocatechin-3-O-gallate (IC(50) = 46 +/- 6 microM). On the other hand, flavan-3-ols without galloyl group at C-3 and gallic acid did not show significant enzyme inhibition. In addition, theaflavin and its galloyl esters (IC(50) = 32-77 microM) and geranyl gallate, farnesyl gallate and geranylgeranyl gallate (IC(50) = 6.4-7.6 microM) were found to be potent inhibitors of PAF- and TPA-induced rabbit platelet aggregation but not A23187-induced aggregation.
  
  
  CONCLUSIONS
  Theaflavin and its galloyl esters in black tea extract, and isoprenyl gallates were potent inhibitors of PAF synthesis and platelet aggregation and these activities may be relevant to the claimed therapeutic effects of tea extracts.
authors.affiliation: Department of Pharmaco-Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Sugatani
authors.forename: Nana
authors.initials: N
authors.lastname: Fukazawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Ujihara
authors.forename: Kouichi
authors.initials: K
authors.lastname: Yoshinari
authors.forename: Ikuo
authors.initials: I
authors.lastname: Abe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Noguchi
authors.forename: Masao
authors.initials: M
authors.lastname: Miwa
mesh_terms: D000123:Acetyltransferases / Q000096:biosynthesis* / Q000187:drug effects*; D000818:Animals; D044946:Biflavonoids / Q000494:pharmacology; D002392:Catechin / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D023421:Models, Animal; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology; D010636:Phenols / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000187:drug effects*; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D059808:Polyphenols; D011817:Rabbits; D012250:Rheum / Q000737:chemistry; D013662:Tea / Q000737:chemistry*; D013997:Time Factors
chemical_list: D044946:Biflavonoids; D002614:Chelating Agents; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D010972:Platelet Activating Factor; D059808:Polyphenols; D013662:Tea; C056068:theaflavin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002392:Catechin; D000123:Acetyltransferases; C027628:acetyl-CoA-1-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase