title: Antiplatelet effect of catechol is related to inhibition of cyclooxygenase, reactive oxygen species, ERK/p38 signaling and thromboxane A2 production.
abstract: Catechol (benzenediol) is present in plant-derived products, such as vegetables, fruits, coffee, tea, wine, areca nut and cigarette smoke. Because platelet dysfunction is a risk factor of cardiovascular diseases, including stroke, atherosclerosis and myocardial infarction, the purpose of this study was to evaluate the anti-platelet and anti-inflammatory effect of catechol and its mechanisms. The effects of catechol on cyclooxygenase (COX) activity, arachidonic acid (AA)-induced aggregation, thromboxane B2 (TXB2) production, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) production and extracellular signal-regulated kinase (ERK)/p38 phosphorylation were determined in rabbit platelets. In addition, its effect on IL-1β-induced prostaglandin E2 (PGE2) production by fibroblasts was determined. The ex vivo effect of catechol on platelet aggregation was also measured. Catechol (5-25 µM) suppressed AA-induced platelet aggregation and inhibited TXB2 production at concentrations of 0.5-5 µM; however, it showed little cytotoxicity and did not alter U46619-induced platelet aggregation. Catechol (10-50 µM) suppressed COX-1 activity by 29-44% and COX-2 activity by 29-50%. It also inhibited IL-1β-induced PGE2 production, but not COX-2 expression of fibroblasts. Moreover, catechol (1-10 µM) attenuated AA-induced ROS production in platelets and phorbol myristate acetate (PMA)-induced ROS production in human polymorphonuclear leukocytes. Exposure of platelets to catechol decreased AA-induced ERK and p38 phosphorylation. Finally, intravenous administration of catechol (2.5-5 µmole/mouse) attenuated ex vivo AA-induced platelet aggregation. These results suggest that catechol exhibited anti-platelet and anti-inflammatory effects, which were mediated by inhibition of COX, ROS and TXA2 production as well as ERK/p38 phosphorylation. The anti-platelet effect of catechol was confirmed by ex vivo analysis. Exposure to catechol may affect platelet function and thus cardiovascular health.
authors.affiliation: Biomedical Science Team, Chang Gung University of Science and Technology, Taoyuan,Taiwan.
authors.forename: Mei-Chi
authors.initials: MC
authors.lastname: Chang
authors.affiliation: Laboratory of Pharmacology & Toxicology, Graduate Institute of Clinical Dentistry and Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan.
authors.forename: Hsiao-Hua
authors.initials: HH
authors.lastname: Chang
authors.affiliation: Laboratory of Pharmacology & Toxicology, Graduate Institute of Clinical Dentistry and Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan.
authors.forename: Tong-Mei
authors.initials: TM
authors.lastname: Wang
authors.affiliation: Department of Dentistry, Chang Gung Memorial Hospital and Chang Gung University, Taipei, Taiwan.
authors.forename: Chiu-Po
authors.initials: CP
authors.lastname: Chan
authors.affiliation: Department of Diagnotherapeutics, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Bor-Ru
authors.initials: BR
authors.lastname: Lin
authors.affiliation: Department of Dentistry, Chang Gung Memorial Hospital and Chang Gung University, Taipei, Taiwan.
authors.forename: Sin-Yuet
authors.initials: SY
authors.lastname: Yeung
authors.affiliation: Laboratory of Pharmacology & Toxicology, Graduate Institute of Clinical Dentistry and Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan.
authors.forename: Chien-Yang
authors.initials: CY
authors.lastname: Yeh
authors.affiliation: Biomedical Science Team, Chang Gung University of Science and Technology, Taoyuan,Taiwan.
authors.forename: Ru-Hsiu
authors.initials: RH
authors.lastname: Cheng
authors.affiliation: Laboratory of Pharmacology & Toxicology, Graduate Institute of Clinical Dentistry and Department of Dentistry, National Taiwan University Hospital and National Taiwan University Medical College, Taipei, Taiwan.
authors.forename: Jiiang-Huei
authors.initials: JH
authors.lastname: Jeng
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002396:Catechols / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D010979:Platelet Function Tests / Q000379:methods; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D002396:Catechols; D016861:Cyclooxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D017382:Reactive Oxygen Species; D016718:Arachidonic Acid; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D048051:p38 Mitogen-Activated Protein Kinases; C034221:catechol