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.

Effects of standardized stem bark extract of Mangifera indica L. in wistar rats with 2,4-dinitrophenylhydrazine-induced haemolytic anaemia

“…23 The branched ether 2,2-dimethoxybutane have been reported to be toxic to microbial membrane. 24 1,2-benzenediol is present in plant-derived products, such as vegetables, fruits, coffee, tea, wine, areca nut and cigarette smoke 25 among them include Diospyros kaki, 26 Annona senegalensis, 27 Petalostigma triloculare 23 among others. Report have shown that 1,2-benzenediol possess antimicrobials as well as antiplatelet 25,26 activity.…”

“…24 1,2-benzenediol is present in plant-derived products, such as vegetables, fruits, coffee, tea, wine, areca nut and cigarette smoke 25 among them include Diospyros kaki, 26 Annona senegalensis, 27 Petalostigma triloculare 23 among others. Report have shown that 1,2-benzenediol possess antimicrobials as well as antiplatelet 25,26 activity. Phenol, 2,4-bis (1, 1-dimethylethyl)-has also been reported in Scolopendra subspinispes with strong antioxidant activity, 28 Pereskia bleo with anticancer activity, 29 and strain of Pseudomonas monteilii PsF84 with antifungal activity, 30 Additionally, vitamin E identified two times at different retention times in this study is a well known antioxidant compound used for the treatment of various illnesses while N-Acetyl-Alpha-D-glucosamine has been used as safe alternative therapies for osteoarthritis,…”

“…The anaemic groups III, IV and V received test extract (25,50, and 100 mg/kg b.wt, p.o.) and VI received standard heamatinic drug Astifer® (50 mg/kg b.wt, p.o.).…”

Effects of TGF‐β1 on plasminogen activation in human dental pulp cells: Role of ALK5/Smad2, TAK1 and MEK/ERK signalling

“…In total, 1.5 × 10 6 pulp cells were seeded onto 10‐cm culture dishes in 10 ml DMEM comprising 10% FBS. After cell attachment overnight, cells were exposed to fresh medium containing various concentrations of TGF‐β1 (0.5, 1, 5, 10 ng/ml) for 24 h. Then, culture medium was decanted and cells were washed with phosphate‐buffered saline and dissolved in lysis buffer containing 10 m m Tris–HCl, pH 7; 140 m m sodium chloride; 3 m m magnesium chloride; 0.5% NP‐40; 2 m m phenylmethylsulphonyl fluoride; 1% aprotinin; and 5 m m dithiothreitol (Chang et al , ,b, ). The same amount of proteins (30–50 μg/lane) in cell lysates was loaded for 12.5% sodium dodecyl sulphate–polyacrylamide gel electrophoresis, and transferred to a polyvinylidene fluoride membrane.…”

Investigation of a Thromboxane A 2 Receptor–Based Vaccine for Managing Thrombogenesis

“…Consequently, platelets will interact with the exposed subendothelial matrix,4, 5 leading to intraplatelet signaling and activation, which is associated with several events, including release of arachidonic acid from the membrane phospholipids 6, 7. The liberated arachidonic acid is metabolized by the cyclooxygenase enzyme and thromboxane A 2 (TXA 2 ) synthase, leading to the formation of TXA 2 8, 9, 10. TXA 2 , a well‐studied platelet agonist, is a labile lipid mediator that acts through binding to its G‐protein–coupled receptor11, 12, 13 (namely, the TXA 2 receptor [TPR]).…”