Antiplatelet effect of phloroglucinol is related to inhibition of cyclooxygenase, reactive oxygen species, ERK/p38 signaling and thromboxane A2 production

Platelet dysfunction is a major risk factor of cardiovascular diseases such as atherosclerosis, stroke and myocardial infarction. Many antiplatelet agents are used for prevention and treatment of these diseases. In this study, phloroglucinol (2.5-25 mu M) suppressed AA-induced platelet aggregation and thromboxane B-2 (TXB2) production, but not U46619-induced platelet aggregation. Phloroglucinol (100-250 mu M) showed little cytotoxicity to platelets. Phloroglucinol inhibited the COX-1 and COX-2 activities by 45-74% and 49-72% respectively at concentrations of 10-50 mu M. At concentrations of 1 and 5 mu M, phloroglucinol attenuated the AA-induced ROS production in platelets by 30% and 53%, with an IC50 of 13.8 mu M. Phloroglucinol also inhibited the PMA-stimulated ROS production in PMN. Preincubation of platelets by phloroglucinol (10-25 mu M) markedly attenuated the AA-induced ERK and p38 phosphorylation. Intravenous administration of phloroglucinol (2.5 and 5 mu mol/mouse) suppressed the ex vivo AA-induced platelet aggregation by 57-71%. Phloroglucinol administration also elevated the mice tail bleeding time. Moreover, phloroglucinol inhibited the IL-1 beta-induced PGE(2) production in pulp fibroblasts. These results indicate that antiplatelet and anti-inflammatory effects of phloroglucinol are related to inhibition of COX, ROS and TXA2 production as well as ERK/p38 phosphorylation in platelets. Phloroglucinol further suppress PMA-induced ROS production in PMN. The antiplatelet effect of phloroglucinol was confirmed by ex vivo study. Clinically, the consumption of phloroglucinol-containing food/natural products as nutritional supplement may be helpful to cardiovascular health. Phloroglucinol has potential pharmacological use. (C) 2012 Elsevier Inc. All rights reserved.