https://scholars.lib.ntu.edu.tw/handle/123456789/569439
標題: | Antiplatelet effect of phloroglucinol is related to inhibition of cyclooxygenase, reactive oxygen species, ERK/p38 signaling and thromboxane A 2 production | 作者: | Chang M.-C. HSIAO-HUA CHANG Chan C.-P. HAN-YI E. CHOU BEI-EN CHANG Yeung S.-Y. TONG-MEI WANG JIIANG-HUEI JENG |
公開日期: | 2012 | 卷: | 263 | 期: | 3 | 起(迄)頁: | 287-295 | 來源出版物: | Toxicology and Applied Pharmacology | 摘要: | 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 (2.5-25μM) suppressed AA-induced platelet aggregation and thromboxane B 2 (TXB 2) production, but not U46619-induced platelet aggregation. Phloroglucinol (100-250μM) showed little cytotoxicity to platelets. Phloroglucinol inhibited the COX-1 and COX-2 activities by 45-74% and 49-72% respectively at concentrations of 10-50μM. At concentrations of 1 and 5μM, phloroglucinol attenuated the AA-induced ROS production in platelets by 30% and 53%, with an IC 50 of 13.8μM. Phloroglucinol also inhibited the PMA-stimulated ROS production in PMN. Preincubation of platelets by phloroglucinol (10-25μM) markedly attenuated the AA-induced ERK and p38 phosphorylation. Intravenous administration of phloroglucinol (2.5 and 5μmol/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-1β-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. ? 2012 Elsevier Inc. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84865410703&doi=10.1016%2fj.taap.2012.06.021&partnerID=40&md5=b0a5ce35f3d41468482def60eeccce14 https://scholars.lib.ntu.edu.tw/handle/123456789/569439 |
ISSN: | 0041-008X | DOI: | 10.1016/j.taap.2012.06.021 | SDG/關鍵字: | 15 hydroxy 11alpha,9alpha epoxymethanoprosta 5,13 dienoic acid; cyclooxygenase 1; cyclooxygenase 2; interleukin 1beta; mitogen activated protein kinase p38; phloroglucinol; prostaglandin E2; prostaglandin synthase; reactive oxygen metabolite; thromboxane A2; thromboxane B2; animal experiment; antiinflammatory activity; article; bleeding time; controlled study; cytotoxicity; drug activity; drug effect; enzyme activity; enzyme inhibition; ex vivo study; fibroblast; male; mouse; nonhuman; protein phosphorylation; signal transduction; thrombocyte aggregation; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Arachidonic Acid; Blood Platelets; Cyclooxygenase 1; Cyclooxygenase 2; Dose-Response Relationship, Drug; Humans; Inhibitory Concentration 50; Interleukin-1beta; Male; Mice; Mice, Inbred ICR; p38 Mitogen-Activated Protein Kinases; Phloroglucinol; Phosphorylation; Platelet Aggregation; Platelet Aggregation Inhibitors; Rabbits; Reactive Oxygen Species; Signal Transduction; Thromboxane A2; Mus |
顯示於: | 臨床牙醫學研究所 |
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