https://scholars.lib.ntu.edu.tw/handle/123456789/545895
標題: | Hydroxychavicol, a novel betel leaf component, inhibits platelet aggregation by suppression of cyclooxygenase, thromboxane production and calcium mobilization | 作者: | Chang M.C. Uang B.J. Tsai C.Y. Wu H.L. BOR-RU LIN Lee C.S. YI-JANE CHEN Chang C.H. YI-LING TSAI Kao C.J. JIIANG-HUEI JENG |
公開日期: | 2007 | 卷: | 152 | 期: | 1 | 起(迄)頁: | 73-82 | 來源出版物: | British Journal of Pharmacology | 摘要: | Background and purpose: Platelet hyperactivity is important in the pathogenesis of cardiovascular diseases. Betel leaf (PBL) is consumed by 200-600 million betel quid chewers in the world. Hydroxychavicol (HC), a betel leaf component, was tested for its antiplatelet effect. Experimental approach: We tested the effect of HC on platelet aggregation, thromboxane B 2 (TXB 2) and reactive oxygen species (ROS) production, cyclooxygenase (COX) activity, ex vivo platelet aggregation and mouse bleeding time and platelet plug formation in vivo. The pharmacokinetics of HC in rats was also assessed. Key results: HC inhibited arachidonic acid (AA) and collagen-induced platelet aggregation and TXB 2 production. HC inhibited the thrombin-induced TXB 2 production, but not platelet aggregation. SQ29548, suppressed collagen- and thrombin-induced TXB 2 production, but not thrombin-induced platelet aggregation. HC also suppressed COX-1/COX-2 enzyme activity and the AA-induced ROS production and Ca 2+ mobilization. HC further inhibited the ex vivo platelet aggregation of platelet-rich plasma (>100 nmole/mouse) and prolonged platelet plug formation (>300 nmole/mouse) in mesenteric microvessels, but showed little effect on bleeding time in mouse tail. Moreover, pharmacokinetics analysis found that more than 99% of HC was metabolized within 3 min of administration in Sprague-Dawley rats in vivo. Conclusions and implications: HC is a potent COX-1/COX-2 inhibitor, ROS scavenger and inhibits platelet calcium signaling, TXB 2 production and aggregation. HC could be a potential therapeutic agent for prevention and treatment of atherosclerosis and other cardiovascular diseases through its anti-inflammatory and antiplatelet effects, without effects on haemostatic functions. ? 2007 Nature Publishing Group All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-34548336803&doi=10.1038%2fsj.bjp.0707367&partnerID=40&md5=b51d7719e1b4bd0c7d4c7a81c43f5f63 https://scholars.lib.ntu.edu.tw/handle/123456789/545895 |
ISSN: | 0007-1188 | DOI: | 10.1038/sj.bjp.0707367 | SDG/關鍵字: | 7 [3 [(4 phenylsemicarbazido)methyl] 7 oxabicyclo[2.2.1]hept 2 yl] 5 heptenoic acid; acetylsalicylic acid; arachidonic acid; betel extract; calcium; celecoxib; cyclooxygenase 1; cyclooxygenase 2; eugenol; hydroxychavicol; lactate dehydrogenase; prostaglandin synthase; reactive oxygen metabolite; thromboxane B2; unclassified drug; animal experiment; antioxidant activity; article; betel nut; bleeding time; calcium mobilization; controlled study; drug blood level; enzyme activity; enzyme inhibition; enzyme linked immunosorbent assay; enzyme repression; fluorescence; fluorometry; high performance liquid chromatography; male; mouse; nonhuman; priority journal; rat; thrombocyte aggregation; thrombosis; Animals; Arachidonic Acid; Bleeding Time; Blood Platelets; Calcium Signaling; Collagen; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Eugenol; Male; Mice; Mice, Inbred ICR; Piper betle; Plant Leaves; Platelet Aggregation; Platelet Aggregation Inhibitors; Rabbits; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Thrombin; Thromboxane B2 |
顯示於: | 醫學系 |
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