Premium
Hydroxychavicol, a novel betel leaf component, inhibits platelet aggregation by suppression of cyclooxygenase, thromboxane production and calcium mobilization
Author(s) -
Chang M C,
Uang B J,
Tsai C Y,
Wu H L,
Lin B R,
Lee C S,
Chen Y J,
Chang C H,
Tsai Y L,
Kao C J,
Jeng J H
Publication year - 2007
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0707367
Subject(s) - calcium , cyclooxygenase , mobilization , platelet , thromboxane a2 , chemistry , thromboxane b2 , thromboxane , platelet aggregation , pharmacology , medicine , biochemistry , enzyme , archaeology , history
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. British Journal of Pharmacology (2007) 152 , 73–82; doi: 10.1038/sj.bjp.0707367