Hydroxychavicol, a novel betel leaf component, inhibits platelet aggregation by suppression of cyclooxygenase, thromboxane production and calcium mobilization

• Published in: British journal of pharmacology Vol. 152; no. 1; pp. 73 - 82
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.09.2007; Nature Publishing; Nature Publishing Group
• Subjects: Animals; Arachidonic Acid - metabolism; betel leaf; Biological and medical sciences; Bleeding Time; Blood Platelets - drug effects; Blood Platelets - enzymology; Blood Platelets - metabolism; calcium; Calcium Signaling - drug effects; Collagen - metabolism; cyclooxygenase; Cyclooxygenase 1 - metabolism; Cyclooxygenase 2 - metabolism; Cyclooxygenase Inhibitors - isolation & purification; Cyclooxygenase Inhibitors - pharmacokinetics; Cyclooxygenase Inhibitors - pharmacology; Dose-Response Relationship, Drug; Eugenol - analogs & derivatives; Eugenol - isolation & purification; Eugenol - pharmacokinetics; Eugenol - pharmacology; hydroxychavicol; Male; Medical sciences; Mice; Mice, Inbred ICR; Pharmacology. Drug treatments; Piper betle - chemistry; Plant Leaves; platelet aggregation; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - isolation & purification; Platelet Aggregation Inhibitors - pharmacokinetics; Platelet Aggregation Inhibitors - pharmacology; Rabbits; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Research Papers; Thrombin - metabolism; thromboxane; Thromboxane B2 - metabolism; Prostaglandin-endoperoxide synthase; hydroxychavicol; Calcium; Enzyme; Arachidonic acid derivatives; cyclooxygenase; Plant leaf; Inorganic element; platelet aggregation; Aggregation; Platelet; Eicosanoid; Oxidoreductases; Thromboxane; betel leaf
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0707367

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 B2 (TXB2) 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 TXB2 production. HC inhibited the thrombin‐induced TXB2 production, but not platelet aggregation. SQ29548, suppressed collagen‐ and thrombin‐induced TXB2 production, but not thrombin‐induced platelet aggregation. HC also suppressed COX‐1/COX‐2 enzyme activity and the AA‐induced ROS production and Ca2+ 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, TXB2 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