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

M. C. Chang, B. J. Uang, C. Y. Tsai, Hsyueh-Liang Wu, B. R. Lin, C. S. Lee, Y. J. Chen, C. H. Chang, Y. L. Tsai, C. J. Kao, J. H. Jeng

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Pages (from-to)73-82
Number of pages10
JournalBritish Journal of Pharmacology
Volume152
Issue number1
DOIs
Publication statusPublished - 2007 Sep 1

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Thromboxanes
Prostaglandin-Endoperoxide Synthases
Platelet Aggregation
Calcium
Blood Platelets
Thrombin
Reactive Oxygen Species
Cyclooxygenase 1
Bleeding Time
Arachidonic Acid
Cardiovascular Diseases
Collagen
Pharmacokinetics
2-hydroxychavicol
Platelet-Rich Plasma
Calcium Signaling
Cyclooxygenase 2 Inhibitors
Hemostatics
Cyclooxygenase 2
Microvessels

Keywords

  • Betel leaf
  • Calcium
  • Cyclooxygenase
  • Hydroxychavicol
  • Platelet aggregation
  • Thromboxane

ASJC Scopus subject areas

  • Pharmacology

Cite this

Hydroxychavicol, a novel betel leaf component, inhibits platelet aggregation by suppression of cyclooxygenase, thromboxane production and calcium mobilization. / Chang, M. C.; Uang, B. J.; Tsai, C. Y.; Wu, Hsyueh-Liang; Lin, B. R.; Lee, C. S.; Chen, Y. J.; Chang, C. H.; Tsai, Y. L.; Kao, C. J.; Jeng, J. H.

In: British Journal of Pharmacology, Vol. 152, No. 1, 01.09.2007, p. 73-82.

Research output: Contribution to journalArticle

Chang, M. C. ; Uang, B. J. ; Tsai, C. Y. ; Wu, Hsyueh-Liang ; Lin, B. R. ; Lee, C. S. ; Chen, Y. J. ; Chang, C. H. ; Tsai, Y. L. ; Kao, C. J. ; Jeng, J. H. / Hydroxychavicol, a novel betel leaf component, inhibits platelet aggregation by suppression of cyclooxygenase, thromboxane production and calcium mobilization. In: British Journal of Pharmacology. 2007 ; Vol. 152, No. 1. pp. 73-82.
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abstract = "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.",
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AU - Uang, B. J.

AU - Tsai, C. Y.

AU - Wu, Hsyueh-Liang

AU - Lin, B. R.

AU - Lee, C. S.

AU - Chen, Y. J.

AU - Chang, C. H.

AU - Tsai, Y. L.

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AU - Jeng, J. H.

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AB - 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.

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