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


METHODS
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.


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
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.
Chang
M C
MC
Biomedical Science Team, Chang-Gung Institute of Technology, Taoyuan, Taiwan.
Uang
B J
BJ
Tsai
C Y
CY
Wu
H L
HL
Lin
B R
BR
Lee
C S
CS
Chen
Y J
YJ
Chang
C H
CH
Tsai
Y L
YL
Kao
C J
CJ
Jeng
J H
JH
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D003094:Collagen / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005054:Eugenol / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D031721:Piper betle / Q000737:chemistry; D018515:Plant Leaves; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism*
D016861:Cyclooxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D017382:Reactive Oxygen Species; C051268:2-hydroxychavicol; D016718:Arachidonic Acid; D005054:Eugenol; D013929:Thromboxane B2; D003094:Collagen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D013917:Thrombin