Hydroxychavicol, a novel betel leaf component, inhibits platelet aggregation by suppression of cyclooxygenase, thromboxane production and calcium mobilization
Journal
British Journal of Pharmacology
Journal Volume
152
Journal Issue
1
Pages
73-82
Date Issued
2007
Author(s)
Chang M.C.
Uang B.J.
Tsai C.Y.
Wu H.L.
Lee C.S.
Chang C.H.
Kao C.J.
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. ? 2007 Nature Publishing Group All rights reserved.
SDGs
Other Subjects
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
Type
journal article