Antiplatelet actions of some coumarin compounds isolated from plant sources.
Xanthyletin, xanthoxyletin, suberosin (all from Citrus grandis), aurapten (from Severinia huxifolia) and poncitrin (from Poncirus trifoliata) were isolated and their chemical structures were characterized to be coumarin compounds. All these coumarin compounds except xanthyletin inhibited the aggregation and ATP release of rabbit platelets induced by arachidonic acid, collagen, ADP, platelet-activating factor (PAF) or U46619 (a thromboxane A2 analog). Thrombin-induced ATP release, but not the aggregation, was also inhibited by these compounds. Xanthyletin inhibited only platelet aggregation induced by arachidonic acid and collagen, while poncitrin inhibited that caused by PAF more markedly than other coumarin compounds. The thromboxane B2 formation in washed platelets caused by arachidonic acid and collagen was suppressed by these coumarin compounds. The phosphoinositide breakdown caused by collagen and PAF was also inhibited by these compounds. They did not affect fibrinogen-induced aggregation of elastase-treated platelets. These antiplatelet actions were immediate, reversible by washout and independent on the incubation time (except suberosin). Antiaggregating effect was also studied by an electrical impedance method and the inhibitory effect of coumarin compounds on the whole blood and platelet-rich plasma was much less than that of platelet suspension in the aggregation induced by collagen, PAF and ADP. It is concluded that the antiplatelet actions of these coumarin compounds are due to the inhibition on thromboxane A2 formation and phosphoinositides breakdown.
Teng
C M
CM
Pharmacological Institute, College of Medicine, National Taiwan University, Taipei.
Li
H L
HL
Wu
T S
TS
Huang
S C
SC
Huang
T F
TF
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003374:Coumarins / Q000302:isolation & purification*; D008563:Membrane Lipids / Q000378:metabolism; D015394:Molecular Structure; D010743:Phospholipids / Q000378:metabolism; D010944:Plants / Q000737:chemistry*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000302:isolation & purification*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors; D011817:Rabbits; D013917:Thrombin / Q000037:antagonists & inhibitors; D013929:Thromboxane B2 / Q000096:biosynthesis
D003374:Coumarins; D008563:Membrane Lipids; D010743:Phospholipids; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011450:Prostaglandin Endoperoxides, Synthetic; C518975:suberosin; D016718:Arachidonic Acid; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D013917:Thrombin