Antiplatelet effect of green tea catechins: a possible mechanism through arachidonic acid pathway.
We have previously reported that green tea catechins (GTC) showed an antithrombotic activity, which might be due to antiplatelet effect rather than anticoagulation. The present study was performed to investigate the effect of GTC on the arachidonic acid (AA) metabolism in order to elucidate a possible antiplatelet mechanism. GTC inhibited the collagen-, AA- and U46619-induced rabbit platelet aggregation in vitro in a concentration-dependent manner, with IC50 values of 61.0+/-2.5, 105.0+/-4.9 and 67.0+/-3.2 microg/ml, respectively. Moreover, GTC administered orally into rats inhibited the AA-induced platelet aggregation ex vivo by 46.9+/-6.1% and 95.4+/-2.2% at the doses of 25 and 50 mg/kg, respectively. [3H]AA liberation induced by collagen in [3H]AA incorporated rabbit platelets was significantly suppressed by GTC compared to the control. GTC also significantly inhibited the thromboxane A2 (TXA2) and prostaglandin D2 (PGD2) generations induced by addition of AA in intact rabbit platelets. GTC significantly inhibited TXA2 synthase activity in a concentration-dependent manner. Moreover, adenosine triphosphate (ATP) release from dense granule was inhibited by GTC in washed platelets. These results suggest that the antiplatelet activity of GTC may be due to the inhibition of TXA2 formation through the inhibition of AA liberation and TXA2 synthase.
Son
Dong-Ju
DJ
College of Natural Sciences, Soonchunhyang University, Asan 336-745, South Korea.
Cho
Mi-Ra
MR
Jin
Yong-Ri
YR
Kim
Soo-Yeon
SY
Park
Young-Hyun
YH
Lee
Soo-Hwan
SH
Akiba
Satoshi
S
Sato
Takashi
T
Yun
Yeo-Pyo
YP
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D028241:Camellia sinensis / Q000737:chemistry*; D002392:Catechin / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D015539:Platelet Activation / Q000187:drug effects*; D015230:Prostaglandin D2 / Q000378:metabolism; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects; D013928:Thromboxane A2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000378:metabolism
D010936:Plant Extracts; D016718:Arachidonic Acid; D013928:Thromboxane A2; D002392:Catechin; D013930:Thromboxane-A Synthase; D015230:Prostaglandin D2