Mechanisms involved in the antiplatelet effect of C-phycocyanin.
C-phycocyanin (cpc), a biliprotein isolated from Spirulina platensis, has been reported to exert many therapeutic and nutritional values. In the present study, we examined whether cpc has an antiplatelet activity in vitro and further investigated the possible anti-aggregatory mechanisms involved. Our results showed that preincubation of cpc (1-50 microg/ml) with rabbit washed platelets dose-dependently inhibited the platelet aggregation induced by collagen (10 microg/ml) or arachidonic acid (100 microm), with an IC50 of about 10 microg/ml. Furthermore, the thromboxane B2 formation caused by collagen or arachidonic acid was significantly inhibited by cpc due to suppression of cyclooxygenase and thromboxane synthase activity. Similarly, the rise of platelet intracellular calcium level stimulated by arachidonic acid and collagen-induced platelet membrane surface glycoprotein IIb/IIIa expression were also attenuated by cpc. In addition, cpc itself significantly increased the platelet membrane fluidity and the cyclic AMP level through inhibiting cyclic AMP phosphodiesterase activity. These findings strongly demonstrate that cpc is an inhibitor of platelet aggregation, which may be associated with mechanisms including inhibition of thromboxane A2 formation, intracellular calcium mobilization and platelet surface glycoprotein IIb/IIIa expression accompanied by increasing cyclic AMP formation and platelet membrane fluidity.
Department of Pharmacology, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China.
Hui-Fen
HF
Chiu
Shih-Ping
SP
Yang
Yu-Ling
YL
Kuo
Yuan-Shu
YS
Lai
Tz-Chong
TC
Chou
D000818:Animals; D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D010798:Phycocyanin / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011817:Rabbits; D013929:Thromboxane B2 / Q000096:biosynthesis; D013930:Thromboxane-A Synthase / Q000378:metabolism
D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D010798:Phycocyanin; D013929:Thromboxane B2; D000242:Cyclic AMP; D011451:Prostaglandin-Endoperoxide Synthases; D013930:Thromboxane-A Synthase; D006152:Cyclic GMP; D002118:Calcium