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Biochimica et Biophysica Acta - General Subjects 1995-Sep

Inhibition on platelet activation by shikonin derivatives isolated from Arnebia euchroma.

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F N Ko
Y S Lee
S C Kuo
Y S Chang
C M Teng

关键词

抽象

Acetylshikonin, teracrylshikonin, beta,beta-dimethylacrylshikonin and shikonin, isolated from Arnebia euchroma, inhibited collagen (10 micrograms/ml)-induced aggregation of washed rabbit platelets in a concentration-dependent manner with IC50 values of 2.1 +/- 0.2, 2.8 +/- 0.3, 4.2 +/- 0.5 and 10.7 +/- 0.7 microM, respectively. Acetylshikonin also inhibited the aggregation and ATP release of washed rabbit platelets induced by arachidonic acid (AA, 100 microM), U46619 (1 microM), platelet-activating factor (PAF, 3.6 nM) and thrombin (0.1 U/ml) in a concentration-dependent manner. The IC50 values of acetylshikonin on the inhibition of these four agonists-induced platelet aggregation were 3.1 +/- 0.4, 2.2 +/- 0.2, 8.0 +/- 0.6 and 12.7 +/- 1.0 microM, respectively. The thromboxane B2 formation caused by collagen, PAF and thrombin was inhibited by acetylshikonin, while formations of thromboxane B2 and prostaglandin D2 caused by AA were not inhibited. Acetylshikonin did not inhibit cyclooxygenase activity since it did not attenuate prostaglandin E2 formation after incubation of sheep vesicular gland microsomes with AA. Acetylshikonin suppressed both the rise of intracellular Ca2+ concentration and the generation of [3H]inositol monophosphate caused by these five aggregation inducers. Platelet cyclic AMP level was unaffected by acetylshikonin. These data indicate that acetylshikonin inhibits platelet activation by suppression of phosphoinositide breakdown.

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