INHIBITION ON PLATELET ACTIVATION BY SHIKONIN DERIVATIVES ISOLATED FROM ARNEBIA-EUCHROMA

Acetylshikonin, teracrylshikonin, beta,beta-dimethylacrylshikonin and shikonin, isolated from Amebia euchroma, inhibited collagen (10 mu g/m l)-induced aggregation of washed rabbit platelets in a concentration-d ependent manner with IC50 values of 2.1 +/- 0.2, 2.8 +/- 0.3, 4.2 +/- 0.5 and 10.7 +/- 0.7 mu M, respectively. Acetylshikonin also inhibited the aggregation and ATP release of washed rabbit platelets induced by arachidonic acid (AA, 100 mu M), U46619 (1 mu M), platelet-activating factor (PAF, 3.6 nM) and thrombin (0.1 U/ml) in a concentration-depen dent manner. The IC(5)0 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 mu M, respectively. The thrombo xane B-2 formation caused by collagen, PAF and thrombin was inhibited by acetylshikonin, while formations of thromboxane B-2 and prostagland in D-2 caused by AA were not inhibited. Acetylshikonin did not inhibit cyclooxygenase activity since it did not attenuate prostaglandin E(2) formation after incubation of sheep vesicular gland microsomes with A A. Acetylshikonin suppressed both the rise of intracellular Ca2+ conce ntration and the generation of [H-3]inositol monophosphate caused by t hese five aggregation inducers. Platelet cyclic AMP level was unaffect ed by acetylshikonin. These data indicate that acetylshikonin inhibits platelet activation by suppression of phosphoinositide breakdown.