thromboxane-b2 and tanshinone

Tanshinone IIA (STS), an active ingredient of the Chinese herb Danshen (Salvia miltiorrhiza) for angina and stroke in adults, has been reported to inhibit platelet function. However, its effect on platelet and underlying mechanism remain largely unknown, particularly in neonates.. To investigate the effect of STS on the platelet aggregation and its interaction with various platelet activation pathways, platelet aggregatory function was studied in whole blood stimulated by collagen (2-10 μg/ml) ex vivo in newborn piglets receiving intravenous STS (0.1-10mg/kg, n=8) and in vitro in whole blood from newborn piglets (n=6) incubated with STS (0.1-100 μg/ml). The respective morphological changes of platelets were also examined by scanning electron microscopy. Plasma levels of nitrite/nitrate (NOx) and thromboxane B(2) (TxB(2)), matrix metalloproteinase (MMP)-2 and -9 activities were also examined. To further delineate the mechanistic pathway, the effect of STS on endothelial microparticles release from cultured human umbilical vein endothelial cells (HUVECs) was quantified by flow cytometry.. STS impaired the ex vivo, but not in vitro, collagen-stimulated platelet aggregation. Infusion of STS elevated the plasma level of TxB(2) at 10mg/kg. However, STS had no effect on NOx level. Incubating cultured HUVECs with STS (1 and 10 μg/ml) caused a significant release of endothelial microparticles. Morphologically, STS elicited platelet activation in vivo, but not in vitro.. STS impairs the ex vivo whole blood platelet aggregatory function by activating platelet in vivo in healthy newborn piglets. It implies that STS may elicit its effects by stimulating endothelial microparticles production and eicosanoid metabolism pathway.

Topics: Abietanes; Animals; Animals, Newborn; Blood Platelets; Cell-Derived Microparticles; Cells, Cultured; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Flow Cytometry; Human Umbilical Vein Endothelial Cells; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Microscopy, Electron, Scanning; Nitrates; Nitrites; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Salvia miltiorrhiza; Swine; Thromboxane B2