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Abstract
Salvianolic acid A (SAA), the water-soluble phenolic acids in Salvia miltiorrhiza,
has shown the most potent bioactivities, including protection against cerebral lesion,
defense from oxidative damage and improvement of remembrance. In the present study,
we studied the antiplatelet and antithrombotic effects of a newly synthesized SAA
with different methods both in vitro and in vivo.
We tested the effect of antithrombotic activity of SAA in arterio-venous shunt model.
The effects of SAA on adenosine diphosphate (ADP)-, Thrombin-, Arachidonic acid- induced
rat platelets aggregation were tested both in vivo and in vitro. The activity of SAA
on washed human platelet aggregation was determined by ADP stimulation. We also evaluated
its property of modulation of hemorheology, assessed its bleeding side effect by measuring
coagulation parameters after intravenous administration for 5 days and investigated
the potential mechanisms underlying such activities.
In vivo, SAA significantly reduced thrombus weight in the model of arterio-venous
shunt. Meanwhile, SAA increased plasma cAMP level determined by radioimmunoassay in
the same model. Intravenously administrated SAA (2.5-10 mg/kg) inhibited platelet
aggregation induced by ADP in a dose-dependent manner. Notably, SAA did not affect
coagulation parameters in rats after intravenous administration SAA for successive
5 days. In vitro, pretreatment with SAA on washed rat and human platelets significantly
inhibited various agonists stimulated platelet aggregation and caused an increase
in cAMP level in platelets activated by ADP. These findings support our hypothesis
that SAA possesses antithrombotic activities. The antithrombotic effect might be related
to its antiplatelet action and ability to modulate hemorheology without affecting
coagulation system. The mechanisms underlying such activities may involve the induction
of cAMP.
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