Z-ligustilide Extracted from Radix Angelica Sinensis Decreased Platelet Aggregation Induced by ADP Ex Vivo and Arterio-venous Shunt Thrombosis In Vivo in Rats

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Antithrombotic therapy has become an important goal for the treatment of ischemic disorders such as cerebral ischemia. Our recent studies found that Z-ligustilide (LIG), a characterized 3-n-alkylphthalide constituent of Radix Angelica sinensis essential oil, exerted significant neuroprotection against cerebral ischemic damage in several animal models. The present study evaluated the antithrombotic activity of LIG and its effect on platelet aggregation and coagulation time. LIG (10 or 40 mg/kg) was intragastrically administered to rats once daily for 3 days. Our results showed that LIG significantly and dose-dependently reduced arterial thrombus weight in an arteriovenous shunt thrombosis in rats and platelet aggregation induced by adenosine diphosphate in rats ex vivo. Meanwhile, LIG at 10 or 40 mg/kg had no significant effect on coagulation time, including activated partial thromboplastin time and prothrombin time, in rats ex vivo. The present study demonstrated for the first time that LIG may exert efficient antithrombotic activity through inhibition of platelet aggregation, without effecting coagulation time of peripheral blood. These data, together with the previously reported neuroprotective effects of LIG on cerebral ischemia, suggest that the antithrombotic activity of LIG may contribute to its potential for the treatment of ischemic diseases, including ischemic stroke.