Preventive effect of a novel diosgenin derivative on arterial and venous thrombosis in vivo

Current therapy for blood vessel thrombosis has the risk of leading to gastrointestinal bleeding and thrombocytopenia. We previously reported that a new derivative of diosgenin, compound 5, had significant anti-inflammatory activity superior to that of aspirin, prolonged bleeding time, and inhibited platelet aggregation in vitro. In the present study, we investigated the in vivo efficacy and safety of compound 5 using the ferric chloride (FeCl3)-induced arterial and venous thrombosis models in rats as well as its toxicity in mice. Compared with the control rats, those treated with compound 5 showed significantly less adenosine diphosphate (ADP)-induced platelet aggregation and a prolonged activated partial thromboplastin time mediated by the specific regulation of factor VIII. Furthermore, compound 5 significantly reduced the average length and weight of thrombi in both arteries and veins. These findings were similar to those of aspirin at the same dose. The safety evaluation revealed a much lower risk of bleeding and lesser gastric mucosal damage with compound 5 than with the same dose of aspirin. An oral dose of up to 575.5 mg/kg showed no toxicity in mice. In conclusion, consistent with our in vitro findings, compound 5 exhibited an in vivo antithrombotic activity that was comparable to aspirin mainly by reducing platelet aggregation and regulating factor VIII, but with fewer side effects.

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