Antithrombotic effect of rutaecarpine, an alkaloid isolated from Evodia rutaecarpa, on platelet plug formation in in vivo experiments

• Published in: British journal of haematology 2000-07, Vol.110 (1), p.110-115
• Main Authors: Sheu, J. R., Hung, W. C., Wu, C. H., Lee, Y. M., Yen, M. H.
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate; Alkaloids - pharmacology; Animals; arterial thrombosis; Aspirin - pharmacology; Biological and medical sciences; Bleeding Time; Blood Pressure - drug effects; Blood. Blood coagulation. Reticuloendothelial system; Drugs, Chinese Herbal; Fluorescein; fluorescein sodium; Hematology; Indole Alkaloids; Medical sciences; Mice; Mice, Inbred ICR; occlusion time; Pharmacology. Drug treatments; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - pharmacology; platelet plug; Pulmonary Embolism - drug therapy; Quinazolines; Rats; Rats, Sprague-Dawley; rutaecarpine
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2000.01953.x

In this study, platelet thrombi formation was induced by irradiation of mesenteric venules with filtered light in mice pretreated intravenously with fluorescein sodium. Rutaecarpine (200 µg/g) significantly prolonged the latent period of inducing platelet plug formation in mesenteric venules when it was intravenously injected. Rutaecarpine (200 µg/g) prolonged occlusion time by approximately 1·5‐fold (control 127 ± 29 vs. taecarpine 188 ± 23 s). Furthermore, aspirin (250 µg/g) also showed a similar prolongation of the occlusion time in this experiment. On a molar basis, rutaecarpine was approximately twofold more potent than aspirin at prolonging the occlusion time. Furthermore, rutaecarpine was also effective in reducing the mortality of ADP‐induced acute pulmonary thromboembolism in mice when administered intravenously at doses of 25 and 50 µg/g. Intravenous injection of rutaecarpine (50 µg/g) significantly prolonged the bleeding time by approximately 1·5‐fold compared with normal saline in the severed mesenteric arteries of rats. Continuous infusion of rutaecarpine (5 µg/g/min) also significantly increased the bleeding time 1·5‐fold, and the bleeding time returned to baseline within 60 min after cessation of rutaecarpine infusion. These results suggest that rutaecarpine has an effective anti‐platelet effect in vivo and that it may be a potential therapeutic agent for arterial thrombosis, but it must be assessed further for toxicity.