Antithrombotic effect of rutaecarpine, an alkaloid isolated from Evodia rutaecarpa, on platelet plug formation in in vivo experiments.
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 microg/g) significantly prolonged the latent period of inducing platelet plug formation in mesenteric venules when it was intravenously injected. Rutaecarpine (200 microg/g) prolonged occlusion time by approximately 1.5-fold (control 127 +/- 29 vs. taecarpine 188 +/- 23 s). Furthermore, aspirin (250 microg/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 microg/g. Intravenous injection of rutaecarpine (50 microg/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 microg/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.
Sheu
J R
JR
Graduate Institute of Medical Sciences, Department of Surgery, Taipei Medical College, Taiwan. sheujr@tmc.edu.tw
Hung
W C
WC
Wu
C H
CH
Lee
Y M
YM
Yen
M H
MH
D000244:Adenosine Diphosphate; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001760:Bleeding Time; D001794:Blood Pressure / Q000187:drug effects; D004365:Drugs, Chinese Herbal; D019793:Fluorescein; D026121:Indole Alkaloids; D051379:Mice; D008813:Mice, Inbred ICR; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011655:Pulmonary Embolism / Q000188:drug therapy; D011799:Quinazolines; D051381:Rats; D017207:Rats, Sprague-Dawley; D052999:Quinazolinones
D000244:Adenosine Diphosphate; D000470:Alkaloids; D001241:Aspirin; D004365:Drugs, Chinese Herbal; D019793:Fluorescein; D026121:Indole Alkaloids; D010975:Platelet Aggregation Inhibitors; D011799:Quinazolines; C028632:rutecarpine; D052999:Quinazolinones