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

Abstract

Summary. 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 mg/g) significantly prolonged the latent period of inducing platelet plug formation in mesenteric venules when it was intravenously injected. Rutaecarpine (200 mg/g) prolonged occlusion time by approximately 1´5-fold (control 127^29 vs. taecarpine 188^23 s). Furthermore, aspirin (250 mg/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 mg/g. Intravenous injection of rutaecarpine (50 mg/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 mg/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.

The pyrrolidinoindoline alkaloid Psm2 inhibits platelet aggregation and thrombus formation by affecting PI3K/Akt signaling

“…In recent decades, many constituents with biological activities have been isolated from Chinese herbs that have been used as remedies for thousands of years [11] .…”

Rutaecarpine Induces Chloride Secretion across Rat Isolated Distal Colon

“…In addition, Fructus evodiae (fruit of E. rutaecarpa) is also used for the treatment of headache, thoracicoabdominal pain, vomiting, colds, and reduced blood circulation (Fei et al, 2003). Pharmacological studies indicate that Rut has various bioactivities, such as causing vasodilatation by mechanisms of an endothelium-dependent manner coupled with the synthesis or release of nitric oxide (Wang et al, 1996), inhibiting vasoconstriction induced by anaphylaxis (Yu et al, 2005), inducing positive inotropic and chronotropic actions (Kobayashi et al, 2001), protecting the myocardium mediated by calcitonin gene-related peptide (Hu et al, 2002;Yi et al, 2004), increasing intracellular Ca 2ϩ concentration in endothelium (Wang et al, 1996), suppressing platelet plug formation in mesenteric venules (Sheu et al, 2000), inhibiting prostaglandin production in RAW264.7 macrophages (Woo et al, 2001), relaxation of rabbit and human internal anal sphincter (Jiang et al, 2000), gastroprotective effect against injury induced by aspirin and stress (Wang et al, 2005), anti-Helicobacter pylori (Tominaga et al, 2002), blockade of delayed rectifier K ϩ current in NG108-15 neuronal cells (Wu et al, 2001), inhibiting cytochrome P450 in human liver microsomes (Ueng et al, 2002(Ueng et al, , 2006Iwata et al, 2005), and inhibition of COX-2 (Moon et al, 1999).…”

Goshuyuto, a Traditional Japanese Medicine for Migraine, Inhibits Platelet Aggregation in Guinea-Pig Whole Blood

“…In the future, we will investigate the antiaggregatory mechanism of goshuyuto in detail. It has been reported that rutaecarpine, one of the components of Evodiae Fructus, had an inhibitory effect on occlusion time during induced thrombus formation in the mouse (18). In this study, rutaecarpine did not significantly inhibit platelet aggregation at the doses of 100 and 300 μmol / L (data not shown).…”