From the aqueous extract (Pc) of Petroselinum crispum (Mill) flat leaves specimens were isolated and identified the flavonoids apigenin (1), apigenin-7-O-glucoside or cosmosiin (2), apigenin-7-O-apiosyl-(1→2)-O-glucoside or apiin (3) and the coumarin 2'',3''-dihydroxyfuranocoumarin or oxypeucedanin hydrate (4). The inhibitory activity toward clotting formation and platelet aggregation was assessed for Pc flavonoids (1) and (2), and the coumarin (4). Pc showed no inhibition on clotting activity when compared with the control. On the other hand, a strong antiplatelet aggregation activity was observed for Pc (IC 50 = 1.81 mg/mL), apigenin (IC 50 = 0.036 mg/mL) and cosmosiin (IC 50 = 0.18 mg/mL). In all cases ADP was used as inductor of platelet aggregation. Our results showed that Pc, apigenin and cosmosiin interfere on haemostasis inhibiting platelet aggregation. To the best of our knowledge this is the first report for the cosmosiin antiplatelet aggregation in vitro activity.
1 Envenomation by the snake Bothrops jararaca is typically associated with hemostatic abnormalities including pro-and anticoagulant disturbances. Glycyrrhizin (GL) is a plant-derived thrombin inhibitor that also exhibits in vivo antithrombotic properties. Here, we evaluated the ability of GL to counteract the hemostatic abnormalities promoted by B. jararaca venom. 2 GL inhibited the human fibrinogen clotting (IC 50 ¼ B1.0 mg ml; 0.47 mM) and platelet aggregation (IC 50 ¼ B0.28 mg ml À1 ; 0.33 mM) induced by B. jararaca venom, in vitro. 3 The in vivo effect of GL was tested in rats using a model of venous thrombosis in which intravenous (i.v.) administration of B. jararaca venom (100 mg kg À1 ) produced in all animals a thrombus with a mean weight of 10.671.7 mg. 4 Prior administration of GL (180 mg kg À1 ) or antibothropic serum (27 ml kg À1 ) inhibited thrombus formation by 86 and 67%, respectively. Remarkably, co-administration of ineffective doses of GL and antibothropic serum markedly decreased thrombus weight, suggesting a synergistic effect. 5 Co-administration of GL with antibothropic serum abolished venom-induced bleeding. Ex vivo clotting times showed that rat plasma was non-clotting after i.v. administration of B. jararaca venom. Treatment with GL, antibothropic serum or both before venom administration efficiently prevented this abnormality.6 Altogether, we demonstrate here that GL prevents both in vitro and in vivo venom-induced changes in hemostasis, suggesting a potential antiophidic activity.
Cardiovascular diseases are responsible for the largest number of deaths among humans worldwide, including heart attacks, strokes, and thrombosis. The treatment of thrombosis is generally through the administration of anticoagulant and/or antiplatelet drugs, which have some clinical limitations. Plants synthesize a wide variety of bioactive metabolites in response to different stimuli. This review focuses on a number of molecules of vegetal origin belonging to different chemical classes, with significant anticoagulant and antiplatelet effects. Their promising antithrombotic profile confirms the potential of natural products as a source of lead molecules for drug development in the prevention and treatment of thrombosis.
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