Crocetin is a natural carotenoid dicarboxylic acid that is found in the fruit of Gardenia jasminoides Ellis (Cape Jasmine) and in the stamen and pistil of Crocus sativus L. (saffron). It is used worldwide as an important spice, food colorant, and herbal medicine. In the current investigation, we have examined the cardiovascular effects of crocetin using stroke-prone spontaneously hypertensive rats (SHRSPs). Male SHRSPs (6 weeks old) were classified into three groups: a control group and two crocetin groups (25 and 50 mg/kg/day). The animals were given crocetin for 3 weeks. Body weights in each group were not significantly different during the treatment period, but the increase in systolic blood pressures observed with age was significantly moderated by crocetin. Thrombogenesis, assessed using a He-Ne laser technique in pial vessels, was significantly decreased. Antioxidant activity, assessed by measuring urinary 8-hydroxy-2'-deoxyguanosine levels, together with urinary nitric oxide (NO) metabolite levels, was increased significantly after treatment. Acetylcholine-induced vasodilation was measured using the aorta and indicated that endothelial function was significantly improved by crocetin. These results strongly suggest that the antihypertensive and antithrombotic effects of crocetin were related to an increase in bioavailable NO, possibly mediated by decreased inactivation of NO by reactive oxygen species.
Prevention of arterial thrombotic diseases has a high priority in developed countries. An inappropriate diet is known to enhance the risks for acute thrombotic events, and nutritional products experimentally shown to be antithrombotic, might contribute beneficial effects. The present study forms part of a series of investigations into the antithrombotic effect of various foods and vegetables. Roasted and crushed whole grains from six varieties of sesame seeds were added to the diet of mice. Antithrombotic activity was measured in the carotid artery in vivo, using a He-Ne laser-induced thrombosis technique after 12 weeks. Col/Chichibu/Maruteru-2/1995 and T016 varieties showed significant antithrombotic activity, whilst 00037803 was prothrombotic. The acute effects of purified ingredients, sesamin, sesamolin and sesamol, given orally or intra-arterially, were also examined after a single dose. The most effective ingredient was sesamol, followed by sesamolin and sesamin. Daily intake of specific antithrombotic sesame whole grains or purified active ingredients might help to prevent atherothrombotic diseases.
Background and Objectives Atherosclerosis is characterized by a hypercoagulable state, during which coagulation and fibrinolytic factors are activated simultaneously. However, details regarding the thrombolytic pathway in this context remain unknown. Here we investigated how direct long-term inhibition of thrombin influenced spontaneous thrombolytic activity during atherosclerotic progression in apolipoprotein E (ApoE) – / – –low density lipoprotein receptor (LDLR) – / – double-knockout mice. Methods All mice received either standard chow (placebo group) or dabigatran-containing chow for 22 weeks, after which we evaluated them. The amount of atherosclerosis was estimated as the ratio of the atherosclerotic area to the total aortic intimal area. In addition, we used immunohistochemistry to analyze the expression of tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), and endothelial nitric oxide synthase (eNOS) in atherosclerotic regions. To evaluate thrombolysis, we used a He–Ne laser to induce thrombosis in vessels of the cremaster muscle and then measured the thrombus volume over time. Results The atherosclerotic area was smaller and thrombolytic activity greater in the dabigatran-treated group than in the placebo group. Furthermore, according to the thrombolysis model, spontaneous thrombolytic activity was increased in the dabigatran-treated mice compared with the placebo mice. In support of these results, immunohistochemistry demonstrated decreased expression of PAI-1 and TAFI but increased expression of eNOS in the dabigatran group compared with the placebo group. However, t-PA expression did not differ between groups. Conclusions Direct long-term inhibition by dabigatran etexilate of thrombin led to an increase in spontaneous thrombolytic activity decreasing the expression of PAI-1 and TAFI.
The prevention of arterial thrombotic disease has a high priority in developed countries. An inappropriate diet is known to enhance the risk for acute thrombotic events, and a regular diet with proven antithrombotic effects might be a beneficial way to prevent disease. The present study was undertaken as part of a series of in-vestigations to examine various vegetables and fruits for antithrombotic activity, and to add to the previously reported data on different onion varieties produced in the northern part of Japan (Hokkaido). For this purpose, a sophisticated method to assess shear-induced platelet reac-tivity/thrombolysis in vitro (The Global Throm-bosis Test, GTT) was used to screen 5 different varieties of onion produced in the middle part of Japan (Awaji Island). The different onion varie-ties demonstrated a variable effect on thrombo-sis, and one particular variety, designated ONA-03, appeared to exert an antithrombotic effect. Another variety, ONA-01, appeared to have prothrombotic activity by inhibiting spon-taneous thrombolytic activity. The especially effective variety was further investigated using an in vivo, laser-induced thrombosis model in mice. The heat stable antithrombotic activity in vitro and in vivo was demonstrated to be due to antiplatelet activity. The present findings added to the list of antithrombotic fruits and vegeta-bles
The prevention of arterial thrombotic disease has a high priority in developed countries. We have focused our studies on the antithrombotic activity of those fruits and vegetables with the potential to prevent the disease, and the present study was undertaken as part of a series of investigations to examine beneficial fruits and vegetables. For this purpose, suitable laboratory tests as well as diets have been devised. In the current investigation, we have classified various tomato varieties with antithrombotic properties, and we now have extended our overall data to include more than ten antithrombotic varieties of fruits and vegetables. A method designed to measure shear-induced platelet activity (the Global Thrombosis Test, GTT) was used to assess haemostasis in vitro and a He-Ne laser-induced thrombosis technique was utilized to examine arterial thrombogenesis in vivo. Concentrations of the antioxidant, lycopene, were also measured. Three mini-type tomato varieties, coded “Cin”, “Pik” and “Caec”, and one mediumtype variety, coded “K”, were harvested at different stages of maturity. All mini-type varieties demonstrated antithrombotic activity at an early (green) stage. The antithrombotic activity decreased with the maturation of “Cin” and “Caec” but remained constant at all stages of maturity with “Pik”. The medium variety, “K”, did not possess antithrombotic activity. Lycopene was not detected at any stage in any of the tomato varieties, suggesting that this antioxidant did not contribute to antithrombotic activity. The present results indicated that the antithrombotic activity of tomatoes is dependent on the particular variety and stage of maturity, and that this activity is not due to lycopene.
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