Flavonoids platelet aggregation inhibited

The unusual flavonoid derivative kuwanon G, 30, is reported to lower blood pressure in rabbits when administered intravenously at a dose of l.Omg/kg of body weight (743). (-h)-Catechin [(-h)-cyanidan-3)ff-ol], 31, is remarkably bioactive. Among its recently reported biological effects are the following antianaphylactic (517), anticoagulant (569), antihepatotoxic (963), platelet aggregation inhibition (118), and serotonin secretion inhibition (100) effects. 

Freedman and others (2001) determined the effects of purple grape juice and its main flavonoids on the functionality of platelets and the production of NO. They observed that incubation of platelets with diluted grape juice resulted in the inhibition of aggregation, increased production of NO, and decreased production of superoxide. To confirm the relevance of these findings, 20 healthy subjects were supplemented with 7 mL of black grape juice/kg/day for 14 days. The inhibition of platelet aggregation was also observed ex vivo there was an increase in the production of NO from 3.5 1.2 to 6.0 1.5 pmol/108 platelets and a decrease in the release of superoxide, from 29.5 5.0 to 19.2 3.1 arbitrary units. Under these conditions the antioxidant capacity of protein-free plasma increased by 50% (Freedman and others 2001). 

Some polyphenols inhibit platelet aggregation reducing the risk of thrombosis [171-173]. This effect may be due to a series of interaction of flavonoids in different biochemical pathways, such as by inhibition of cyclooxygenase and lipoxygenase, that are involved in the arachidonic acid metabolism in the platelets, or by inhibition of the formation of tromboxane and of the receptor function of the same [173-176]. Regular consumption of wine, tea and chocolate has been associated to the reduction of platelet aggregation, cardio-vascular diseases and thrombosis [171,177-179]. 

The degree of inhibition is dependent on the type of inducer and on the structure of the flavonoid. At 30 pM, fisetin, kaempferol or quercetin inhibit the platelet aggregation induced by arachidonic acid, whereas morin and myricetin are effective only at concentrations greater than 150 pM... 

Several mechanisms have been implicated on the inhibition of platelet aggregation induced by flavonoids ... 

A) Inhibition of platelet phosphodiesterases (PDEs) [91]. Quercetin and myricetin potentiated the anti-aggregatory action of prostacyclin (PGI2), a potent stimulator of platelet adenylate cyclase synthesised by the vascular endothelium, on ADP-induced platelet aggregation in washed human platelets, and the elevation of platelet cyclic adenosine monophosphate (cAMP) elicited by PGI2 [89,92,93]. These effects are probably due to an inhibition of PDEs. As suggested by Ferrell and co-workers [92], this inhibition arises from the similarity between the pyranone ring of flavonoids and the pyrimidine ring of adenine. 

C) Inhibition of cyclic nucleotide PDEs. Elevation in cellular cyclic nucleotides induces vascular smooth muscle relaxation [132]. The cellular accumulation of cAMP and cGMP depends upon the rate of their synthesis and their breakdown. The latter is achieved by cyclic nucleotide PDEs that have been classified into seven families [133]. Some flavonoids (apigenin, kaempferol, fisetin and quercetin) produce an inhibitory action on cyclic nucleotide PDEs [134,135] which may collaborate in the inhibitory effect on platelet aggregation [93] and vascular smooth muscle relaxation... 

Trans-resveratrol (trans-3,5,4 -trihydroxystilbene) is a non-flavonoid polyphenol found in grapes, mulberries, and other food prod-ucts. It is responsible for the antioxidant activity of red wine. Intake of moderate amount of red wine has been found to reduce the risk of cardiovascular diseases. In addition to antioxidant activity, resveratrol could inhibit platelet aggregation, and showed anticancer activity. The phenoxyl radicals of resveratrol produced during oxidation by hydroxyl radicals, one-electron oxidants, and peroxyl radicals showed absorption maximum at 410 nm (Fig. I). Reports indicate that trans-resveratrol is a better radical scavenger than vitamins E and C and its activity is similar to that of the flavonoids epicatechin and quercetin. From the comparison of the spectral and kinetic properties of the transients derived from trans-resveratrol and its analogues, it could be concluded that in the neutral and acidic solutions, the para-hydroxy... 

Several cohort studies have been performed in which the relationships between flavonoid intake and the risk of coronary heart disease have been investigated. The studies have shown that the mortality from coronary heart diseases (CHD) is inversely correlated with the intake of flavonoids in the diet. Hollman and Katan (1998) summarize that in three out of five cohort studies, in addition to one cross-cultural study, flavonoids from the flavonol and flavone subgroups demonstrated a protective role toward cardiovascular disease. The protective effect of the flavonoids is partly explained by the inhibition of LDL oxidation and by reduced platelet aggregability. As reviewed by Cook and Samman (1996), there are several possible routes as to how LDL is oxidized by free radicals generated in the cells and how the oxidized LDL initiates and promotes atherosclerosis in the human body. 

The numerous health related properties of flavonoids, widely described in epidemiological studies, are mainly based on their antioxidant activities. These properties have been found to include anti-inflammatory and antiviral activities, effects on capillary fragility, inhibition of human platelet aggregation and anticancer activity. The antioxidant capacity of any flavonoid will be determined by a combination of the catechol structure in the B-ring, the 2,3-double bond in conjunction with a 4-oxo function, and the presence of both hydroxyl groups in positions 3 and 5. Due to their... 

Chamomile has been indicated as an herb with the theoretical potential for interacting with warfarin due to the coumarin content of the herb (Heck et al. 2000). The cou-marin content, however, consists of the coumarin derivatives herniarin and umbelliferone. Herniarin has been shown to have hemostatic activity (Ahmad and Misra 1997) and umbelliferone has shown no evidence of anticoagulant activity (Egan et al. 1990 Feuer 1974 Pelkonen et al. 1997). The flavonoid apigenin has been shown to inhibit platelet aggregation in vitro (Landolfi et al. 1984 Teng et al. 1985). 

Hemostatic and mild hypotensive activities have been reported (bradly). In an in vitro study, the aqueous extract of U. dioica dose dependently inhibited thrombin-induced platelet aggregation. The observed effect has been attributed to the flavonoid constituents of the extract. The hypotensive effects of U. dioica extracts (aqueous and methanohc, in vivo and in isolated organs) have also been reported by more than one group and the mechanism of action is suggested to be through vasodilation mediated by nitric oxide release, potassium channel opening, and negative inotropic action. ... 

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