Cordycepin (3'-deoxyadenosine), which comes from Cordyceps militaris, the Chinese medicinal fungal genus Cordyceps, is known to have anti-tumour activity. In this study, we investigated the novel effect of cordycepin on human platelet aggregation that was induced by U46619, a thromboxane A(2) (TXA(2)) analogue. TXA(2) is an aggregation-inducing autacoidal molecule that is produced in various agonist-activated platelets. Cordycepin completely inhibited U46619-induced platelet aggregation and simultaneously reduced cytosolic free Ca(2+) ([Ca(2+)](i)), which was increased by U46619 (5 microM) up to 66%. Furthermore, the U46619-stimulated phosphorylation of Ca(2+)-dependent proteins (20 kDa of a myosin light chain and 47 kDa of pleckstrin) was strongly inhibited by cordycepin. These results suggest that cordycepin may have a beneficial effect on autacoidal TXA(2)-mediated thrombotic diseases by inhibiting TXA(2)-induced platelet aggregation via suppression of the Ca(2+) level.

Patients with type 2 diabetes mellitus have increased risk of cardiovascular disease. Epidemiological studies have shown a correlation between diet and incidence of coronary heart disease. The aim of the study is to determine the effect of a traditional Greek Mediterranean diet on platelet aggregation induced by ADP, arachidonic acid (AA), and especially platelet-activating factor (PAF) on patients with type 2 diabetes mellitus as well as on healthy volunteers. The patients were randomized into two subgroups, A and B. The lipid extracts from traditional Greek Mediterranean-type meals were tested in in vivo for their ability to reduce PAF- or thrombin-induced platelet aggregation. The meals with the most potent anti-aggregating activity were chosen for the diet of both subgroup A and healthy subjects and consumed for a period of 28 days, whereas subgroup B kept to their regular diet that was followed before entering the study. Platelet-rich plasma was isolated before and after the diet, and the ability of platelets to aggregate under the aggregating factors was tested. One-month consumption of diet resulted in a significant reduction in PAF- and ADP-induced aggregation of platelets in both groups of healthy volunteers (PAF and ADP, P<.05) and subgroup A (PAF, P<.001; ADP, P<.05), whereas the AA-induced aggregation was not affected. No effect was observed in subgroup B, which followed the standard diet. Thus the consumption of a traditional Greek Mediterranean diet even for a short period can reduce platelet activity in patients suffering from type 2 diabetes mellitus and in healthy subjects.

INTRODUCTION: The phenolic compounds of olive leaves and olive oils in the Mediterranean diet have been associated with a reduced incidence of heart disease. Accordingly, antioxidant-rich diets may prevent the deleterious effects of oxidative metabolism by scavenging free radicals, thus inhibiting oxidation and delaying atherosclerosis. The process involves phospholipase C activation and arachidonic acid metabolism, and is thought to reduce hydrogen peroxide (H(2)O(2)). In our study, an extract of Olea europaea L. leaves was used. The active phenolic compounds in this extract are part of the secoiridoid family, known for their capacity to scavenge H(2)O(2). The results from this study will help to improve our understanding of effects of polyphenol antioxidants in olive leaf extract on platelet function.

METHODS: Full blood examination (FBE), platelet aggregation, and ATP release were performed on samples from fasting, normal, healthy male subjects. Platelet function at increasing concentrations of oleuropein was investigated through measures of platelet aggregation and ATP release from activated platelets.

RESULTS: Blood analysis (n=11) revealed a significant dose-dependant reduction in platelet activity with olive extract concentrations of 1.0% v/v (P<0.001). ATP Release showed a similar pattern (P=0.02).

CONCLUSIONS: Olive leaf polyphenols derived from O. europaea L. leaves inhibited in vitro platelet activation in healthy, non-smoking males. Further bioavailability studies need to be undertaken to determine the in vivo effect of extract on platelet function and to validate the present results.