Nutrition Phytochemicals Affecting Platelet Signaling and Responsiveness: Implications for Thrombosis and Hemostasis

Abstract

Cardiovascular disease, in particular due to arterial thrombosis, is a leading cause of mortality and morbidity, with crucial roles of platelets in thrombus formation. For multiple plant-derived phytochemicals found in common dietary components, claims have been made regarding cardiovascular health and antiplatelet activities. Here we present a systematic overview of the published effects of common phytochemicals, applied in vitro or in nutritional intervention studies, on agonist-induced platelet activation properties and platelet signaling pathways. Comparing the phytochemical effects per structural class, we included general phenols: curcuminoids (e.g., curcumin), lignans (honokiol, silybin), phenolic acids (caffeic and chlorogenic acid), derivatives of these (shikimic acid) and stilbenoids (isorhapontigenin, resveratrol). Furthermore, we evaluated the flavonoid polyphenols, including anthocyanidins (delphinidin, malvidin), flavan-3-ols (catechins), flavanones (hesperidin), flavones (apigenin, nobiletin), flavonols (kaempferol, myricetin, quercetin), isoflavones (daidzein, genistein); and terpenoids including carotenes and limonene; and finally miscellaneous compounds like betalains, indoles, organosulfides (diallyl trisulfide) and phytosterols. We furthermore discuss the implications for selected phytochemicals to interfere in thrombosis and hemostasis, indicating their possible clinical relevance. Lastly, we provide guidance on which compounds are of interest for further platelet-related research.

The Anti-Inflammatory and Antithrombotic Properties of Bioactives from Orange, Sanguine and Clementine Juices and from Their Remaining By-Products

“…The anti-platelet effect of flavonoids found in citrus fruits and their peels, such as hesperetin, hesperidin, and naringin, has been previously reported against other pathways of platelet activation involving collagen, arachidonic acid, and the decrease in TXB2 formation, ADP release and granule secretion [13][14][15]19,38]. In addition, naringenin, the aglycon analog of naringin, along with quercetin, have both been shown to antagonistically inhibit the inflammatory PAF-pathway with an IC 50 value similar to the ones for the fractions of phenolic compounds of oranges and mandarins-clementines, observed in the present study [39].…”

“…Such flavonoids are also present in high amounts in orange peel, which is the primary waste fraction in the production of orange juice. It has been proposed that supplementation with such flavonoids found in orange peel extracts may be beneficial only when the body is under severe oxidative stress and when supplementation is given over time and not as a single administration [38].…”

“…Another bioactive fraction with strong anti-PAF properties was the peels' TL fraction of terpenoids. Citrus fruits' peel oils are rich in terpenoids and especially in monoterpenes such as limonoids and limonenes [36], which have previously been reported that possess strong anti-oxidant properties and activities anti-platelet effects [38]. Terpenoids from other sources, such as the ginkgolides from the Ginkgo biloba tree, are classic PAF-antagonists, which may explain why the terpenoids' fraction of citrus fruits peels, but also those of citrus fruits juices, also have strong anti-PAF potential.…”

Isolation and Characterization of a New Flavone C-glycoside Isoembinin from Iris lacteal along with its Effects on Platelet Activation

“…Crl -control, Thr -thrombin, Apiapigenin. Data are presented as means ± SD, (one-way ANOVA, Leven's test p>0.05 followed by Tukey's HSD test), + -p < 0.05 compared to thrombin sample which was designated as 100%, n = 6. , immunomodulatory [10], antiinflammatory [11], anticancer [12], antidiabetic [13] and antithrombotic [14][15] activities have been described. Flavonoids also play a significant role in the protection from cardiovascular diseases, the leading causes of mortality and morbidity…”

“…About 50% of all pharmaceutical drugs are produced on the basis of natural compounds isolated from different plants [8]. Throughout the literature, the beneficial effects of flavonoids, including both C-and O-glycosides, such as antioxidant [9], immunomodulatory [10], antiinflammatory [11], anticancer [12], antidiabetic [13] and antithrombotic [14][15] activities have been described. Flavonoids also play a significant role in the protection from cardiovascular diseases, the leading causes of mortality and morbidity…”