Novel Bioactivity of Ellagic Acid in Inhibiting Human Platelet Activation

Yi Chang,Cheng-Ying Hsieh,Duen-Suey Chou,Chao-Chien Chang,Li-Jyun Lin,Kuan-Hung Lin,Wei-Fan Chen,Joen-Rong Sheu

doi:10.1155/2013/595128

Abstract

Pomegranates are widely consumed either as fresh fruit or in beverage form as juice and wine. Ellagic acid possesses potent antioxidative properties; it is known to be an effective phytotherapeutic agent with antimutagenic and anticarcinogenic qualities. Ellagic acid (20 to 80 μM) exhibited a potent activity in inhibiting platelet aggregation stimulated by collagen; however, it did not inhibit platelet aggregation stimulated by thrombin, arachidonic acid, or U46619. Treatment with ellagic acid (50 and 80 μM) significantly inhibited platelet activation stimulated by collagen; this alteration was accompanied by the inhibition of relative [Ca2+]i mobilization, and the phosphorylation of phospholipase C (PLC)γ2, protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and Akt, as well as hydroxyl radical (OH●) formation. In addition, ellagic acid also inhibited p38 MAPK and Akt phosphorylation stimulated by hydrogen peroxide. By contrast, ellagic acid did not significantly affect PKC activation and platelet aggregation stimulated by PDBu. This study is the first to show that, in addition to being considered a possible agent for preventing tumor growth, ellagic acid possesses potent antiplatelet properties. It appears to initially inhibit the PLCγ2-PKC cascade and/or hydroxyl radical formation, followed by decreased phosphorylation of MAPKs and Akt, ultimately inhibiting platelet aggregation.

Highlights

Epidemiological studies have shown that an inverse relationship exists between diets rich in fruits, vegetables, and spices and the risk of all causes of death from cancer and cardiovascular diseases (CVD) [1]
The 50% inhibitory concentration (IC50) value of ellagic acid for platelet aggregation induced by collagen was approximately 50 μM (Figure 1(b))
When platelets were preincubated with ellagic acid at a higher concentration of 120 μM or 0.5% dimethyl sulfoxide (DMSO) for 10 min, followed by 2 washes with Tyrode’s solution, there were no significant differences between the aggregation curves of either platelet preparation stimulated by collagen (1 μg/mL), indicating that the effect of ellagic acid in inhibiting platelet aggregation occurred in a reversible p-p47 α-Tubulin p47 phosphorylation p-p47 α-Tubulin p47 phosphorylation and noncytotoxic manner

Summary

Introduction

Epidemiological studies have shown that an inverse relationship exists between diets rich in fruits, vegetables, and spices and the risk of all causes of death from cancer and cardiovascular diseases (CVD) [1]. Fresh and processed fruits and food products contain high levels of a diverse range of phytochemicals of which polyphenols including hydrolyzable tannins (ellagitannins (ETs) and gallotannins) and condensed tannins (proanthocyanidins), anthocyanins, and other flavonoids make up a large proportion [2]. Commercial pomegranate juice contains high levels of polyphenols, including ellagic acid in its free (Figure 1(a)) and bound forms (such as ETs and ellagic acid glycosides), gallotannins, anthocyanins (cyanidin, delphinidin, and pelargonidin glycosides), and other flavonoids [2, 3]. Follow-up studies have shown that ellagic acid is an effective phytotherapeutic agent that exerts antimutagenic and anticarcinogenic effects through diverse cellular mechanisms. These include the induction of cell cycle arrest

Methods

Results

Conclusion