British Journal of Nutrition

Full Papers

Inhibition of platelet aggregation by olive oil phenols via cAMP-phosphodiesterase

Mario Dell'Aglia1 c1, Omar Maschia1, Germana V. Gallia1, Rossana Fagnania1, Esther Dal Ceroa1, Donatella Carusoa1 and Enrica Bosisioa1

a1 Research centre for the characterization and safe use of natural compounds-‘Giovanni Galli’, Department of Pharmacological Sciences, University of Milan, Italy


The aim of the present study was to confirm that olive oil phenols reduce human platelet aggregability and to verify the hypothesis that cAMP- and cGMP- phosphodiesterases (PDE) could be one of the targets of the biological effect. Four extracts from oils characterized by a high phenol content (HPE), and low phenol levels (LPE) were prepared and analyzed quali- and quantitatively by HPLC-UV and electrospray ionization–MS/MS. Human washed platelets stimulated with thrombin were used for the aggregation assay. Human platelet cAMP-PDE and recombinant PDE5A1 were used as enzyme source. Platelet aggregation and enzyme activity were assayed in the presence of HPE, LPE and individual phenols. The phenol content of HPE ranged between 250 and 500 mg/kg, whereas the LPE content was 46 mg/kg. The compounds identified were hydroxytyrosol (HT), tyrosol (TY), oleuropein aglycone (OleA) and the flavonoids quercetin (QU), luteolin (LU) and apigenin (AP). OleA was the most abundant phenol (range 23·3 to 37·7 %) and LU was the most abundant flavonoid in the extracts. Oil extracts inhibited platelet aggregation with an 50% inhibitory concentration interval of 1·23–11·2 μg/ml. The inhibitory effect of individual compounds (10 μm) including homovanillyl alcohol (HVA) followed this order: OleA>LU>HT = TY = QU = HVA, while AP was inactive. All the extracts inhibited cAMP-PDE, while no significant inhibition of PDE5A1 (50μg/ml) was observed. All the flavonoids and OleA inhibited cAMP-PDE, whereas HT, TY, HVA (100 μm) were inactive. Olive oil extracts and part of its phenolic constituents inhibit platelet aggregation; cAMP-PDE inhibition is one mechanism through which olive oil phenols inhibit platelet aggregation.

(Received May 23 2007)

(Revised August 08 2007)

(Accepted August 24 2007)

(Online publication October 11 2007)


c1 Corresponding author: Dr Mario Dell'Agli, fax +39-0250318391, email


Abbreviations: AP, apigenin; ESI, electrospray ionisation; HPE, high phenol extract; HT, hydroxytyrosol; HVA, homovanillyl alcohol; IC50, concentration that reduces the effect by 50 %; LPE, low phenol extract; LU, luteolin; OleA, oleuropein aglycone; PDE, phosphodiesterase; QU, quercetin; TY, tyrosol