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Atherosclerosis. 2014 Jan;232(1):17-24. doi: 10.1016/j.atherosclerosis.2013.10.017. Epub 2013 Oct 29.

Hydroxytyrosol suppresses MMP-9 and COX-2 activity and expression in activated human monocytes via PKCα and PKCβ1 inhibition.

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National Research Council (CNR), Institute of Clinical Physiology (IFC), Lecce, Italy.
Department of Biological and Environmental Science and Technologies, University of Salento, Lecce, Italy.
"G. Monasterio" Foundation for Clinical Research, Pisa, Italy; "G. d'Annunzio" University and Center of Excellence on Aging, Chieti, Italy.
National Research Council (CNR), Institute of Clinical Physiology (IFC), Lecce, Italy. Electronic address:



Hydroxytyrosol (HT), the major olive oil antioxidant polyphenol in cardioprotective Mediterranean diets, is endowed with anti-inflammatory and anti-atherosclerotic activity. The production of cyclooxygenase (COX)-2-dependent inflammatory eicosanoids and the functionally linked release of matrix metalloproteinase (MMP)-9 by macrophages likely contribute to plaque instability leading to acute coronary events. Objective of the study was to examine the HT effects on inflammatory markers in human activated monocytes, including MMP-9 and COX-2 activity and expression and explore HT underlying mechanisms.


Human peripheral blood mononuclear cells (PBMC) and U937 monocytes were treated with 1-10 μmol/L HT before activation with phorbol myristate acetate (PMA). HT blunted monocyte matrix invasive potential and reduced MMP-9 release and expression at zymography, ELISA and RT-PCR, with an IC50 = 10 μmol/L ( P< 0.05), without affecting tissue inhibitor of metalloproteinase (TIMP)-1. Moreover, HT inhibited prostaglandin (PG)E2 production and COX-2 expression, without affecting COX-1. These effects were mediated by inhibition of transcription factor nuclear factor (NF)-κB and protein kinase C (PKC)α and PKCβ1 activation.


HT, at nutritionally relevant concentrations, reduces MMP-9 and COX-2 induction in activated human monocytes via PKCα and PKCβ1 inhibition, thus featuring novel anti-inflammatory properties. Overall, such results contribute to explaining the vascular protective effects by olive oil polyphenols in Mediterranean diets.


Cyclooxygenase-2; Hydroxytyrosol; Inflammation; Matrix metalloproteinase-9; Nuclear factor-κB; Oxidative stress; Protein kinase C

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