Effect of oleacein, polyphenol of olive oil, with natriuretic peptides on the functions of human neutrophils

Polyphenols of extra virgin olive oil, such as oleacein (3,4-DHPEA-EDA), are believed to play a vital role in the prevention of cardiovascular diseases. It is considered that natriuretic peptides, which amount increase in acute myocardial infarction, exert protective effects against neutrophils- induced endothelial injury. The inhibitory effect of natriuretic peptides, such as atrial (ANP) and brain (BNP), is partly associated with the suppression of functions of neutrophils [1].

Taking into account that NEP is responsible for the degradation of natriuretic peptides, our aim was to establish the effect of oleacein on NEP activity in neutrophils. Additional purpose was to determine the influence of oleacein with or without ANP and BNP (10 ng/mL) on the selected functions of human neutrophils, such as elastase, metalloproteinase 9 (MMP-9), interleukin (IL-8) release from neutrophils.

The determination of NEP activity was performed with spectrofluorimetric method using Suc-L-Ala-L-Ala-Phe-7-amino-3-methyl-coumarin (SAAP-AMC) as a substrate. The inhibition of elastase release were determined using colorimetric method. The effect on MMP-9 and IL-8 production was measured by ELISA assays.

Oleacein inhibited NEP activity (IC₅₀= 43.2 ± 4.0µM). Oleacein in the concentration of 20µM reduced elastase release by 11.0 ± 5.3% (vs. 38.3 ± 5.1% with ANP; 25.4 ± 5.0% with BNP), IL-8 production by 12.9 ± 3.3% (vs. 25.7 ± 2.5% with ANP) and almost did not reduced MMP-9 production (vs. 14.3 ± 4.4% with ANP; 13.5 ± 4.1% with BNP). Unexpectedly oleacein with BNP increased IL-8 production.

Oleacein by inhibiting NEP activity may enhance the protective effects of natriuretic peptides on the endothelium, what may partly explain the role of olive oil in the prevention of cardiovascular diseases.

Reference:

[1] Matsumura, T. et al.; J. Clin. Invest. (1996), 97: 2192 – 2203