Naturally occurring hydroxytyrosol derivatives: hydroxytyrosyl acetate and 3,4-dihydroxyphenylglycol modulate inflammatory response in murine peritoneal macrophages. Potential utility as new dietary supplements.

This work evaluated the effects of extra virgin olive oil (EVOO) phenols, hydroxytyrosyl acetate (2) and 3,4-dihydroxyphenylglycol (3), as well as two new acyl derivatives of 3, 4-(1,2-di(butanoyloxy)ethyl)benzene-1,2-diol (7) and 4-(1,2-di(lauroyloxy)ethyl)benzene-1,2-diol (8), on LPS-stimulated murine peritoneal macrophages in comparison with hydroxytyrosol (HTy, 1). Compounds 2, 3, 7, and 8 showed a strong reactive oxygen species (ROS)-scavenging activity, reducing significantly nitrite levels with a significant decrease on iNOS expression [2 (50 μM, 0.44 ± 0.03; 100 μM, 0.44 ± 0.01; p < 0.01); 3 (50 μM, 0.37 ± 0.03; 100 μM, 0.37 ± 0.01; p < 0.001); 7 (50 μM, 0.45 ± 0.06; p < 0.01)] . However, only 2 and 3 down-regulated COX-2 expression [2 (50 μM, 0.72 ± 0.04, p < 0.05; 100 μM, 0.54 ± 0.06, p < 0.01); 3 (50 μM, 0.56 ± 0.05, p < 0.05; 100 μM, 0.37 ± 0.04; p < 0.001)] and prevented IKBα degradation [2 (100 μM, 1.63 ± 0.14, p < 0.01); 3 (100 μM, 1.82 ± 0.09; p < 0.01)] ; the diacylated compounds 7 and 8 showed worse anti-inflammatory activity than the parent 3. In conclusion, 2 and 3 phenolic derivatives could play an important role in the anti-inflammatory effect of EVOO. The implication of this study for the nutrition and general health of the population rests in the possible use of natural HTy derivatives with better hydrophilic/lipophilic balance, thus improving its pharmacodynamic and pharmacokinetic profiles, as new dietary supplements in foods.