title: Naturally occurring hydroxytyrosol derivatives: hydroxytyrosyl acetate and 3,4-dihydroxyphenylglycol modulate inflammatory response in murine peritoneal macrophages. Potential utility as new dietary supplements.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Seville , Profesor García González Street 2, 41012 Seville, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Aparicio-Soto
authors.forename: Susana
authors.initials: S
authors.lastname: Sánchez-Fidalgo
authors.forename: Alejandro
authors.initials: A
authors.lastname: González-Benjumea
authors.forename: Inés
authors.initials: I
authors.lastname: Maya
authors.forename: José G
authors.initials: JG
authors.lastname: Fernández-Bolaños
authors.forename: Catalina
authors.initials: C
authors.lastname: Alarcón-de-la-Lastra
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000032:analysis; D004789:Enzyme Activation / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D009573:Nitrites / Q000378:metabolism; D000069463:Olive Oil / Q000737:chemistry*
chemical_list: D000085:Acetates; D000893:Anti-Inflammatory Agents; D002396:Catechols; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; C000606205:Nfkbia protein, mouse; D009573:Nitrites; D000069463:Olive Oil; C524604:hydroxytyrosyl acetate; D000072000:NF-KappaB Inhibitor alpha; D008734:Methoxyhydroxyphenylglycol; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D020928:Mitogen-Activated Protein Kinases; C010117:3,4-dihydroxyphenylglycol
keywords: EVOO; NF-κB; inflammation; macrophages; phenols