title: Effect of olive oil phenols on the production of inflammatory mediators in freshly isolated human monocytes.
abstract: Recent in vitro and in vivo studies suggest that the anti-inflammatory properties of extra virgin olive oil may be involved in the prevention of chronic degenerative diseases. In this study, the ability of olive oil phenols to influence the release of superoxide anions (O2-), prostaglandin E2 (PGE2) and tumor necrosis factor α (TNFα) and the expression of cyclooxygenase2 (COX2) in human monocytes, freshly isolated from healthy donors, was investigated. O2- were measured by superoxide dismutase-inhibitable cytochrome c reduction and PGE2 and TNFα production were determined in culture medium with appropriate enzyme immunoassay kits. COX2 mRNA and protein were evaluated by quantitative reverse transcription-polymerase chain reaction and Western immunoblotting, respectively. Treatment of monocytes for 24 h with 100 μM of hydroxytyrosol (3,4-DHPEA), tyrosol (p-HPEA) and their secoiridoid derivatives (3,4-DHPEA and p-HPEA linked to the dialdehydic form of elenolic acid: 3,4-DHPEA-EDA and p-HPEA-EDA, respectively) significantly (P<.05) inhibited the production of O2(-) as follows: 3,4-DHPEA (40%,), p-HPEA (9%), 3,4-DHPEA-EDA (25%) and p-HPEA-EDA (36%). Hydroxytyrosol also considerably reduced the expression of COX2 at both the mRNA and protein level (P<.05) and caused a clear dose-dependent reduction of PGE2 released into the culture medium (45% and 71% at 50 and 100 μM, respectively, P<.05). The COX2 mRNA was also efficiently inhibited by the secoiridoids. Moreover, it was shown that hydroxytyrosol increased the monocytes TNFα production. In addition to other chemopreventive properties, these results suggest that the health effects of olive oil phenols may be related to their ability to modulate the production of pro-inflammatory molecules, a property common to non-steroidal anti-inflammatory drugs.
authors.affiliation: Dipartimento di Specialità Medico-Chirurgiche e Sanità Pubblica, Sezione di Epidemiologia Molecolare ed Igiene Ambientale, Università degli Studi di Perugia, Perugia, Italy. patriros@unipg.it
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rosignoli
authors.forename: Raffaela
authors.initials: R
authors.lastname: Fuccelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Fabiani
authors.forename: Maurizio
authors.initials: M
authors.lastname: Servili
authors.forename: Guido
authors.initials: G
authors.lastname: Morozzi
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002470:Cell Survival; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D000069463:Olive Oil; D010636:Phenols / Q000494:pharmacology*; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives / Q000494:pharmacology; D010938:Plant Oils / Q000737:chemistry* / Q000494:pharmacology*; D011714:Pyrans / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000069463:Olive Oil; D010636:Phenols; D010938:Plant Oils; D011714:Pyrans; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C005975:3,4-dihydroxyphenylethanol; D013481:Superoxides; C011867:4-hydroxyphenylethanol; C000352:elenolic acid; C016658:phorbolol myristate acetate; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone; D010626:Phenylethyl Alcohol; D013755:Tetradecanoylphorbol Acetate
keywords: 3,4-DHPEA; 3,4-DHPEA-EDA; CAT; COX2; H7; Human monocytes; Hydroxytyrosol; PGE2; PMA; ROS; Superoxide anion; TNFα; catalase; cyclooxygenase2; dialdehydic form of elenolic acid linked to hydroxytyrosol; dialdehydic form of elenolic acid linked to tyrosol or oleocanthal; hydroxystaurosporine; hydroxytyrosol; p-HPEA; p-HPEA-EDA; phorbol 12-myristate 13-acetate; prostaglandin E2; reactive oxygen species; tyrosol