1,720,978 research outputs found
Effect of olive oil phenols on the production of inflammatory mediators in freshly isolated human monocytes.
No full textRecent 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 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 qPCR 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<0.05) inhibited the production of O2.- as follow: 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<0.05), and caused a clear dose-dependent reduction of PGE2 released into the culture medium (45% and 71% at 50 and 100 μM, respectively, P<0.05). 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-steroideal anti-inflammatory drugs (NSAIDs)
Effetti anti-infiammatori dell’idrossitirosolo, principale fenolo presente nell’olio d’oliva, in vivo sul modello animale
No full textIl consumo di olio extravergine d’oliva, principale fonte di grassi nella Dieta Mediterranea, è associato ad un ridotto rischio di contrarre alcune patologie cronico-degenerative, in particolare i tumori e le malattie cardio-vascolari. Tali patologie riconoscono sia alcuni fattori di rischio che alcune condizioni di rischio comuni. Tra queste il processo infiammatorio cronico sembra essere di particolare importanza. Dati recenti hanno indicato che alcuni composti fenolici presenti nell’olio d’oliva, in particolare l’idrossitirosolo (HT), hanno potenti attività anti-infiammatorie “in vitro”. D’altro canto poco si conosce riguardo il potenziale anti-infiammatorio di questo composto “in vivo”. In questo lavoro riportiamo i risultati di nostre recenti ricerche che dimostrano come l’HT sia in grado di influenzare il processo infiammatorio in topi trattati con il Lipopolisaccaride (LPS).
- Gli animali, suddivisi in 5 gruppi, sono stati trattati come segue: 1) controllo, nessun trattamento; 2) LPS, trattamento con solo LPS (50μg/topo); 3) pre-trattamento con HT (40 mg/kg p.c.) iniziato 18 ore prima del trattamento con LPS (2 somministrazioni); 4) pre-trattamento con HT (80 mg/kg p.c.) iniziato 18 ore prima del trattamento con LPS (2 somministrazioni); 5) pre-trattamento con HT (80 mg/kg p.c.) iniziato 72 ore prima del trattamento con LPS (4 somministrazioni). Due ore dopo il trattamento con LPS gli animali sono stati sacrificati, è stato prelevato il sangue e sono stati valutati i seguenti parametri: nei leucociti il danno al DNA (Comet assay) e l’espressione della COX-2 (qPCR), nel plasma il potere antiossidante (FRAP) e la concentrazione di TNF-a (ELISA).
-Il trattamento con LPS ha causato un significativo aumento (50%) del danno al DNA che veniva ridotto dall’HT in maniera dose e tempo dipendente. Il pre-trattamento con HT per 72 ore riduceva il danno al DNA a valori addirittura inferiori rispetto al valore ottenuto senza trattamento con LPS. Risultati essenzialmente simili sono stati ottenuti anche per quanto riguarda l’espressione, a livello di mRNA, della COX-2 e la concentrazione di TNF-a. L’incremento dell’espressione della COX-2 indotto dall’LPS veniva significativamente ridotto dall’HT in tutti i gruppi di trattamento con piccole differenze correlate alla dose e al tempo di pre-trattamento, in particolare è stata osservata una riduzione del 55% con HT 40mg/kg p.c., del 62 % con HT 80mg/kg p.c., e del 77% con HT 80mg/kg p.c. per 72 ore. Analogo andamento è stato osservato nei riguardi della produzione del TNF-a, anche in questo caso il pre-trattamento con HT per 72 ore alla dose più alta (80 mg/kg p.c.) ha dato la maggiore inibizione (60%). Un andamento opposto si è evidenziato per quanto riguarda il potere anti-ossidante del plasma che è risultato minimo sia nel gruppo di controllo che in quello trattato con il solo LPS, ed aumentato da tutti i trattamenti con HT .
Questi dati, nel loro insieme, indicano che l’HT è in grado di esplicare importati attività anti-infiammatorie, in vivo, agendo a vari livelli: incrementando le capacità antiossidanti del plasma e modulando sia la produzione del TNF-a che l’espressione della COX-2. Si sottolinea l’importanza di effettuare ulteriori approfondimenti attraverso studi di intervento sull’uomo
In vitro chemo-preventive activities of hydroxytyrosol: the main phenolic compound present in extra-virgin olive oil.
No full textThe co-incubation in the culture medium with hydroxytyrosol [3,4-dihydroxyphenyl ethanol (3,4-DHPEA)], the main phenolic compound present in extra-virgin olive oil, and H2O2 reduces the oxidative DNA damage in peripheral blood mononuclear cells (PBMC). In this study we investigate, by the comet assay, the ability of 3,4-DHPEA to inhibit the H2O2 induced DNA damage when pre-incubated with PBMC and then removed before the exposure of cells to H2O2. Low doses of 3,4-DHPEA (10–100 μM) pre-incubated for 30 min with PBMC reduced the DNA damage induced by the treatment with H2O2 200 μM for 5 min at 4 °C. Prolonging the exposure time up to 6 h completely prevented the DNA damage. Furthermore we extensively analysed, by the MTT assay, the anti-proliferative activities of 3,4-DHPEA on breast (MDA and MCF-7), prostate (LNCap and PC3) and colon (SW480 and HCT116) cancer cell lines and correlated these effects with the H2O2 accumulation. The concentration of H2O2 in the culture medium was measured by the ferrous ion oxidation–xylenol orange method. The proliferation of all the cell lines was inhibited but at different levels: the prostate cancer cells were more resistant to the growth inhibition with respect to breast and colon cancer cells. The ability of the different cell lines to remove H2O2 from the culture medium was inversely correlated with their sensitivity to the anti-proliferative effect of 3,4-DHPEA. Therefore, 3,4-DHPEA may act as a chemopreventive agent acting on both initiation and promotion/progression phases of carcinogenesis
Preventive activity of antioxidants on lymphocytes DNA damage induced by PMA-stimulated monocytes.
No full textChemopreventive activities of hydroxytyrosol: the major phenol alcohol of extra-virgin olive oil
No full textABSTRACT
The beneficial role of extra-virgin olive oil on human health was recently attributed to the presence of minor components, with a particular interest toward the phenolic compounds. The phenolic composition of olive oil is complex and includes hydroxytyrosol (3,4-dihydroxyphenylethanol: HT), tyrosol (hydroxyphenylethanol), the dialdehydic form of elenolic acid linked to hydroxytyrosol or tyrosol (oleocanthal), oleuropein aglycon and lignans. Olive oil phenols, in particular HT, have been deeply investigated in the last past years and it has been showed that this phenol may be involved in the prevention of chronic-degenerative disease, like cardiovascular diseases and cancer, through antioxidant mechanisms. However, the biological effects of olive oil polyphenols are not limited to the antioxidant property. Indeed, several researchers have recently demonstrated that olive oil polyphenols are also able to modulate both gene expression and different pathways involved in the regulation of many physiological and pathological conditions. In this field, we show our recent findings on the in vitro chemopreventive activities of HT. We have demonstrated that HT, at relatively high doses (100μM), is able to inhibit proliferation and to arrest cell cycle progression through the up-regulation of the cyclin dependent protein kinase inhibitors p21 and p27 on HL60 promyelocytic cell line. These effects were associated to the induction of differentiation and apoptosis. The initial stress signal responsible for these effects was the HT-induced extracellular production of H2O2. HT was also able to inhibit the proliferation of human tumour cells derived from colon, prostate and breast, indicating an important role in the prevention of the promotion phase of carcinogenesis. In addition, we have observed by the comet assay that HT, at lower doses (1-10μM), is able to inhibit the oxidative DNA damage in human leukocytes so suggesting a preventive mechanism in the initiation phase of carcinogenesis. These results have allowed us to highlight that HT is able to induce either pro-oxidant or anti-oxidant effects which are depend on exposition doses. Furthermore, we demonstrated that HT (50-100μM) was able to prevent LPS-mediated COX2 induction on human monocytes at both mRNA and protein levels. These effects were associated to a significant reduction of PGE2 accumulation in the culture medium. In addition, in the same experimental conditions HT incremented the release of TNFα by monocytes. All together, our in vitro data give further support to the hypothesis that olive oil phenols may play a role in the cancer prevention properties of the Mediterranean diet
The hydroxytyrosol-dependent increase of TNF-α in LPS-activated human monocytes is mediated by PGE2 and adenylate cyclase activation
No full textAn accurate regulation of PGE2 and TNF-a production is an important event for a physiological inflammation
process. We have recently reported that in LPS-activated human monocytes hydroxytyrosol,
the main phenol present in extra virgin olive oil reduced both the COX-2 gene expression and PGE2 secretion
while it increased the TNF-a accumulation in the culture medium. Here we have investigated
whether these effects were related to each other, clarifying the possible mechanisms involved. We found
that hydroxytyrosol (100 lM) increased the TNF-a mRNA level in LPS-activated human monocytes as
evaluated by both RT-PCR and real time PCR (qPCR). Exogenous PGE2 reduced both TNF-a mRNA and
TNF-a secretion (EIA assay) while the activation of adenylate cyclase by forskolin decreased only the
TNF-a secretion but did not influence the TNF-a mRNA level. Acting similarly to non steroidal antiinflammatory
drugs (NSAIDs), the hydroxytyrosol could be used to develop innovative drugs for the control
of inflammation and immune response. The decrease of TNF mediated by forskolin, moreover, could
suggest that the pharmacological regulation of cAMP production may represent a strategy to control the
side effects of NSAIDs
Mutagenicità e genotossicità di hamburger cotti alla piastra ed effetto preventivo dei fenoli dell’olio d’oliva.
No full textINTRODUZIONE
La carne ha un ruolo importante nell’alimentazione umana in quanto rappresenta una fonte di proteine ad elevato valore biologico, ferro biodisponibile e vitamine del gruppo B (1). Tuttavia, sulla base di numerosi studi epidemiologici osservazionali, di meta-analisi e sperimentazioni in vivo, lo IARC (Agenzia Internazionale per la Ricerca sul Cancro) ha classificato la carne processata nel gruppo 1 (cancerogeno certo) e la carne rossa nel gruppo 2A (cancerogeno probabile) (2). Tra i meccanismi molecolari alla base dell’effetto pro-cancerogeno della carne, un ruolo importante è stato attribuito alla formazione di composti mutageni e cancerogeni, tra cui IPA e ammine eterocicliche aromatiche, durante la cottura ad alte temperature come, ad esempio, alla piastra, alla griglia, alla brace (3). In questo studio si è voluta investigare l’attività genotossica e mutagena di estratti ottenuti da hamburger di carne bovina cotti alla piastra in diverse condizioni. Sulla base delle numerose evidenze degli effetti anti-cancerogeni dei fenoli dell’olio di oliva (4-6) si è investigata inoltre l’eventuale riduzione delle suddette attività in presenza di una miscela fenolica ottenuta da olio extravergine di oliva.
MATERIALI E METODI
Gli estratti, dopo omogenizzazione in HCl e centrifugazione, sono stati preparati attraverso estrazione solido-liquido con Amberlite XAD-2 ed acetone secondo il metodo di Bjeldanes et al. che assicura un efficiente recupero di sostanze mutagene (7). L’attività genotossica è stata valutata come rotture al DNA tramite il comet assay su cellule mononucleate isolate da sangue periferico (PBMC). L’attività mutagena è stata valutata tramite test di Ames. Entrambe i test sono stati eseguiti in presenza/assenza della frazione microsomiale S9.
RISULTATI
L’estratto della carne cotta ad alte temperature è risultato altamente mutageno e ha indotto un notevole danno al DNA nelle cellule target. L’attivazione metabolica (S9), necessaria per osservare l’effetto mutageno, non si è invece rivelata necessaria per ottenere le rotture al DNA. La presenza della miscela fenolica, nonostante le basse dosi utilizzate, ha ridotto in maniera statisticamente significativa sia l’attività genotossica che mutagena dell’estratto, riportando quest’ultima a valori prossimi al controllo.
CONCLUSIONI
La cottura della carne alla piastra, protratta a lungo e ad alte temperature, favorisce la formazione di sostanze genotossiche e mutagene. La riduzione di queste attività, ottenuta con la miscela fenolica da olio d’oliva, suggerisce che una maggiore attenzione nei metodi di cottura ed il concomitante consumo di una dieta ricca di fenoli antiossidanti, potrebbero contribuire a ridurre il rischio cancerogeno associato al consumo di carne
Apple intake and cancer risk: a systematic review and meta-analysis of observational studies
No full textObjective: Conflicting results on the association between fruit consumption and
cancer risk have been reported. Little is known about the cancer preventive effects
of different fruit types. The present meta-analysis investigates whether an
association exists between apple intake and cancer risk.
Design: Relevant observational studies were identified by literature search
(PubMed, Web of Science and Embase). A random-effect model was used to
estimate the cancer risk in different anatomical sites. Between-study heterogeneity
and publication bias were assessed using adequate statistical tests.
Results: Twenty case–control (three on lung, five on colorectal, five on breast, two
on oesophageal, three on oral cavity, two on prostate and one each on pancreas,
bladder, larynx, ovary, kidney and brain cancer) and twenty-one cohort (seven on
lung, two on colorectal, three on breast and one each on oesophageal, pancreas,
bladder, kidney, endometrial, head–neck, urothelial and stomach cancer) studies
met the inclusion criteria. Comparing the highest v. lowest level of apple
consumption, the reduction of lung cancer risk was statistically highly significant
in both case–control (OR =0·75; 95% CI 0·63, 0·88; P =0·001, I 2=0%) and cohort
studies (relative risk=0·89; 95% CI 0·84, 0·94; P<0·001, I 2 =53 %). Instead, in the
case of colorectal (OR=0·66; 95% CI 0·54, 0·81; P<0·001, I 2=55 %), breast
(OR=0·79; 95% CI 0·73, 0·87; P<0·001, I 2=1%) and overall digestive tract
(OR=0·50; 95% CI 0·36, 0·69; P <0·001, I 2=90 %) cancers a significant preventive
effect of apples was found only in case–control studies while prospective studies
indicated no effect. No evidence of publication bias could be detected for
colorectal, oral cavity, oesophageal and breast cancer. However, some
confounding effects may be present and related to the consumption of other
fruit which have not been considered as adjusting factors.
Conclusions: The present meta-analysis indicates that consumption of apples is
associated with a reduced risk of cancer in different anatomical sites
Health Outcomes Associated with Olive Oil Intake: An Umbrella Review of Meta-Analyses
No full textSeveral studies suggested a negative association between olive oil (OO) consumption and the risk of several chronic diseases. However, an attempt to systematically search, organize, and evaluate the existing evidence on all health outcomes associated with OO consumption is lacking. The objective of this review is to describe the multiple health outcomes associated with OO consumption. The Medline, Scopus, and Web of Science databases were searched through 5 April 2024. The selected studies met all of the following criteria: (1) a meta-analysis of both observational (case–control and cohort studies) and interventional studies (trials), (2) an evaluation of the association between OO consumption, mortality, and/or the incidence of non-communicable/chronic degenerative diseases, and (3) a study population ≥18 years old. Two independent reviewers extracted the relevant data and assessed the risk of bias of individual studies. The PRISMA statement and guidelines for the Integration of Evidence from Multiple Meta-Analyses were followed. The literature search identified 723 articles. After selection, 31 articles were included in this umbrella review. The primary health benefits of OO were observed in cardiovascular diseases and risk factors, cancer, mortality, diabetes, and specific biomarkers related to anthropometric status and inflammation. As a key component of the Mediterranean diet, OO can be considered a healthy dietary choice for improving positive health outcomes
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