scholarly journals Extra Virgin Olive Oil Phenol Extracts Exert Hypocholesterolemic Effects through the Modulation of the LDLR Pathway: In Vitro and Cellular Mechanism of Action Elucidation

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1723 ◽  
Author(s):  
Carmen Lammi ◽  
Maria Bellumori ◽  
Lorenzo Cecchi ◽  
Martina Bartolomei ◽  
Carlotta Bollati ◽  
...  

This study was aimed at investigating the hypocholesterolemic effects of extra virgin olive oil (EVOO) phenols and the mechanisms behind the effect. Two phenolic extracts were prepared from EVOO of different cultivars and analyzed using the International Olive Council (IOC) official method for total phenols, a recently validated hydrolytic procedure for total hydroxytyrosol and tyrosol, and 1H-NMR analysis in order to assess their secoiridoid profiles. Both of the extracts inhibited in vitro the 3-hydroxy-3-methylglutaryl co-enzyme A reductase (HMGCoAR) activity in a dose-dependent manner. After the treatment of human hepatic HepG2 cells (25 µg/mL), they increased the low-density lipoprotein (LDL) receptor protein levels through the activation of the sterol regulatory element binding proteins (SREBP)-2 transcription factor, leading to a better ability of HepG2 cells to uptake extracellular LDL molecules with a final hypocholesterolemic effect. Moreover, both of the extracts regulated the intracellular HMGCoAR activity through the increase of its phosphorylation by the activation of AMP-activated protein kinase (AMPK)-pathways. Unlike pravastatin, they did not produce any unfavorable effect on proprotein convertase subtilisin/kexin 9 (PCSK9) protein level. Finally, the fact that extracts with different secoiridoid profiles induce practically the same biological effects suggests that the hydroxytyrosol and tyrosol derivatives may have similar roles in hypocholesterolemic activity.

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 314 ◽  
Author(s):  
Abu Bakar Siddique ◽  
Judy Ann King ◽  
Sharon A. Meyer ◽  
Khaldoun Abdelwahed ◽  
Belnaser Busnena ◽  
...  

Epidemiological and clinical studies compellingly showed the ability of Mediterranean diet rich in extra-virgin olive oil (EVOO) to reduce multiple diseases such as cancer, cardiovascular diseases, and aging cognitive functions decline. The S-(−)-Oleocanthal (OC) is a minor phenolic secoiridoid exclusively found in extra-virgin olive oil (EVOO). OC recently gained notable research attention due to its excellent in vitro and in vivo biological effects against multiple cancers, inflammations, and Alzheimer’s disease. However, OC safety has not been comprehensively studied yet. This study reports for the first time the detailed safety of oral single OC dose in Swiss albino mice, applying the OECD 420 procedure. Male and female Swiss albino mice (n = 10) were orally treated with a single OC dose of either 10, 250, or 500 mg/kg bodyweight or equivalent volumes of distilled water. Mice fed a regular diet, and carefully observed for 14 days. Further, mice were then sacrificed, blood samples, and organs were collected and subjected to hematological, biochemical, and histological examinations. OC 10 mg/kg oral dose appears to be without adverse effects. Further, 250 mg/kg OC, p.o., is suggested as a possible upper dose for preclinical studies in the future.


2011 ◽  
Vol 106 (1) ◽  
pp. 33-36 ◽  
Author(s):  
Giuliana Trefiletti ◽  
Anna Rita Togna ◽  
Valentina Latina ◽  
Carolina Marra ◽  
Marcella Guiso ◽  
...  

Extra-virgin olive oil is an integral ingredient of the Mediterranean diet, and it has been suggested that its high consumption has beneficial effects on human health. Its protective effect, in particular against the development of CVD, has been related not only to the high content of oleic acid, but also to the antioxidant and anti-inflammatory properties of polyphenols. In order to verify the anti-inflammatory and anti-atherogenic properties of hydroxy-isochromans, a class of ortho-diphenols present in extra-virgin olive oil, we investigated the potential ability of 1-phenyl-6,7-dihydroxy-isochroman (L137) to modulate the production of key inflammatory mediators by human monocytes, by evaluating its in vitro effects on prostanoid (thromboxane A2 and PGE2) and cytokine (TNF-α) production. Its effect on the protein expression of the inducible form of cyclo-oxygenase-2 (COX-2), a pro-inflammatory enzyme responsible for elevated prostanoid levels, was also explored. The results showed that L137 significantly inhibited both prostanoid and TNF-α production in lipopolysaccharide-primed human monocytes in a dose-dependent manner, by inhibiting the COX activity of COX-2. We also demonstrated that the effects of the isochroman are mediated, at least partly, through the suppression of NF-κB activation leading to the down-regulation of the synthesis of COX-2.


Nutrients ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 969 ◽  
Author(s):  
Lorena Martínez ◽  
Gaspar Ros ◽  
Gema Nieto

There is a high demand for functional meat products due to increasing concern about food and health. In this work, Zn and Se bioavailability was increased in chicken meat emulsions that are enriched with Hydroxytyrosol (HXT), a phenolic compound obtained from olive leaf. Six different chicken emulsions were elaborated. Three were made with broiler chicken meat supplemented with inorganic Zn and Se: control, one with HXT (50 ppm) added and one with HXT (50 ppm) and Extra Virgin Olive Oil (EVOO) (9.5%) added; and, three were made with chicken meat from chickens fed a diet that was supplemented with organic Zn and Se: control, one with HXT (50 ppm) added and one with HXT (50 ppm) and EVOO (9.5%) added. The samples were digested in vitro and the percent decomposition of phenolic compounds was measured by HPLC. Mineral availability (Fe, Zn and Se) was measured by cell culture of the Caco-2 cell line and the results were compared with mineral standards (Fe, Zn, and Se). The data obtained showed that neither HXT resistance to digestion nor Fe availability was affected by the presence of organic Zn and Se or phenolic compounds. Zn uptake increased in the presence of HXT, but not when its organic form was used, while Se uptake increased but it was not affected by the presence of HXT. It was concluded that the enrichment of meat—endogenously with organic minerals and exogenously with phenolic compounds—could be considered an interesting strategy for future research and applications in the current meat industry.


Antioxidants ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 170 ◽  
Author(s):  
Gabriele Serreli ◽  
Monica Deiana

Extra virgin olive oil (EVOO) polyphenols beneficial effects have widely been debated throughout the last three decades, with greater attention to hydroxytyrosol and tyrosol, which are by far the most studied. The main concern about the evaluation of EVOO phenols activities in vitro and in vivo is that the absorption and metabolism of these compounds once ingested lead to the production of different metabolites in the human body. EVOO phenols in the ingested forms are less concentrated in human tissues than their glucuronide, sulfate and methyl metabolites; on the other hand, metabolites may undergo deconjugation before entering the cells and thus act as free forms or may be reformed inside the cells so acting as conjugated forms. In most in vitro studies the presence of methyl/sulfate/glucuronide functional groups does not seem to inhibit biological activity. Parent compounds and metabolites have been shown to reach tissue concentrations useful to exert beneficial effects others than antioxidant and scavenging properties, by modulating intracellular signaling and improving cellular response to oxidative stress and pro-inflammatory stimuli. This review aims to give an overview on the reported evidence of the positive effects exerted by the main EVOO polyphenols metabolites in comparison with the parent compounds.


Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2179 ◽  
Author(s):  
Maria Bellumori ◽  
Lorenzo Cecchi ◽  
Marzia Innocenti ◽  
Maria Lisa Clodoveo ◽  
Filomena Corbo ◽  
...  

The health claims of olive oil represent an important marketing lever in raising the willingness to pay for a product, but world producers of extra virgin olive oil (EVOO) do not take advantage of it because there are still obstacles to their use. Among these, one issue is the lack of an official method for determination of all free and linked forms derived from secoiridoidic structures of hydroxytyrosol and tyrosol. In this study, different acidic hydrolytic procedures for analyzing the linked forms were tested. The best method was validated and then applied to more than 100 EVOOs. The content of oleuropein and ligstroside derivatives in EVOOs was indirectly evaluated comparing the amount of phenols before and after hydrolysis. After acidic hydrolysis, a high content of total tyrosol was found in most of the EVOOs. The use of a suitable corrective factor for the evaluation of hydroxytyrosol allows an accurate determination only using pure tyrosol as a standard. Further knowledge on the concentration of total hydroxytyrosol will assist in forecasting the resistance of oils against aging, its antioxidant potential and to better control its quality over time.


2021 ◽  
Vol 8 ◽  
Author(s):  
Daniela Gabbia ◽  
Sara Carpi ◽  
Samantha Sarcognato ◽  
Luana Cannella ◽  
Martina Colognesi ◽  
...  

Liver fibrosis, which is the outcome of wound-healing response to chronic liver damage, represents an unmet clinical need. This study evaluated the anti-fibrotic and anti-inflammatory effects of the polyphenol oleocanthal (OC) extracted from extra virgin olive oil (EVOO) by an in vitro/in vivo approach. The hepatic cell lines LX2 and HepG2 were used as in vitro models. The mRNA expression of pro-fibrogenic markers, namely alpha-smooth muscle actin (α-SMA), collagen type I alpha 1 chain (COL1A1), a panel of metalloproteinases (MMP1, MMP2, MMP3, MMP7, MMP9) and vascular endothelial growth factor A (VEGFA) as well as the pro-oxidant genes NADPH oxidases (NOXs) 1 and 4 were evaluated in TGF-β activated LX2 cells by qRT-PCR. α-SMA and COL1A1 protein expression was assessed by immunofluorescence coupled to confocal microscopy. VEGFA release from LX2 was measured by ELISA. We also evaluated the amount of reactive oxygen species (ROS) produced by H2O2 activated- HepG2 cells. In vivo, OC was administered daily by oral gavage to Balb/C mice with CCl4-induced liver fibrosis. In this model, we measured the mRNA hepatic expression of the three pro-inflammatory interleukins (IL) IL6, IL17, IL23, chemokines such as C-C Motif Chemokine Ligand 2 (CCL2) and C-X-C Motif Chemokine Ligand 12 (CXCL12), and selected miRNAs (miR-181-5p, miR-221-3p, miR-29b-3p and miR-101b-3p) by qRT-PCR. We demonstrated that OC significantly downregulated the gene/protein expression of α-SMA, COL1A1, MMP2, MMP3, MMP7 and VEGF as well as the oxidative enzymes NOX1 and 4 in TGFβ1-activated LX2 cells, and reduced the production of ROS by HepG2. In vivo OC, beside causing a significant reduction of fibrosis at histological assessment, counteracted the CCl4-induced upregulation of pro-fibrotic and inflammatory genes. Moreover, OC upregulated the anti-fibrotic miRNAs (miR-29b-3p and miR-101b-3p) reduced in fibrotic mice, while downregulated the pro-fibrotic miRNAs (miR-221-3p and miR-181-5p), which were dramatically upregulated in fibrotic mice. In conclusion, OC exerts a promising antifibrotic effect via a combined reduction of oxidative stress and inflammation involving putative miRNAs, which in turn reduces hepatic stellate cells activation and liver fibrosis.


Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 685 ◽  
Author(s):  
Paloma Rodríguez-López ◽  
Jesús Lozano-Sanchez ◽  
Isabel Borrás-Linares ◽  
Tatiana Emanuelli ◽  
Javier A. Menéndez ◽  
...  

Extra-virgin olive oil is regarded as functional food since epidemiological studies and multidisciplinary research have reported convincing evidence that its intake affects beneficially one or more target functions in the body, improves health, and reduces the risk of disease. Its health properties have been related to the major and minor fractions of extra-virgin olive oil. Among olive oil chemical composition, the phenolic fraction has received considerable attention due to its bioactivity in different chronic diseases. The bioactivity of the phenolic compounds could be related to different properties such as antioxidant and anti-inflammatory, although the molecular mechanism of these compounds in relation to many diseases could have different cellular targets. The aim of this review is focused on the extra-virgin olive oil phenolic fraction with particular emphasis on (a) biosynthesis, chemical structure, and influence factors on the final extra-virgin olive oil phenolic composition; (b) structure–antioxidant activity relationships and other molecular mechanisms in relation to many diseases; (c) bioavailability and controlled delivery strategies; (d) alternative sources of olive biophenols. To achieve this goal, a comprehensive review was developed, with particular emphasis on in vitro and in vivo assays as well as clinical trials. This report provides an overview of extra-virgin olive oil phenolic compounds as a tool for functional food, nutraceutical, and pharmaceutical applications.


2016 ◽  
Vol 9 (11) ◽  
Author(s):  
Najmeh Sadat Boland-Nazar ◽  
Zahra Eslamirad ◽  
Hossein Sarmadian ◽  
Reza Ghasemikhah

Antioxidants ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 217 ◽  
Author(s):  
Thays Helena Borges ◽  
Adriana Serna ◽  
Luis Carlos López ◽  
Luis Lara ◽  
Rosa Nieto ◽  
...  

The health benefits of extra virgin olive oil (EVOO) are related to its chemical composition and the presence of bioactive compounds with antioxidant properties. The aim of this study was to evaluate antioxidant compounds (pigments, coenzyme Q10 (CoQ10) and phenolic compounds) and antioxidant properties of EVOO from the same region comparing different cultivars (Hojiblanca and Arbequina), harvest year and crop stage. Antioxidant properties of oils were studied before and after a gastrointestinal digestion process, by in vitro assays (DPPH, ABTS and FRAP) and antioxidant markers in Caco-2 cells (reactive oxygen species production). The content of bioactive compounds measured was significantly affected by cultivar and harvest year (except for carotenoids) and by the crop stage (except for coenzyme Q10). Higher amounts of coenzyme Q10 were observed in Hojiblanca than in Arbequina EVOO. Total phenol content and antioxidant properties were also different depending on cultivar and harvest year and the in vitro digestion process strongly improved antioxidant marker values. Antioxidant potential in bioaccessible fractions was mainly related to the content of coenzyme Q10 and phenolic compounds in EVOO. Chemometric analysis showed that the oils were clearly classified by cultivars, harvest and crop stage, according to the chemical composition and antioxidant activity analyzed in the present study.


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