Interacción de los compuestos fenólicos del aceite de oliva virgen con las rutas de señalizacion celular / Virgin olive oil phenolic compounds interact with cellular signalling pathways

Introducción Los estudios realizados hasta la fecha, sobre los mecanismos de acción de los compuestos fenólicos, indican que sus efectos podrían deberse no sólo a la eliminación de radicales libres, sino que modularían los procesos de señalización celular o actuarían por sí mismos como moléculas señal. Métodos Se administraron 2 desayunos basados en aceite de oliva, uno de ellos con alto contenido en compuestos fenólicos (398ppm) y el otro con bajo contenido (70ppm), a 20 pacientes con síndrome metabólico, en un diseño aleatorio y cruzado. Se analizó la expresión génica postprandial en células mononucleares de sangre periférica, mediante microarrays. Resultados Hemos observado que el desayuno que incluyó un aceite rico en compuestos fenólicos reprimió la expresión de 18 genes relacionados directamente con procesos de señalización, entre ellos 12 factores de transcripción implicados en proliferación y crecimiento celular. Conclusiones Nuestros resultados sugieren que el consumo de un desayuno con aceite de oliva virgen, rico en compuestos fenólicos, reduce los procesos de proliferación celular en células mononucleares, lo que podría ser un mecanismo de protección del desarrollo de arteriosclerosis (AU)

Introduction It has been speculated that the potential beneficial effects of olive oil could be due to modulation of genes involved in proliferative, antioxidant and inflammatory pathways. Research on the acting and mechanisms of phenolic compounds indicates that the beneficial effects associated with these compounds may not only be due to the elimination of free radicals, but could also modulate cell signalling processes, or could themselves act as signaling molecules. Methods Two virgin olive oil-based breakfasts with high (398ppm) and low (70ppm) content of phenolic compounds were administered to 20 patients with metabolic syndrome following a double-blinded random crossover design. Postprandial gene expression in peripheral blood mononuclear cells was analyzed at 4hours by gene expression microarrays. Results We observed that the phenolic compounds of olive oil repressed the expression of 18 genes directly related to signalling processes, including 12 transcription factors involved in proliferation and cell growth. Conclusions Our results suggest that consumption of olive oil rich in phenolic compounds reduces the processes of cell proliferation in mononuclear cells in the postprandial state, which could reduce development of atherosclerosis (AU)

Antioxidant, antiproliferative, and pro-apoptotic capacities of pentacyclic triterpenes found in the skin of olives on MCF-7 human breast cancer cells and their effects on DNA damage.

This research aimed to investigate erythrodiol, uvaol, oleanolic acid, and maslinic acid scavenging capacities and their effects on cytotoxicity, cell proliferation, cell cycle, apoptosis, reactive oxygen species (ROS) level, and oxidative DNA damage on human MCF-7 breast cancer cell line. The results showed that erythrodiol, uvaol, and oleanolic acid have a significant cytotoxic effect and inhibit proliferation in a dose- and time-dependent manner. At 100 µM, erythrodiol growth inhibition occurred through apoptosis, with the observation of important ROS production and DNA damage, whereas uvaol and oleanolic acid growth inhibition involved cell cycle arrest. Moreover, although all tested triterpenes did not show free radical scavenging activity using ABTS and DPPH assays, they protected against oxidative DNA damage at the concentration 10 µM. Uvaol and oleanolic and maslinic acids, tested at 10 and 100 µM, also reduced intracellular ROS level and prevented H(2)O(2)-induced oxidative injury. Overall, the results suggest that tested triterpenes may have the potential to provide significant natural defense against human breast cancer.

Antioxidant and antiatherogenic activities of pentacyclic triterpenic diols and acids.

The present paper aimed to test the potential cardioprotective activity of four pentacyclic triterpenes, uvaol, erythrodiol, oleanolic acid and maslinic acid, widely distributed throughout the vegetable kingdom. For this purpose, their antioxidant and antithrombotic activities related to LDL particles have been in vitro evaluated. Results demonstrated that maslinic acid, uvaol and erythrodiol exert antiatherogenic effect while no effect was observed for oleanolic acid. Specifically, maslinic acid has shown the most potent dose-dependent antioxidant effect and did not have antithrombotic properties, whereas uvaol and erythrodiol exhibited both antioxidant and antithrombotic activities. In addition, antioxidant mechanisms of action were determined. While maslinic acid possesses dual activity acting as scavenger of free radicals and as copper chelator, uvaol is able to form a complex with copper and erythrodiol seems to behave as a retarder antioxidant. In conclusion, dietary triterpenes may exert a cardioprotective effect by different mechanisms of action related to antioxidant and antithrombotic activities.

Gene expression changes in mononuclear cells in patients with metabolic syndrome after acute intake of phenol-rich virgin olive oil.

BACKGROUND: Previous studies have shown that acute intake of high-phenol virgin olive oil reduces pro-inflammatory, pro-oxidant and pro-thrombotic markers compared with low phenols virgin olive oil, but it still remains unclear whether effects attributed to its phenolic fraction are exerted at transcriptional level in vivo. To achieve this goal, we aimed at identifying expression changes in genes which could be mediated by virgin olive oil phenol compounds in the human. RESULTS: Postprandial gene expression microarray analysis was performed on peripheral blood mononuclear cells during postprandial period. Two virgin olive oil-based breakfasts with high (398 ppm) and low (70 ppm) content of phenolic compounds were administered to 20 patients suffering from metabolic syndrome following a double-blinded, randomized, crossover design. To eliminate the potential effect that might exist in their usual dietary habits, all subjects followed a similar low-fat, carbohydrate rich diet during the study period. Microarray analysis identified 98 differentially expressed genes (79 underexpressed and 19 overexpressed) when comparing the intake of phenol-rich olive oil with low-phenol olive oil. Many of these genes seem linked to obesity, dyslipemia and type 2 diabetes mellitus. Among these, several genes seem involved in inflammatory processes mediated by transcription factor NF-kappaB, activator protein-1 transcription factor complex AP-1, cytokines, mitogen-activated protein kinases MAPKs or arachidonic acid pathways. CONCLUSION: This study shows that intake of virgin olive oil based breakfast, which is rich in phenol compounds is able to repress in vivo expression of several pro-inflammatory genes, thereby switching activity of peripheral blood mononuclear cells to a less deleterious inflammatory profile. These results provide at least a partial molecular basis for reduced risk of cardiovascular disease observed in Mediterranean countries, where virgin olive oil represents a main source of dietary fat. Admittedly, other lifestyle factors are also likely to contribute to lowered risk of cardiovascular disease in this region.

Fruit quality and olive leaf and stone addition affect Picual virgin olive oil triterpenic content.

The present research aimed to evaluate whether Picual virgin olive oil triterpenic compounds are affected by the addition of variable quantities of stones and leaves before processing or by fruit resting on the ground during 3 months. Results showed that stone addition did not influence triterpenic dialcohol content (uvaol and erythrodiol), whereas triterpenic acids (oleanolic and maslinic) increased significantly when 20 and 30% stones were added. Leaves added at 2% increased significantly oleanolic acid, maslinic acid, and erythrodiol content by 83, 41, and 36%, respectively. During fruit resting on the ground, olive oils showed no differences in uvaol content, a slight increase in erythrodiol, and a gradual increase in both oleanolic and maslinic acids, obtaining at the end of the experiment contents nearly 10- and 3-fold higher than control oils. These results confirm that olive oil triterpenic composition is modified by the factors analyzed.

Triterpenic content and chemometric analysis of virgin olive oils from forty olive cultivars.

Forty olive cultivars (Olea europaea, L.) from the World Olive Germoplasm Bank Collection of Cordoba (Spain) were studied for their oil triterpenic dialcohol (uvaol and erythrodiol) and acid (oleanolic, ursolic, maslinic) composition. Dialcohol content ranged from 8.15 to 85.05 mg/kg, erythrodiol being the most predominant (from 5.89 to 73.78 mg/kg), whereas uvaol content was found at lower levels (from 1.50 to 19.35 mg/kg). Triterpenic acid concentration oscillated between 8.90 to 112.36 mg/kg. Among them, ursolic acid was found at trace levels, while the mean values of oleanolic and maslinic acids ranged from 3.39 to 78.83 mg/kg and 3.93 to 49.81 mg/kg, respectively. The variability observed for both triterpenic dialcohols and acid content was emphasized by principal component and cluster analyses. Both analyses were able to discriminate between oil samples, especially by erythrodiol, oleanolic acid, and maslinic acids. Regarding these results, we conclude that the virgin olive oil triterpenic fraction can be considered as a useful tool to characterize monovarietal virgin olive oil.

How heating affects extra virgin olive oil quality indexes and chemical composition.

Two monovarietal extra virgin olive oils from Arbequina and Picual cultivars were subjected to heating at 180 degrees C for 36 h. Oxidation progress was monitored by measuring oil quality changes (peroxide value and conjugated dienes and trienes), fatty acid composition, and minor compound content. Tocopherols and polyphenols were the most affected by the thermal treatment and showed the highest degradation rate although their behavior was different for each cultivar. Alpha-tocopherol loss was more important in Arbequina oil whereas, total phenol content loss was greater in Picual oil. The later showed an important decrease in hydroxytyrosol (3,4-DHPEA) and its secoiridoid derivatives (3,4-DHPEA-EDA and 3,4-DHPEA-EA), while lignans decrease was lesser. For Arbequina oil these compounds remained stable, and a lowering tendency was observed for tyrosol (p-HPEA) and its derivatives (p-HPEA-EDA and p-HPEA-EA). In general, flavone content showed a decrease during heating, being higher for Arbequina oil. On the other hand, oleic acid, sterols, squalene, and triterpenic alcohols (erythrodiol and uvaol) and acids (oleanolic and maslinic) were quite constant, exhibiting a high stability against oxidation. From these results, we can conclude that despite the heating conditions, VOO maintained most of its minor compounds and, therefore, most of its nutritional properties.

Accelerated atherosclerosis in apolipoprotein E-deficient mice fed Western diets containing palm oil compared with extra virgin olive oils: a role for small, dense high-density lipoproteins.

To test the hypothesis that extra virgin olive oils from different cultivars added to Western diets might behave differently than palm oil in the development of atherosclerosis, apoE-deficient mice were fed diets containing different cultivars of olive oil for 10 weeks. Female mice were assigned randomly to one of the following five groups: (1-4) fed chow diets supplemented with 0.15% (w/w) cholesterol and 20% (w/w) extra virgin olive oil from the Arbequina, Picual, Cornicabra, or Empeltre cultivars, and (5) fed a chow diet supplemented with 0.15% cholesterol and 20% palm oil. Compared to diets containing palm oil, a Western diet supplemented with one of several varieties of extra virgin olive oil decreased atherosclerosis lesions, reduced plaque size, and decreased macrophage recruitment. Unexpectedly, total plasma paraoxonase activity, apoA-I, plasma triglycerides, and cholesterol played minor roles in the regulation of differential aortic lesion development. Extra virgin olive oil induced a cholesterol-poor, apoA-IV-enriched lipoparticle that has enhanced arylesterase and antioxidant activities, which is closely associated with reductions in atherosclerotic lesions. Given the anti-atherogenic properties of extra virgin olive oil evident in animal models fed a Western diet, clinical trials are needed to establish whether these oils are a safe and effective means of treating atherosclerosis.

Application of solid-phase microextraction to virgin olive oil quality control.

Volatiles of olive oils from 'tree-picked', 'ground-picked' and both mixed olives were analysed by solid-phase microextraction and gas chromatography with flame ionisation detection (FID). Headspace sampling was carried out for 30min of fibre exposition at 40 degrees C of sampling temperature by the selected 74 microm polydimethylsiloxane/divinylbenzene (PDMS/DVB) fibre. Chromatographic data were analysed by principal components analysis (PCA) and then selected 14 compounds from x-loading of first principal component that provides a differentiation of oils accord its sensorial characterisation. Compounds such as 4-ethylphenol and styrene were identified by gas chromatography-mass spectrometry (GC-MS) in 'ground-picked' olive oils.

Dietary cholesterol suppresses the ability of olive oil to delay the development of atherosclerotic lesions in apolipoprotein E knockout mice.

To test the hypothesis that cholesterol might suppress the beneficial effect of olive oil in atherosclerosis, we fed apoE KO mice diets containing extra virgin olive oil, either with or without cholesterol, for 10 weeks and assessed the development of atherosclerosis. Within each sex, mice were assigned randomly to one of the following four experimental groups: (1) a standard chow diet, (2) a chow diet supplemented with 0.1% cholesterol (w/w) cholesterol, (3) a chow diet enriched with 20% (w/w) extra virgin olive oil and (4) a chow diet containing 0.1% cholesterol and 20% extra virgin olive oil. On the standard chow diet, average plasma cholesterol levels were higher in males than in females. Olive oil- and cholesterol-enriched diets, separately or in combination, induced hypercholesterolemia in both sexes, and abolished the difference between the sexes in plasma cholesterol levels. The addition of cholesterol to chow or olive oil diets decreased apolipoprotein A-I significantly in females and serum paraoxonase activities in males. The latter activity was higher in females than in males. In both sexes, the size of aortic atherosclerotic lesions was similar in olive oil- and chow-fed animals and smaller than in cholesterol-supplemented groups. Size of aortic lesions were positively correlated with circulating paraoxonase activity, particularly in males, and the relationship remained after adjusting for apolipoprotein A-I and HDL cholesterol levels. Our results demonstrate that the nutritional regulation of paraoxonase is an important determinant of atherosclerotic lesions dependent on sex. They also suggest that the mere inclusion of olive oil in Western diets is insufficient and the adoption of Mediterranean diet would be more effective in retarding the development of atherosclerotic lesions.