Farré, L., Casanova, I., Guerrero, S., Trias, M., Capellá, G., and Mangues, R. (). Heterotopic implantation alters the regulation of apoptosis and the. psychological mode/s of romance and charisma, in: SOCIAL SCIENCE. INFORMATION 23 CASANOVA, Memórias, vol.S, p 24 CASANOVA, Memórias, vol.7, p
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Polyphenols and omega-3 as nutriceuticals | Encyclopedia MDPI
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The adequate combination of the well-recognized individual nutraceutical properties of polyphenols and omega-3 polyunsaturated fatty acids from fish oils eicosapentaenoic and docosahexaenoic acids , particularlly their single antioxidant and anti-inflammatory properties, may offer a powerful tool for the design of successfully nutritional interventions for the prevention and palliation of a plethora of human diseases, often diet-related, whose etiology and progression are characterized by redox homeostasis disturbances and a low-grade of chronic inflammation. However, the certain mechanisms behind their biological activities, in vivo interaction both between them and other food compounds , and their optimal doses and consumption are not well-known yet. Therefore, we review here the recent accumulated evidence in both preclinical and clinical trials, of the cooperative action between polyphenols and fish oils as nutraceuticals on human health, focusing on the mechanisms and pathways described and the effects reported. The final objective is to provide useful information for developing effective strategies of personalized nutrition based on the combined used of these bioactive food compounds. MetS is considered a risk factor for noncommunicable diseases such as type 2 diabetes and cardiovascular diseases CVD [ 4 ].
The adequate combination of the well-recognized individual nutraceutical properties of polyphenols and omega-3 polyunsaturated fatty acids from fish oils eicosapentaenoic and docosahexaenoic acids , particularlly their single antioxidant and anti-inflammatory properties, may offer a powerful tool for the design of successfully nutritional interventions for the prevention and palliation of a plethora of human diseases, often diet-related, whose etiology and progression are characterized by redox homeostasis disturbances and a low-grade of chronic inflammation.
However, the certain mechanisms behind their biological activities, in vivo interaction both between them and other food compounds , and their optimal doses and consumption are not well-known yet.
Therefore, we review here the recent accumulated evidence in both preclinical and clinical trials, of the cooperative action between polyphenols and fish oils as nutraceuticals on human health, focusing on the mechanisms and pathways described and the effects reported.
The final objective is to provide useful information for developing effective strategies of personalized nutrition based on the combined used of these bioactive food compounds. MetS is considered a risk factor for noncommunicable diseases such as type 2 diabetes and cardiovascular diseases CVD [ 4 ]. Other main chronic illnesses promoted by obesity are cancer and neurodegenerative pathologies [ 5 ].
Interestingly, all these pathologies are characterized by an increase in oxidative stress and a proinflammatory status [ 6 ].
Among those, dietary polyphenols are often considered because they are one of the most important groups of natural antioxidants and anti-inflammatory agents found in human diets, including fruits, vegetables, grains, tea, essential oils, and their derived foods and beverages [ 7 ]. On the other hand, regular intake of fish-derived omega-3, i.
Interestingly, EPA and DHA play an important role in anti-inflammatory processes because they are substrates for cyclooxygenase, lipoxygenase, cytochrome P, and several other enzymes [ 9 ]. As a result, numerous lipid mediators involved in inflammatory processes are generated, including specialized pro-resolving lipid mediators SPMs , which actively resolve inflammation [ 10 ].
Several studies have pointed out that fish oils can also improve the antioxidant defense, mainly via nuclear factor erythroid 2 Nrf2 -dependent mechanisms [ 11 ] [ 12 ] [ 13 ] [ 14 ]. However, the influence of highly unsaturated fatty acids on redox homeostasis remains controversial. Therefore, a good strategy for preventing potentially detrimental health effects of the high PUFAs intake regarding oxidation may be the simultaneous consumption of omega-3 PUFAs and polyphenols. Nevertheless, it is necessary to unequivocally identify the molecular processes and biochemical pathways that can be modulated by the combination of those nutrients, determine the optimal consumption in the context of several metabolic alterations and describe potential adverse or antagonist effects, that could exist, among other concerns.
Therefore, we review the recent preclinical and clinical evidence that supports the combined use of fish-derived omega-3 PUFAs and polyphenols as nutraceuticals, for the prevention and treatment of metabolic disturbances governed by high oxidative stress and inflammation.
We aim to provide solid scientific evidence for the optimum design of nutritional strategies. The studies that have addressed this topic during the last decade are summarized in Table 1 and will be discussed more in detail in the following sections.
Table 1. Summary of the researches from the last ten years that have studied the effect of the combination between polyphenols and fish oils for improving MetS features, neurodegenerative pathologies, cancer, and other health effects. Proanthocyanidin rich grape seed extract 0. Both additive and synergistic effects on total and specific protein carbonylation in liver;effects strongly depended on the background diet; results correlated with improved insulin sensitivity and antioxidant status.
Synergistic effects: lower posterior abdominal fat wall and testicle peripheral fat;additive effects: lower cholesterol and FFA; lower adiponectin than in fish oil and more than in polyphenols; less oxidative stress than in polyphenols but more than in fish oil. Additive effects on the regulation of proteins involved in insulin signaling, glycolysis, fatty acid beta-oxidation, and endoplasmic reticulum stress. Synergistic antioxidant effect as free radical scavengers; better immunomodulatory activity at highest plant extract doses without any toxicity.
Biologically active substances-enriched BASE diet polyphenols, b-carotene, probiotics, and salmon fat ;;14 months. Regulation of gonadotrope cell activation pathway and guanylate cyclase pathway, mast cell activation, gap junction regulation, melanogenesis, and apoptosis. Additive effects of polyphenols less TG, large VLDL, and urinary 8-isoprostanes and of fish oils less postprandial chylomicron cholesterol and VLDL apolipoprotein B ; correlation lipoprotein changes and 8-isoprostanes.
Additive effects of polyphenols less plasma glucose and increased early insulin secretion and of omega-3 reduced beta-cell function and GLP Change in levels of chylomicron cholesterol and triglycerides due to omega-3; response to nutraceuticals depends on acute or chronic supplementation.
Fish oil 1. Nutraceutical cocktail polyphenols, omega-3 fatty acids, vitamin E, and selenium daily; 10—20 days. Alteration of atherosclerotic plaque composition; more prevention from neurological events associated. Resveratrol, quercetin, and apigenin 1.
Modulation of steroid hormone biosynthesis, JAK-STAT signaling pathway, ribosome, graft-versus-host disease pathways in the hippocampus;. Enhancement of cholinergic and catecholaminergic transmissions; Nrf2 activation and increased protein levels of SOD-1 and GPx. A combination of multivitamins, zinc, and omega-3 fatty acids was the most effective for improving memory and cognitive performance.
Modify premorbid characteristics; prevented injury-related deficits in longer-term behavior measures, medial prefrontal cortex spine density, and levels of Aqp4, Gfap, Igf1, Nfl, and Sirt1 expression in the prefrontal cortex. Increased working memory, hemoglobin concentration among children with anemia, decreased body mass index z score gainm, and increased lean tissue accretion with less fat; increased index of cerebral blood flow CBFi.
Mediterranean-type dietary pattern population-based case—control study, January to December , Catania, Italy. High adherence to diet inversely associated with the likelihood of prostate cancer: PCa cases consume a lower amount of vegetables, legumes, and fish.
Decreased loss of muscle cross-sectional area; an enhanced abundance of HSP70 and anabolic signaling Akt phosphorylation, p70S6K phosphorylation while reducing Nox2. Increased PUFAs and reduced SFAs in plasma; increased DHA in erythrocyte; increased blood cell polyphenol concentration in senior athletes; protects against oxidative damage but enhances nitrative damage in young athletes; gene expression of antioxidant enzymes in peripheral blood mononuclear cells after exercise in young athletes GPx, CAT, and Cu—Zn SOD.
Ineffectiveness regarding oxidative muscle damage, mitochondrial content, and protein balance and a disturbance of essential signaling pathways protein balance and mitochondriogenesis during the remobilization period. Induced autophagy by increased autolysosome formation and autophagy flux; change p62 and LC3 protein levels Cytoprotection under proteasome inhibition.
Less vascular endothelial growth factor VEGF protein expression levels and less MMP-9 activity; mitigate choroidal neovascularization and retinal disease. Omega-3 fatty acids, polyphenols, and fiber mother—neonate pairs from the prospective and observational MAMI birth cohort; 18 months, —,Spanish—Mediterranean area. Higher abundance of the Ruminococcus species in maternal gut microbiota; higher relative abundance of Faecalibacterium prausnitzii considered as a biomarker of colonic health, associated with anti-inflammatory properties; modulation of neonatal microbiota.
Several studies in both cell and animal models addressed the effects of the combination between fish oil and polyphenols in restoring the redox homeostasis that is broken in MetS. Also, the combination of apple polyphenols with fish oil in male Sprague—Dawley rats fed a high cholesterol diet improved serum and liver lipid profiles and oxidative stress markers [ 22 ].
Regarding inflammation, synergistic and additive anti-inflammatory effects between resveratrol and EPA were detected in macrophages in macrophages [ 17 ] , human peripheral blood leukocytes PBLs , and articular chondrocytes from knee NHAC-kn [ 18 ]. Moreover, the double supplemention increased monounsaturated fatty acid and polyunsaturated fatty acid-containing diacylglycerols DAG and long-chain fatty acid-containing ceramides abundances compared to the control [ 24 ].
These lipidomic profiles were correlated with the up-regulation of proteins involved in improving insulin signaling, and lipid and glucose metabolism [ 25 ]. Biochemical and biometric parameters confirmed that only the nutraceutical combination could restore insulin, leptin, and triglyceride levels to normal values [ 26 ].
Polyphenols and marine omega-3 PUFAs in combination with other biologically active substances were also evaluated in some preclinical studies. Fish oil supplemented with plant oil extracts from Schisandra chinensis and Matricaria chamomilla [ 27 ] demonstrated synergistic effects as free radical scavengers compared to controls in mice.
Brown seaweed lipids extracts resulting in less lipid peroxidation in the liver of female KK-Ay mice, even if the hepatic percentage of PUFAs increased [ 28 ]. The long-term intake of the BASE diet modulated the expression of relevant genes associated with chronic disorders in the liver of male Sprague—Dawley rats, suggesting a link between diet, reproductive system function, and aging [ 29 ]. Moreover, the anti-inflammatory AIDM mixture [ 30 ] was effective in improving lipid and inflammatory CVD risk factors in rodents, and a fish oil combined with motherwort oil demonstrated superior cardioprotective properties in rats [ 31 ].
The effects of diets rich in fish-derived omega-3 and polyphenols in subjects at high CV risk have been studied in several human trials, which reported a reduction in the postprandial lipid content of large very low-density lipoprotein VLDL and increases intermediate-density lipoprotein IDL cholesterol; LDL particles richer in triglycerides, and HDL poorer [ 32 ] [ 33 ] while decreasing oxidative stress [ 33 ] , and blood glucose, insulin secretion and postprandial glucagon-like peptide 1 levels [ 34 ].
Other lipid rearrangements in HDL were also reported [ 35 ]. Diets enriched in proanthocyanidins from cranberry juice and fish oil also improved both insulin and lipoprotein metabolisms in patients suffering from diabetes and periodontal disease [ 36 ]. Nevertheless, it has been reported that the postprandial chylomicron response to these nutraceuticals depends on supplementation time [ 37 ] , and should also be considered in this kind of nutrition strategies.
Interestingly, the statin therapy of patients suffering from CVD could be efficiently complemented with a combination of fish oils and polyphenols [ 40 ]. Several mixtures of bioactive substances and nutraceutical cocktails, all of them especially rich in polyphenols and fish oils, were also tested in human trials [ 41 ] [ 42 ] [ 43 ] , demonstrating effectiveness in ameliorating lipid profiles, inflammation and atheroscerotic events, but less action on insulin sensitivity.
The benefitial effects of combining polyphenols and fish oils on cognition alteration and neurodegenerative processes have been also investigated. Thus, resveratrol and DHA significantly altered hippocampal expression of gene associated with inflammatory responses [ 46 ]. Similar conclusions on the improvement of memory and cognitive performance were also reached in animal models feeding diets rich in those compounds and other bioactive nutrients [ 49 ]. However, results were more inconsistent in clinical trials.
Mixtures between polyphenols and omega-3 were tested in young subjects to find beneficial effects over the post-mild traumatic brain injury function in adolescent rats [ 50 ] , and seemed to improve executive function, brain health, and nutritional status in vulnerable young children at risk of undernutrition living in low-income countries [ 53 ].
The bioactivity of the combination between polyphenols and PUFAs was also tested against some types of cancers. Interestingly, some esterified phenols with omega-3 PUFAs so-called lipophenols , particularly quercetin bound to ALA, EPA and DHA reported antioxidant, anti-inflammatory, and anticarcinogenic properties in lung cells exposure to H 2 O 2 insult [ 66 ] or cigarette smoke toxicants [ 67 ].
A recent study reported that hydroxytyrosol combined with omega-3 and curcumin reduced inflammation and pain in patients with aromatase-induced musculoskeletal symptoms, as one of the side effects of the hormonal therapies for breast cancer [ 55 ]. Remarkably, several DHA and phenols conjugated increase the bioactivity of the individual compounds against breast cancer [ 68 ] , and also might prevent or inhibit the progression of triple-negative breast cancer TNBC [ 69 ] and inhibit the gelatinolytic matrix metalloproteinase MMP-9 [ 70 ].
Morever, the high adherence to diets rich in polyphenols and fish oils, such as the Mediterranean diet, was found inversely associated with the likelihood of suffering from prostate cancer [ 56 ]. As a consequence, it has been found that fish oil and curcumin mayprevent skeletal muscle atrophy [ 57 ]. Functional beverages containing these nutraceuticals seemed to protect against oxidative damage [ 58 ] and enhance the gene expression of antioxidant enzymes in peripheral blood mononuclear cells [ 59 ] in young athletes, but increasing nitrative damage [ 58 ] and the proinflammatory circulating environment in response to the exercise [ 59 ].
These heterogeneous results reflect the extremely complexyty of the redox homeostasis in skeletal muscle and the need for more investigation. Likewise, it has been reported that omega-3 and resveratrol could prevent aged retinal pigment epithelial RPE cells damage and age-related macular degeneration [ 61 ] , choroidal neovascularization [ 62 ] and they can be used for designed dermatologic diets to improve skin barrier function for the treatment of dermatitis [ 63 ].
Interestingly, several esterified phenols with DHA have shown powerful antioxidant properties and high protection activities against reactive aldehyde all-trans-retinal toxicity and photo-oxidative toxicity and constitute highly promising strategies for the prevention of retinal degeneration [ 71 ] [ 72 ] [ 73 ] [ 74 ] [ 75 ] [ 76 ].
Finally, some studies revealed that immune priming [ 64 ] and microbiota [ 65 ] in the newborn are tightly regulated by maternal diet composition, particularly polyphenols and omega-3, affecting the infant health.
The health benefits of the combination of the bioactive properties of polyphenols and fish oil have been largely supported by a growing amount of scientific evidence. Several synergistic, additive, or complementary antioxidant and anti-inflammatory effects have been consistently reported, as well as modulation of lipid and lipoprotein metabolism. Modulation of insulin signaling and gut microbiota were also found.
Nevertheless, some bioactive cocktails failed in reproducing the beneficial effects in clinical trials. The adoption of multiomic and system biology strategies, and increasing the number of clinical trials would help fully understanding how those nutraceuticals interact to each other in vivo and with the metabolism of a certain organism.
This knowledge is neccessary for the correct use of polyphenols and fish oil as part of personalized nutrition. Encyclopedia Scholarly Community. Submitted Successfully! Thank you for your contribution! You can also upload a video entry or images related to this topic. Video Upload Options Do you have a full video? Send video materials Upload full video. Confirm Are you sure to Delete? Yes No. If you have any further questions, please contact Encyclopedia Editorial Office.
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