Wine\u2019s Phenolic Compounds and Health: A Pythagorean View

In support of the J curve that describes the association between wine consumption and all-cause mortality, researchers and the lay press often advocate the health benefits of (poly)phenol consumption via red wine intake and cite the vast amount of in vitro literature that would corroborate the hypothesis. Other researchers dismiss such evidence and call for total abstention. In this review, we take a skeptical, Pythagorean stance and we critically try to move the debate forward by pointing the readers to the many pitfalls of red wine (poly)phenol research, which we arbitrarily treat as if they were pharmacological agents. We conclude that, after 30 years of dedicated research and despite the considerable expenditure, we still lack solid, “pharmacological”, human evidence to confirm wine (poly)phenols’ biological actions. Future research will eventually clarify their activities and will back the current recommendations of responsibly drinking moderate amounts of wine with meals

Pharma-Nutritional Properties of Olive Oil Phenols. Transfer of New Findings to Human Nutrition

The Mediterranean diet has been long associated with improved cardiovascular prognosis, chemoprevention, and lower incidence of neurodegeneration. Of the multiple components of this diet, olive oil stands out because its use has historically been limited to the Mediterranean basin. The health benefits of olive oil and some of its components are being rapidly decoded. In this paper we review the most recent pharma-nutritional investigations on olive oil biophenols and their health effects, chiefly focusing on recent findings that elucidate their molecular mechanisms of action

Breast milk microRNAs harsh journey towards potential effects in infant development and maturation. Lipid encapsulation can help

The possibility that diet-derived miRNAs survive the gastrointestinal tract and exert biological effects in target cells is triggering considerable research in the potential abilities of alimentary preventive and therapeutic approaches. Many validation attempts have been carried out and investigators disagree on several issues. The barriers exogenous RNAs must surpass are harsh and adequate copies must reach target cells for biological actions to be carried out. This prospect opened a window for previously unlikely scenarios concerning exogenous non-coding RNAs, such as a potential role for breast milk microRNAs in infants' development and maturation. This review is focused on the thorny path breast milk miRNAs face towards confirmation as relevant role players in infants' development and maturation, taking into consideration the research carried out so far on the uptake, gastrointestinal barriers and potential biological effects of diet-derived miRNAs. We also discuss the future pharmacological and pharma-nutritional consequences of appropriate miRNAs research

Proteomic evaluation of mouse adipose tissue and liver following hydroxytyrosol supplementation

Hydroxytyrosol (HT) is the primary phenolic compound of olives, virgin olive oil, and their byproducts. Proteomic analysis of metabolically active tissues helps elucidating novel mechanisms of action and potential targets in cardiometabolic disease. Thus, we aimed at determining the impact of long-term HT supplementation on the proteome of adipose and liver tissue, in mice

An overview of the pharmacology of olive oil and its active ingredients

In addition to providing organoleptic traits, olive oil's minor components, most phenolic in nature, are endowed with pharmacological/pharma-nutritional properties that are the subject of active research worldwide. Based on our >25 years of experience in this field, we critically focus on what we believe are the most pharmacologically prominent actions of olive oil's constituents. Most of the effects are due to extra virgin olive oil's phenolic molecules such as hydroxytyrosol and oleocanthal (which are often miscategorized as in vivo antioxidants) and concern the cardiovascular system. Other potentially salubrious activities are still to be investigated in depth. We conclude that - in the context of a proper diet that includes high-quality products - the use of high-quality olive oil contributes to achieving and sustaining overall health

One-week administration of hydroxytyrosol to humans does not activate Phase II enzymes

The notion that (poly)phenols act as direct free radical scavengers is being challenged by mere chemical and biochemical considerations such as bioavailability and intracellular concentrations. An alternative hypothesis that is gaining considerable traction is that (poly)phenols are processed by the body as xenobiotics via the Keap1/Nrf2/ARE signaling axis, leading to the induction of Phase II enzymes. However, there are no solid human data to confirm this interesting supposition. In this study, we tested the activities of hydroxytyrosol (HT) on Phase II enzymes expression in a double-blind, randomized, placebo-controlled study. We tested two HT doses, i.e. 5 and 25mg/d, vs. placebo following a Latin square design. We report that HT is well tolerated but does not significantly modify Phase II enzyme expression in peripheral blood mononuclear cells. Moreover, we were unable to record significant effects on a variety of surrogate markers of cardiovascular disease such as lipid profile and inflammation and oxidation markers. Available evidence indicates that the hormesis hypothesis that (poly)phenols activate Phase II enzymes requires solid human confirmation that might be provided by future trials. This study is registered at ClinicalTrials.gov (identifier: NCT02273622)

Modulation of miRNA expression in aged rat hippocampus by buttermilk and krill oil

The increasing incidence of age-induced cognitive decline justifies the search for complementary ways of prevention or delay. We studied the effects of concentrates of phospholipids, sphingolipids, and/or 3-n fatty acids on the expression of genes or miRNAs related to synaptic activity and/or neurodegeneration, in the hippocampus of aged Wistar rats following a 3-month supplementation. The combination of two phospholipidic concentrates of krill oil (KOC) and buttermilk (BMFC) origin modulated the hippocampal expression of 119 miRNAs (11 were common to both BMFC and BMFC + KOC groups). miR-191a-5p and miR-29a-3p changed significantly only in the BMFC group, whereas miR-195-3p and miR-148a-5p did so only in the combined-supplemented group. Thirty-eight, 58, and 72 differentially expressed genes (DEG) were found in the groups supplemented with KOC, BMFC and BMFC + KOC, respectively. Interaction analysis unveiled networks of selected miRNAs with their potential target genes. DEG found in the KOC and BMFC groups were mainly involved in neuroactive processes, whereas they were associated with lysosomes and mRNA surveillance pathways in the BMFC + KOC group. We also report a significant reduction in hippocampal ceramide levels with BMFC + KOC. Our results encourage additional in-depth investigations regarding the potential beneficial effects of these compounds

Hydroxytyrosol supplementation modulates the expression of miRNAs in rodents and in humans

Dietary microRNAs (miRNAs) modulation could be important for health and wellbeing. Part of the healthful activities of polyphenols might be due to a modulation of miRNAs' expression. Among the most biologically active polyphenols, hydroxytyrosol (HT) has never been studied for its actions on miRNAs. We investigated whether HT could modulate the expression of miRNAs in vivo. We performed an unbiased intestinal miRNA screening in mice supplemented (for 8 weeks) with nutritionally relevant amounts of HT. HT modulated the expression of several miRNAs. Analysis of other tissues revealed consistent HT-induced modulation of only few miRNAs. Also, HT administration increased triglycerides levels. Acute treatment with HT and in vitro experiments provided mechanistic insights. The HT-induced expression of one miRNA was confirmed in healthy volunteers supplemented with HT in a randomized, double-blind and placebo-controlled trial. HT consumption affects specific miRNAs' expression in rodents and humans. Our findings suggest that the modulation of miRNAs' action through HT consumption might partially explain its healthful activities and might be pharmanutritionally exploited in current therapies targeting endogenous miRNAs. However, the effects of HT on triglycerides warrant further investigations

Intestinal Lipid Metabolism Genes Regulated by miRNAs

MicroRNAs (miRNAs) crucial roles in translation repression and post-transcriptional adjustments contribute to regulate intestinal lipid metabolism. Even though their actions in different metabolic tissues have been elucidated, their intestinal activity is yet unclear. We aimed to investigate intestinal miRNA-regulated lipid metabolism-related genes, by creating an intestinal-specific Dicer1 knockout (Int-Dicer1 KO) mouse model, with a depletion of microRNAs in enterocytes. The levels of 83 cholesterol and lipoprotein metabolism-related genes were assessed in the intestinal mucosa of Int-Dicer1 KO and Wild Type C57BL/6 (WT) littermates mice at baseline and 2 h after an oral lipid challenge. Among the 18 genes selected for further validation, Hmgcs2, Acat1 and Olr1 were found to be strong candidates to be modulated by miRNAs in enterocytes and intestinal organoids. Moreover, we report that intestinal miRNAs contribute to the regulation of intestinal epithelial differentiation. Twenty-nine common miRNAs found in the intestines were analyzed for their potential to target any of the three candidate genes found and validated by miRNA-transfection assays in Caco-2 cells. MiR-31-5p, miR99b-5p, miR-200a-5p, miR-200b-5p and miR-425-5p are major regulators of these lipid metabolism-related genes. Our data provide new evidence on the potential of intestinal miRNAs as therapeutic targets in lipid metabolism-associated pathologies