Nutri-epigenetic Effects of Phenolic Compounds from Extra Virgin Olive Oil: A Systematic Review

: Dietary components can induce epigenetic changes through DNA methylation, histone modification, and regulation of microRNAs (miRNAs). Studies of diet-induced epigenetic regulation can inform anticipatory trials and fine-tune public health guidelines. We systematically reviewed data on the effect of extra virgin olive oil (EVOO) and its phenolic compounds (OOPCs) on the epigenetic landscape. We conducted a literature search using PubMed, Scopus, and Web of Science databases and scrutinized published evidence. After applying selection criteria (e.g., inclusion of in vitro, animal, or human studies supplemented with EVOO or its OOPCs), we thoroughly reviewed 51 articles, and the quality assessment was performed using the revised Cochrane risk of bias tool. The results show that both EVOO and its OOPCs can promote epigenetic changes capable of regulating the expression of genes and molecular targets involved in different metabolic processes. For example, oleuropein (OL) may be an epigenetic regulator in cancer; and hydroxytyrosol (HT) modulates the expression of miRNAs involved in the development of cancer, cardiovascular, and neurodegenerative diseases. We conclude that EVOO and its OPPCs can regulate gene expression by modifying epigenetic mechanisms and impact human pathophysiology. A full elucidation of the epigenetics effects of EVOO and its OOPCs may contribute to developing different pharma-nutritional strategies that exploit them as epigenetic agents

Therapeutic potential of plant-derived extracellular vesicles as nanocarriers for exogenous miRNAs

Cell-to-cell communication strategies include extracellular vesicles (EVs) in plants and animals. The bioactive molecules in a diet rich in vegetables and fruits are associated with disease-preventive effects. Plant-derived EVs (PDEVs) are biogenetically and morphologically comparable to mammalian EVs and transport bioactive molecules, including miRNAs. However, the biological functions of PDEVs are not fully understood, and standard isolation protocols are lacking. Here, PDEVs were isolated from four foods with a combination of ultracentrifugation and size exclusion chromatography, and evaluated as vehicles for enhanced transport of synthetic miRNAs. In addition, the role of food-derived EVs as carriers of dietary (poly)phenols and other secondary metabolites was investigated. EVs from broccoli, pomegranate, apple, and orange were efficiently isolated and characterized. In all four sources, 4 miRNA families were present in tissues and EVs. miRNAs present in broccoli and fruit-derived EVs showed a reduced RNase degradation and were ferried inside exposed cells. EVs transfected with a combination of ath-miR159a, ath-miR162a-3p, ath-miR166b-3p, and ath-miR396b-5p showed toxic effects to human cells, as did natural broccoli EVs alone. PDEVs transport trace amounts of phytochemicals, including flavonoids, anthocyanidins, phenolic acids, or glucosinolates. Thus, PDEVs can act as nanocarriers for functional miRNAs that could be used in RNA-based therapy