A Human Pharmacokinetic Study

Funding: This research was supported by the Projects PID2019-103914RB-I00 and PID2019-109369RBI00 from the Ministry of Science and Innovation (MCIN/AEI/10.13039/501100011033, Spain). C.E.I.- A. is the holder of a predoctoral grant FPU18/03961 from MICIN. M.C.L.-H. is a receipt of a Juan de la Cierva Grant IJC2020-044353-I/MCIN/AEI/10.13039/501100011033/EU/PRTR.Exosomes are extracellular vesicles (EVs) that regulate intercellular signaling by transferring small RNAs, proteins, nucleic acids, lipids, and other metabolites to local or distant organs, including the brain, by crossing the blood-brain barrier. However, the transport of (poly)phenols in human EVs has not yet been described. Therefore, we aimed here to explore (i) whether resveratrol and (or) its derived metabolites are found in the cargo of human plasma exosome-containing EVs (E-EVs), (ii) when this incorporation occurs, and (iii) whether resveratrol intake stimulates the release of E-EVs. Thus, in a pharmacokinetic study, healthy volunteers (n = 16) consumed 1 capsule (420 mg resveratrol) in the evening before attending the clinic and one more capsule on the day of the pharmacokinetics. The plasma and the isolated E-EVs were analyzed using UPLC-ESI-QTOF-MS. Of 17 metabolites in the plasma, 9 were identified in the E-EVs, but not free resveratrol. The kinetic profiles of resveratrol metabolites were similar in the plasma and the E-EVs, a higher metabolite concentration being detected in the plasma than in the E-EVs. However, the plasma/E-EVs ratio decreased in the gut microbial metabolites, suggesting their better encapsulation efficiency in E-EVs. In addition, glucuronide conjugates of resveratrol, dihydroresveratrol, and lunularin were incorporated into the E-EVs more efficiently than their corresponding sulfates despite glucuronides reaching lower plasma concentrations. Notably, more E-EVs were detected 10 h after resveratrol consumption. This exploratory study provides the first evidence that (i) resveratrol metabolites are transported by E-EVs, with a preference for glucuronide vs. sulfates, (ii) the gut microbial metabolites concentration and kinetic profiles are closely similar in E-EVs and plasma, and (iii) resveratrol intake elicits E-EVs secretion. Overall, these results open new research avenues on the possible role of E-EVs in (poly)phenol health effects.publishersversionpublishe

Impact of dietary supplementation with olive and thyme phenols on alpha-tocopherol concentration in the muscle and liver of adult Wistar rats

A preliminary study to evaluate the effect of dietary supplementation with olive phenols (oleuropein, hydroxytyrosol and secoiridoids), thyme phenols and a combination of these (5 mg per kg rat weight per day) on the α-tocopherol concentrations in the muscle and liver of healthy adult Wistar rats over 21 days was conducted. In addition, the excretion of α-tocopherol through the faeces was examined. The results demonstrated that the diet supplemented with some phenolic compounds of olive and thyme increased α-tocopherol (P < 0.05) in the liver of female rats, although the α-tocopherol content in the diet of all groups was identical. In addition, a synergic effect between the olive phenols and thyme was observed. Therefore, our study indicates a protective effect of olive and thyme phenols supplemented in the diet on α-tocopherol, resulting in a higher concentration of endogenous α-tocopherol in the rat liver.This study was supported by the Spanish Ministry of Education and Science (AGL2012-40144-C03-03 project), by the Spanish Ministry of Education, Culture and Sport through the ‘Formación Profesorado Universitario’ D. Bars-Cortina grant (FPU014/02902), and by the University of Lleida through the M.C. López de las Hazas grant

The emergent role of mitochondrial RNA modifications in metabolic alterations

Mitochondrial epitranscriptomics refers to the modifications occurring in all the different RNA types of mitochondria. Although the number of mitochondrial RNA modifications is less than those in cytoplasm, substantial evidence indicates that they play a critical role in accurate protein synthesis. Recent evidence supported those modifications in mitochondrial RNAs also have crucial implications in mitochondrial-related diseases. In the light of current knowledge about the involvement, the association between mitochondrial RNA modifications and diseases arises from studies focusing on mutations in both mitochondrial and nuclear DNA genes encoding enzymes involved in such modifications. Here, we review the current evidence available for mitochondrial RNA modifications and their role in metabolic disorders, and we also explore the possibility of using them as promising targets for prevention and early detection. Finally, we discuss future directions of mitochondrial epitranscriptomics in these metabolic alterations, and how these RNA modifications may offer a new diagnostic and theragnostic avenue for preventive purposes.This work was supported by the European Cooperation in Science and Technology (COST) Action CA16120 (European Epitranscriptomic Network). This work was also supported by “Centros de Investigación En Red” (CIBER, CB06/03/0018) of the “Instituto de Salud Carlos III” (ISCIII) (PI18/01399), and co-financed by the European Regional Development Fund (FEDER). This work was also supported by the Agencia Estatal de Investigación and European FEDER Funds (PID2019-109369RB-100 and AGL2018-78922-R). HB is supported by a predoctoral fellowship (“Plan Propio IBIMA 2020 A.1 Contratos predoctorales”, Ref.: predoc20_002). M.M.G. was the recipient of the Nicolas Monardes Programme from the “Servicio Andaluz de Salud, Junta de Andalucia”, Spain (RC-0001-2018 and C-0029-2014). funding for open access charge: Universidad de Málag

Pulsed electric field increases the extraction yield of extra virgin olive oil without loss of its biological properties

Introduction: Pulsed electric field (PEF) has been used for improving extraction of extra virgin olive oil (EVOO). However, the biological changes induced by the consumption of pulsed electric field-obtained extra virgin olive oil (PEFEVOO) have not been studied yet. Materials and methods: EVOO oils from Empeltre variety were prepared by standard (STD) cold pressure method involving crushing of the olives, malaxation and decanting and by this procedure including an additional step of PEF treatment. Chemical analyses of EVOO oils were done. Male and female Apoe-deficient mice received diets differing in both EVOOs for 12 weeks, and their plasma, aortas and livers were analyzed. Results: PEF application resulted in a 17% increase in the oil yield and minimal changes in chemical composition regarding phytosterols, phenolic compounds and microRNA. Only in females mice consuming PEF EVOO, a decreased plasma total cholesterol was observed, without significant changes in atherosclerosis and liver steatosis. Conclusion: PEF technology applied to EVOO extraction maintains the EVOO quality and improves the oil yield. The equivalent biological effects in atherosclerosis and fatty liver disease of PEF-obtained EVOO further support its safe use as a food