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Seasonal flu is caused by influenza infection, a virus that spreads easily in human population with periodical epidemic outbreaks. The high mutational rate of influenza viruses leads to the emergence of strains resistant to the current treatments. Due to that, scientific research is focusing on the development of new anti-influenza agents as alternative or complementary treatments. Olive tree (Olea europaea L.) has been a source of ancestral remedies due to its antimicrobial activity. Thus, the aim of this study was to test the anti-influenza activity of a standardized olive leaf extract rich in elenolic acid (EA), Isenolic®, compared with oseltamivir. Isenolic® extract was characterized by High Performance Liquid Chromatography (HPLC)-Mass Spectrometry and its content in EA was determined by HPLC. Cytotoxicity, viral neuraminidase inhibitor activity and cell viability protection against influenza infection of Isenolic® were tested in vitro using sialic acid overexpressing Madin-Darby Canine Kidney cells. Isenolic® formulations showed a 4% and 8% dry basis. Oseltamivir and Isenolic® extracts showed anti-influenza activity. The 8% Isenolic® formulation showed a dose-dependent neuraminidase inhibitor activity higher than the 4% formulation, and preserved cell viability under viral infection. Thus, Isenolic® become a promising natural alternative to existing influenza treatments.

Olive leaves are rich in bioactive substances which exert anti-inflammatory, antioxidant, insulin-sensitizing and antihypertensive effects. The aim of this study was to analyze the possible beneficial effects of an olive leaf extract (OLE) rich in secoiridoids and phenolic compounds on the aging-induced metabolic and vascular alterations. Three experimental groups of rats were used: 3-month-old rats, 24-month-old rats and 24-month-old rats supplemented 21 days with OLE (100 mg/kg). Administration of OLE to aged rats decreased the weight of adrenal glands and prevented the aging-induced loss of body weight and muscle mass. In the serum, OLE reduced the circulating levels of LDL-cholesterol and IL-6 and increased the concentrations of leptin and adiponectin. In the liver OLE attenuated the decreased gene expression of SOD-1, GSR, GCK and GSK-3β and reduced the aging-induced overexpression of NOX-4, Alox-5, iNOS and TNF-α. In aorta segments, OLE prevented endothelial dysfunction and vascular insulin resistance and improved vasoconstriction in response to KCl and NA. Improvement in vascular function was associated with the attenuation of the alterations in the gene expression of COX-2, IL-6, GPx, NOX-1 and IL-10. In conclusion, OLE exerts anti-inflammatory and antioxidant effects in aged rats and attenuates the alterations in vascular function associated with aging., This project was funded by the call “Doctorados Industriales 2017” (IND2017/BIO7701), a grant from Community of Madrid (Spain). This program aims to promote the effective collaboration between Universities and Companies and provides funding for both, the development of the research project in the University and the Company, and to hire a PhD student (Daniel González-Hedström) over a three-year period by the Company (Pharmactive Biotech Products S.L.). Community of Madrid also funded the contract of María de la Fuente-Fernández through the Youth Employment Program (PEJ-2018-AI/SAL-11315).

This article belongs to the Special Issue Integrated Membrane Systems and Processes., The effectiveness of a preparative integrated ultrafiltration/solid-phase extraction (UF/SPE) process for purification of oligomeric procyanidins (OPCs) from a crude grape seed extract (GSE) was studied for the first time. The separation of OPCs from polymeric procyanidins (PPCs) by UF was very efficient. The membrane showed an acceptable filtration flux of 6 to 3.5 L/h·m2 at 0.5 bar of transmembrane pressure and 95% recovery of its water flux after chemical cleaning. The process was scalable to a pilot scale. The separation of very polar and ionic species from OPCs by SPE (XAD7HP and XAD16 resins) was also very good, but both adsorbents lost their retention capacities quickly, due probably to irreversible retention of OPCs/PPCs. Even though the global purification of OPCs by the integrated UF/SPE process allowed the recovery of 24.2 g of highly purified OPCs (83% purity) from 14.4 L of crude grape seed extract, the use of these adsorbents for further purification of the OPCs was very limited., This research was funded by MINECO (Spain), Project HELIFOOD (AGL2017-89566-R).

The incidence of metabolic syndrome (MetS) is increasing worldwide which makes necessary the finding of new strategies to treat and/or prevent it. The aim of this study was to analyze the possible beneficial effects of a carob fruit extract (CSAT+&reg, ) on the cardiometabolic alterations associated with MetS in mice. 16-week-old C57BL/6J male mice were fed for 26 weeks either with a standard diet (chow) or with a diet rich in fats and sugars (HFHS), supplemented or not with 4.8% of CSAT+&reg, CSAT+&reg, supplementation reduced blood glucose, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and circulating levels of total cholesterol, low-density lipoprotein (LDL) cholesterol (LDL-c), insulin, and interleukin-6 (IL-6). In adipose tissue and skeletal muscle, CSAT+&reg, prevented MetS-induced insulin resistance, reduced macrophage infiltration and the expression of pro-inflammatory markers, and up-regulated the mRNA levels of antioxidant markers. Supplementation with CSAT+&reg, prevented MetS-induced hypertension and decreased the vascular response of aortic rings to angiotensin II (AngII). Moreover, treatment with CSAT+&reg, attenuated endothelial dysfunction and increased vascular sensitivity to insulin. In the heart, CSAT+&reg, supplementation reduced cardiomyocyte apoptosis and prevented ischemia-reperfusion-induced decrease in cardiac contractility. The beneficial effects at the cardiovascular level were associated with a lower expression of pro-inflammatory and pro-oxidant markers in aortic and cardiac tissues.

There are few studies about the pharmacokinetics of the low-molecular mass carotenoids crocetin or crocin isomers from saffron (Crocus sativus L.). None has been performed with a galenic preparation of a standardised saffron extract. The aim of the present research work was to study the effect of in vitro digestion process on the main bioactive components of saffron extract tablets and the corresponding pharmacokinetic parameters in humans. Pharmacokinetics were calculated collecting blood samples every 30 min during the first 3 h and at 24 h after administration of two different concentrations (56 and 84 mg of the saffron extract) to 13 healthy human volunteers. Additionally, an in vitro digestion process was performed in order to determine the bioaccessibility of saffron main bioactive compounds. Identification and quantification analysis were performed by HPLC-PAD/MS. Digestion resulted in 40% of bioaccesibility for crocin isomers, whereas, safranal content followed an opposite trend increasing about 2 folds its initial concentration after the digestion process. Crocetin in plasma was detected in a maximum concentration (Cmax) in blood between 60 and 90 min after oral consumption with dose-dependent response kinetics, showing that crocin isomers from galenic preparation of saffron extract are rapidly transformed into crocetin. The results showed that this tested galenic form is an efficient way to administer a saffron extract, since the observed crocetin Cmax was similar and more quickly bioavailable than those obtained by other studies with much higher concentrations of crocetin., The authors gratefully acknowledge the Pharmactive Biotech Products, SL Company, for funding the project and supplying affron®, LIPA Pharmaceuticals for manufacturing the tablets, and RDC Clinical for their management of the clinical trial.

Aged black garlic (ABG) is a functional food with antioxidant and anti-inflammatory properties. Recent studies also report its beneficial metabolic effects in a context of obesity or diabetes, although the mechanisms involved are poorly understood. The aim of this work was to analyze the effects of an ABG extract in the vascular and metabolic alterations induced by a high-fat/sucrose diet in rats. For this purpose, male Sprague&ndash, Dawley rats were fed either a standard chow (controls, n = 12) or a high-fat/sucrose diet (HFD, n = 24) for 16 weeks. From week 8 on, half of the HFD rats were treated with a commercial ABG extract concentrated in S-allyl cysteine and melanoidins (ABG10+&reg, 250 mg/kg daily by gavage, 5 mL/kg). ABG10+&reg, treated rats showed lower mean caloric intake, body weight, triglycerides, low density lipoprotein cholesterol (LDL-c), insulin and leptin serum concentrations and higher high density lipoprotein cholesterol (HDL-c) and adiponectin serum concentrations than non-treated rats. In the hypothalamus, ABG10+&reg, treatment induced an increase in the gene expression of proopiomelanocortin (POMC) and a decrease in leptin receptor (ObR) mRNA levels. No significant changes were found in visceral adipose tissue except for an overexpression of &beta, 3-adrenergic receptor (&beta, 3-ADR) in ABG-treated rats. In subcutaneous adipose tissue, ABG10+&reg, treatment decreased adipose weight and downregulated the gene expression of PPAR-&gamma, LPL, ObR and HSL. In brown adipose tissue, an overexpression of InsR, GLUT-4, UCP-1 and &beta, 3-ADR in ABG10+&reg, treated rats was found, whereas PPAR-&gamma, mRNA levels were significantly decreased. Regarding vascular function, ABG10+&reg, treatment attenuated the obesity-induced vasoconstriction in response to potassium chloride both in presence/absence of perivascular adipose tissue (PVAT). On the contrary, aorta segments from ABG-treated rats showed and improved relaxation in response to acetylcholine only when PVAT was present, with this fact possible being related to the decreased gene expression of proinflammatory cytokines in this tissue. In conclusion, ABG10+&reg, administration partially improves the metabolic and vascular alterations induced by a high-fat/high-sucrose diet in rats through modifications in the gene expression of proteins and neuropeptides involved in inflammation, fat metabolism and food intake regulation. Further studies are required to assess the bioavailability of ABG between rats and humans.