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The popularity and increasing demand for botanicals are correlated with the growth of nutraceuticals and new functional products on the market. Unfortunately, also fraudulent practices are increasi...

The low oxidative stability of polyunsaturated fatty acids (PUFA) in omega-3 supplements may cause the formation of compounds that may have negative healthy effects. Extra virgin olive oil (EVOO) contains high content of monounsaturated fatty acids (MUFA) and polyphenols, which might improve PUFA oxidative stability when combined with vegetable oils enriched in them. In order to prevent the formation of oxidized compounds and improve the shelf-life of PUFA, different proportions of EVOO (enriched in oleic acid and polyphenols) and algae oil (AO) were studied. For this purpose, both pure oils combined in different proportions were stored under accelerated degradation conditions (40 and 55 °C) for 70 days. Correlations and significant changes in levels of fatty acids composition, phenolic components and oxidation rates during storage time were studied. Throughout storage, higher EVOO quantity at the final mixture was related with less PUFA degradation, where a 27.53% decrease in PUFA of AO passed to less than 12% in a resulting oil of at least 75% of EVOO. PUFA concentration correlated with the formation of secondary peroxides, while MUFA content from EVOO produced a reduction in PUFA degradation. In addition, high secoiridoid levels in mixtures decreased the hydrolysis of triglycerides over the time.

Aging is associated with a progressive decline in skeletal muscle mass, strength and function (sarcopenia). We have investigated whether a mixture of algae oil (25%) and extra virgin olive oil (75%) could exert beneficial effects on sarcopenia. Young (3 months) and old (24 months) male Wistar rats were treated with vehicle or with the oil mixture (OM) (2.5 mL/kg) for 21 days. Aging decreased gastrocnemius weight, total protein, and myosin heavy chain mRNA. Treatment with the OM prevented these effects. Concomitantly, OM administration decreased the inflammatory state in muscle, it prevented the increase of pro-inflammatory interleukin-6 (IL-6) and the decrease in anti-inflammatory interleukin-10 (IL-10) in aged rats. The OM was not able to prevent aging-induced alterations in either the insulin-like growth factor I/protein kinase B (IGF-I/Akt) pathway or in the increased expression of atrogenes in the gastrocnemius. However, the OM prevented decreased autophagy activity (ratio protein 1A/1B-light chain 3 (LC3b) II/I) induced by aging and increased expression of factors related with muscle senescence such as histone deacetylase 4 (HDAC-4), myogenin, and IGF-I binding protein 5 (IGFBP-5). These data suggest that the beneficial effects of the OM on muscle can be secondary to its anti-inflammatory effect and to the normalization of HDAC-4 and myogenin levels, making this treatment an alternative therapeutic tool for sarcopenia.

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-derived products, such as virgin olive oil (EVOO) and/or olive leaf extracts (OLE), exert anti-inflammatory, insulin-sensitizing and antihypertensive properties and may be useful for stabilizing omega 3 fatty acids (n-3 PUFA) due to their high content in antioxidant compounds. In this study, the addition of OLE 4:0.15 (w/w) to a mixture of algae oil (AO) rich in n-3 PUFA and EVOO (25:75, w/w) prevents peroxides formation after 12 months of storage at 30◦C. Furthermore, the treatment with the oil mixture (2.5 mL/Kg) and OLE (100 mg/Kg) for 24 month old Wistar rats in 21 days improved the lipid profile, increased the HOMA-IR and decreased the serum levels of miRNAs 21 and 146a. Treatment with this new nutraceutical also prevented age-induced insulin resistance in the liver, gastrocnemius and visceral adipose tissue by decreasing the mRNA levels of inflammatory and oxidative stress markers. Oil mixture + OLE also attenuated the age-induced alterations in vascular function and prevented muscle loss by decreasing the expression of sarcopenia-related markers. In conclusion, treatment with a new nutraceutical based on a mixture of EVOO, AO and OLE is a useful strategy for improving the stability of n-3 PUFA in the final product and to attenuate the cardiometabolic and muscular disorders associated with aging., This project was funded by the call “Doctorados Industriales 2017” (IND2017/BIO7701), a grant from the 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 Ph.D. student (Daniel González- Hedström) for three years by the company (Pharmactive Biotech Products S.L.). The Community of Madrid also funded the contract of María de la Fuente-Fernández through the Youth Employment Program (PEJ-2018-AI/SAL-11315)

Aging is associated with increased visceral adiposity and a decrease in the amount of brown adipose tissue and muscle mass, known as sarcopenia, which results in the development of metabolic alterations such as insulin resistance. In this study, we aimed to analyze whether 3-week supplementation with a phenolic-rich olive leaf extract (OLE) to 24 months-old male Wistar rats orally (100 mg/kg) attenuated the aging-induced alterations in body composition and insulin resistance. OLE treatment increased brown adipose tissue and attenuated the aging-induced decrease in protein content and gastrocnemius weight. Treatment with OLE prevented the aging-induced increase in the expression of PPAR-γ in visceral and brown adipose tissues, while it significantly increased the expression of PPAR-α in the gastrocnemius of old rats and reduced various markers related to sarcopenia such as myostatin, HDAC-4, myogenin and MyoD. OLE supplementation increased insulin sensitivity in explants of gastrocnemius and epididymal visceral adipose tissue from aged rats through a greater activation of the PI3K/Akt pathway, probably through the attenuation of inflammation in both tissues. In conclusion, supplementation with OLE prevents the loss of muscle mass associated with aging and exerts anti-inflammatory and insulin-sensitizing effects on adipose tissue and skeletal muscle.

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).

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.

Aging is one of the major risk factors for suffering cardiovascular and metabolic diseases. Due to the increase in life expectancy, there is a strong interest in the search for anti-aging strategies to treat and prevent these aging-induced disorders. Both omega 3 polyunsaturated fatty acids (&omega, 3 PUFA) and extra virgin olive oil (EVOO) exert numerous metabolic and cardiovascular benefits in the elderly. In addition, EVOO constitutes an interesting ingredient to stabilize &omega, 3 PUFA and decrease their oxidation process due to its high content in antioxidant compounds. &omega, 3 PUFA are commonly obtained from fish. However, more ecological and sustainable sources, such as algae oil (AO) can also be used. In this study, we aimed to study the possible beneficial effect of an oil mixture composed by EVOO (75%) and AO (25%) rich in &omega, 3 PUFA (35% docosahexaenoic acid (DHA) and 20% eicosapentaenoic acid (EPA)) on the cardiometabolic alterations associated with aging. For this purpose, young (three months old) and old (24 months old) male Wistar rats were treated with vehicle or with the oil mixture (2.5 mL/kg) for 21 days. Treatment with the oil mixture prevented the aging-induced increase in the serum levels of saturated fatty acids (SFA) and the aging-induced decrease in the serum concentrations of mono-unsaturated fatty acids (MUFA). Old treated rats showed increased serum concentrations of EPA and DHA and decreased HOMA-IR index and circulating levels of total cholesterol, insulin and IL-6. Treatment with the oil mixture increased the mRNA levels of antioxidant and insulin sensitivity-related enzymes, as well as reduced the gene expression of pro-inflammatory markers in the liver and in cardiac and aortic tissues. In addition, the treatment also prevented the aging-induced endothelial dysfunction and vascular insulin resistance through activation of the PI3K/Akt pathway. Moreover, aortic rings from old rats treated with the oil mixture showed a decreased response to the vasoconstrictor AngII. In conclusion, treatment with a mixture of EVOO and AO improves the lipid profile, insulin sensitivity and vascular function in aged rats and decreases aging-induced inflammation and oxidative stress in the liver, and in the cardiovascular system. Thus, it could be an interesting strategy to deal with cardiometabolic alterations associated with aging

[Background]: Saffron has antidepressant and anxiolytic effects in adults with mild-to-moderate depression. However, this is the first study examining its mood-related effects in teenagers. [Methods]: In this 8-week, randomised, double-blind, placebo-controlled study, youth aged 12–16 years, with mild-to-moderate anxiety or depressive symptoms were given tablets containing placebo or a saffron extract (affron, 14 mg b.i.d). The youth and parent versions of the Revised Child Anxiety and Depression Scale (RCADS) were used as outcome measures. [Results]: 80 participants were enrolled and 68 completed the study. Based on youth self-reports, affron was associated with greater improvements in overall internalising symptoms (p = 0.049), separation anxiety (p = 0.003), social phobia (p = 0.023), and depression (p = 0.016). Total internalising scores decreased by an average of 33% compared to 17% in the placebo group (p = 0.029). However, parental reports of improvements were inconsistent as mean improvements in RCADS scores were greater in the saffron group (40% vs 26%) (p = 0.026), although no other significant differences were identified. affron was well-tolerated and there was a trend of reduced headaches in participants on the active treatment. [Limitations]: The use of a self-report instrument, limited study duration, single treatment dose, and non-clinical sample used in this study limit the generalisability of study findings. [Conclusion]: The administration of a standardised saffron extract (affron) for 8 weeks improved anxiety and depressive symptoms in youth with mild-to-moderate symptoms, at least from the perspective of the adolescent. However, these beneficial effects were inconsistently corroborated by parents., This study was funded by Pharmactive Biotech Products SL. The authors gratefully acknowledge Pharmactive Biotech Products SL Company for funding the project.

In recent years phytotherapy has been explored as a source for alternative treatments for mood disorders. One potential candidate is saffron (Crocus sativus L.), whose main bioactive components are crocins and safranal.The aim of this study was to investigate the efficacy of affronIn this 3 arm study, 128 participants self-reporting low mood but not diagnosed with depression, were given affronAnalysis indicated a significant decrease in negative mood and symptoms related to stress and anxiety at a 28mg/day dose (with a significant difference between 28mg/day and placebo on the POMS Total Mood Disturbance scale, p0.001, d=-1.10), but no treatment effect at the 22mg/day dose.The main weaknesses of this investigation were found in the self-reporting nature of both the screening and the testing.affron

[Background]: In recent years phytotherapy has been explored as a source for alternative treatments for mood disorders. One potential candidate is saffron (Crocus sativus L.), whose main bioactive components are crocins and safranal. [Objectives]: The aim of this study was to investigate the efficacy of affron, a standardised stigmas extract from Crocus sativus L. for improving mood, stress, anxiety and sleep quality in healthy adults. [Methods]: In this 3 arm study, 128 participants self-reporting low mood but not diagnosed with depression, were given affron at 28 mg/day, 22 mg/day, or a placebo treatment in a randomized, double-blind, placebo-controlled trial for 4 weeks. Mood was measured at baseline and at the end of the study, using the POMS (primary outcome measure) and PANAS questionnaires, and the DASS-21 scale. Sleep was monitored using Sleep Quality Index (PSQI). [Results]: Analysis indicated a significant decrease in negative mood and symptoms related to stress and anxiety at a 28 mg/day dose (with a significant difference between 28 mg/day and placebo on the POMS Total Mood Disturbance scale, p, This study was funded by Pharmactive Biotech Products SL.

Aged black garlic (ABG) exerts metabolic and cardiovascular beneficial effects. The aim of this work was to analyse the in vitro cardiovascular effects of an ABG extract enriched in S-allyl-cysteine and polyphenols (ABG10+) in Sprague-Dawley rats. Hearts were pre-treated either with ABG10+ or vehicle and subjected to 30 min ischaemia followed by 45 min reperfusion (IR) using the Langendorff technique. Segments of aorta and tail artery were used for inflammation/oxidative stress and vascular reactivity experiments respectively in presence/absence of ABG10+. ABG10+ induced a nitric oxide (NO) dependent vasodilating effect in tail artery segments and directly increased the release of NO in aorta segments. In the heart, ABG10+ induced a relaxing effect on coronary arteries before and after IR and prevented the IR induced decrease in myocardial contractility. Functional changes were associated with increased expression of both pro- and antioxidant and pro- and anti-inflammatory markers in the myocardium and in aorta., This work has been funded by Pharmactive Biotech Products SL (Madrid, Spain).