Bioaccessibility and Pharmacokinetics of a Commercial Saffron (Crocus sativus L.) Extract

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 crocetinThe 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 tria

Quantitative mineral resource assessment of undiscovered porphyry copper resources in South America

A quantitative resource assessment to be published this fall identifies and evaluates 26 tracts in South America where the geology isconsidered permissive for the occurrence of porphyry copper deposits. For each tract, information is provided on: (1) the rationale fordelineating the tract, (2) examples of important deposits in the tract, (3) the rationale for choosing the mineral deposit model used forthe assessment, (4) exploration history, and (5) expected spatial distribution of undiscovered deposits in the tract. The scale used toevaluate geologic information and define tracts is 1:1,000,000. There are about 600 million tonnes of copper in known porphyry copper deposits in South America. This study estimates there areapproximately 720 million tonnes of additional copper in undiscovered porphyry copper deposits, yielding a combined endowment ofabout 1.3 billion tonnes of copper. There are about 69 known porphyry copper deposits using the criteria adopted here to define a well-explored deposit. This study estimates that a mean of about 140 deposits remain to be found. In other words, about twice as manynew deposits might be found as have already been found. Overall, deposit densities in South America are comparable to those in therest of the world but differ in important details that are reflected in mapped distributions of deposits, metal densities, and percentagesof undiscovered deposits in each tract. The deposits in the tracts that include Chuquicamata and El Teniente are significantly larger intonnage and grade and are reported in a separate model that is more representative of their characteristics. The results of theassessment afirm that not all porphyry copper deposits in South America are located in the Andes. Geologic indications support thepresence of undiscovered deposits in Patagonia as well as the Amazon of Brazil. A preliminary 1:4,000,000 map of the 26 tracts will bedisplayed

A preliminary quantitative mineral resource assessment of undiscovered porphyry copper resources in the Andes mountains of South America

Quantitative information on the probable locations and amounts of undiscovered porphyry copper resources of the world is important to international exploration managers, land-use and environmental planners, economists, and policy makers. The U.S. Geological Survey is organizing and facilitating a cooperative assessment, in collaboration with interested geological surveys and geological organizations, of the likely global distribution, quantity, and quality of selected undiscovered nonfuel mineral resources. This report on undiscovered porphyry copper deposits of the Andes Mountains was produced jointly with the geological surveys of Argentina, Chile, Colombia, and Peru, and is a summary of the more extensive report (>300 pages) that will be published soon. Reports on undiscovered copper resources of other regions of the world are being prepared and will be followed by assessments of the global undiscovered resources of platinum-group minerals and potash

Targeted mitochondrial therapy using MitoQ shows equivalent renoprotection to angiotensin converting enzyme inhibition but no combined synergy in diabetes.

Mitochondrial dysfunction is a pathological mediator of diabetic kidney disease (DKD). Our objective was to test the mitochondrially targeted agent, MitoQ, alone and in combination with first line therapy for DKD. Intervention therapies (i) vehicle (D); (ii) MitoQ (DMitoQ;0.6 mg/kg/day); (iii) Ramipril (DRam;3 mg/kg/day) or (iv) combination (DCoAd) were administered to male diabetic db/db mice for 12 weeks (n = 11-13/group). Non-diabetic (C) db/m mice were followed concurrently. No therapy altered glycaemic control or body weight. By the study end, both monotherapies improved renal function, decreasing glomerular hyperfiltration and albuminuria. All therapies prevented tubulointerstitial collagen deposition, but glomerular mesangial expansion was unaffected. Renal cortical concentrations of ATP, ADP, AMP, cAMP, creatinine phosphate and ATP:AMP ratio were increased by diabetes and mostly decreased with therapy. A higher creatine phosphate:ATP ratio in diabetic kidney cortices, suggested a decrease in ATP consumption. Diabetes elevated glucose 6-phosphate, fructose 6-phosphate and oxidised (NAD+ and NADP+) and reduced (NADH) nicotinamide dinucleotides, which therapy decreased generally. Diabetes increased mitochondrial oxygen consumption (OCR) at complex II-IV. MitoQ further increased OCR but decreased ATP, suggesting mitochondrial uncoupling as its mechanism of action. MitoQ showed renoprotection equivalent to ramipril but no synergistic benefits of combining these agents were shown

Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans

© 2018 The Author(s) Imbalances in the oral microbial community have been associated with reduced cardiovascular and metabolic health. A possible mechanism linking the oral microbiota to health is the nitrate (NO3-)-nitrite (NO2-)-nitric oxide (NO) pathway, which relies on oral bacteria to reduce NO3- to NO2-. NO (generated from both NO2- and L-arginine) regulates vascular endothelial function and therefore blood pressure (BP). By sequencing bacterial 16S rRNA genes we examined the relationships between the oral microbiome and physiological indices of NO bioavailability and possible changes in these variables following 10 days of NO3- (12 mmol/d) and placebo supplementation in young (18–22 yrs) and old (70–79 yrs) normotensive humans (n = 18). NO3- supplementation altered the salivary microbiome compared to placebo by increasing the relative abundance of Proteobacteria (+225%) and decreasing the relative abundance of Bacteroidetes (−46%; P < 0.05). After NO3-supplementation the relative abundances of Rothia (+127%) and Neisseria (+351%) were greater, and Prevotella (−60%) and Veillonella (−65%) were lower than in the placebo condition (all P < 0.05). NO3- supplementation increased plasma concentration of NO2- and reduced systemic blood pressure in old (70–79 yrs), but not young (18–22 yrs), participants. High abundances of Rothia and Neisseria and low abundances of Prevotella and Veillonella were correlated with greater increases in plasma [NO2-] in response to NO3- supplementation. The current findings indicate that the oral microbiome is malleable to change with increased dietary intake of inorganic NO3-, and that diet-induced changes in the oral microbial community are related to indices of NO homeostasis and vascular health in vivo

Pan-American quantitative mineral resource assessment of copper, molybdenum, gold, and silver in undiscovered porphyry copper deposits in the Andes mountains, South America

Working together, the geological surveys of Argentina, Chile, Colombia, Peru, and the United States used the U. S. Geological Survey three-part mineral resource assessment methodology (Singer, 1993) to delineate the regional locations and make probabilistic estimates of the amounts of copper, molybdenum, silver, and gold in undiscovered porphyry copper deposits in the Andes. Quantitative information on the probable locations and amounts of undiscovered mineral resources of the world is important to exploration managers, land-use and environmental planners, economists, and policy makers

Trans-Resveratrol Oral Bioavailability in Humans Using LipiSperse™ Dispersion Technology

Resveratrol is a naturally produced compound that has been well researched for its potential health benefits. The primary hindrance towards resveratrol&rsquo;s therapeutic efficacy is its traditionally poor oral bioavailability. LipiSperse&reg; is a novel delivery system designed to increase the dispersion of lipophilic ingredients, like resveratrol, in aqueous environments. This single-dose, double-blind, randomized study compared the pharmacokinetics of a commercially available resveratrol with (Veri-Sperse&reg;) and without (Veri-te) the LipiSperse&reg; delivery complex. Healthy adults randomly received a single dose of either 150 Veri-te, 75 Veri-Sperse&reg;, or 150 mg Veri-Sperse&reg;. Venous blood samples were taken prior to dosing in a fasted state and at 0.5, 1, 2, 3, 4, 5, 6, 8 and 24 h post supplementation. Plasma trans-resveratrol conjugates were measured by liquid-chromatography tandem mass spectrometry (LC-MS/MS). The area under the curve (AUC) (0&ndash;24 h), maximum concentration (Cmax), and time of maximum concentration (Tmax) of plasma conjugates were calculated. The 150 mg dose of Veri-Sperse&reg; had a 2-fold increase in absorption (AUC) and a 3-fold increase in Cmax of trans-resveratrol conjugates compared to 150 mg Veri-te. There was no statistical difference between 75 Veri-Sperse and 150 mg Veri-te for AUC or Cmax of resveratrol conjugates. These findings provide support for the use of LipiSperse&reg; to improve absorption of resveratrol

The Effect of Levagen+ (Palmitoylethanolamide) Supplementation on Symptoms of Allergic Rhinitis—A Double-Blind Placebo-Controlled Trial

Background: Allergic rhinitis (AR) is an inflammatory, symptomatic disorder stimulated by antigen-specific immunoglobulin E inflammation in response to allergens. Current treatments include the use of corticosteroids and antihistamines to reduce inflammation by preventing histamine release. Palmitoylethanolamide (PEA) is reported to be an alternative treatment, shown to downregulate mast cell activation and increase the synthesis of endocannabinoid 2-Arachidonoylglycerol to reduce histamine and the symptoms of AR. Method: A double-blind, randomised, placebo-controlled clinical trial in which 108 participants presenting with seasonal AR were supplemented with either 350 mg of PEA (Levagen+) or a placebo daily for two weeks. Symptom scores were recorded using the reflective total nasal symptom score (rTNSS) twice a day (morning and evening) for the two weeks, and blood was taken at baseline and week 2. Results: 101 participants completed the study with no baseline group differences. No significant difference was seen between groups for allergy symptoms scores (rTNSS) throughout the 14 days of treatment. A sub-group analysis of participants scoring over four (mild-to-moderate) on the total rTNSS at baseline showed that Levagen+ significantly reduced scores compared to the placebo group. Only 36 participants had full sets of blood taken due to COVID-19. The pathology results showed a significant difference in change from baseline between groups. The Levagen+ group had a significant decrease from baseline in histamine, IL-4, IL-8, IL-10, and TNF-α. The placebo group only had a reduction in IL-4. Conclusion: The results of this study show that Levagen+ can alleviate AR symptoms, resulting in a reduction in histamine and inflammatory markers

Effectiveness of &ldquo;Moro&rdquo; Blood Orange Citrus sinensis Osbeck (Rutaceae) Standardized Extract on Weight Loss in Overweight but Otherwise Healthy Men and Women&mdash;A Randomized Double-Blind Placebo-Controlled Study

This study aimed to assess the efficacy of a blood orange Citrus sinensis standardized extract from &ldquo;Moro&rdquo; cultivar, on weight loss in overweight but otherwise healthy individuals. Anthocyanins and particularly cyanidin 3-glucoside, found in a large variety of fruits including Sicilian blood oranges, can help to counteract weight gain and to reduce body fat accumulation through the modulation of antioxidant, anti-inflammatory and metabolic pathways. In this randomized, double blind, placebo-controlled study, all participants (overweight adults aged 20&ndash;65 years old) were randomized to receive either Moro blood orange standardized extract or a placebo daily for 6-months. The primary outcome measure was change in body mass and body composition at the end of the study. After 6-months, body mass (4.2% vs. 2.2%, p = 0.015), body mass index (p = 0.019), hip (3.4 cm vs. 2.0 cm, p = 0.049) and waist (3.9 cm vs. 1.7 cm, p = 0.017) circumferences, fat mass (p = 0.012) and fat distribution (visceral and subcutaneous fat p = 0.018 and 0.006, respectively) were all significantly better in the extract supplemented group compared to the placebo (p &lt; 0.05). In addition, all safety markers of liver toxicity were within the normal range throughout the study for both analyzed groups. Concluding, the present study demonstrates that Moro blood orange standardized extract may be a safe and effective option for helping with weight loss when used in conjunction with diet and exercise