Enhanced in vivo absorption and biodistribution of curcumin loaded into emulsions with high medium-chain triglyceride content.

The health benefits of curcumin have been demonstrated by several clinical studies, but its low bioavailability compromises its functionality. In this regard, emulsions have proven to be effective encapsulation systems for curcumin. Nevertheless, emulsions with a high oil content (50%) may offer some advantages due to the large amount of compound they can incorporate. Therefore, the aim of this work was to study the pharmacokinetics and biodistribution of curcumin when carried in optimized emulsions containing 50% MCT oil and a plant-based emulsifier (soybean lecithin) at 2 h or 4 h post-oral administration to rats. The most stable emulsion was obtained using 50% of oil and a surfactant-oil-ratio 0.1, through a microfluidization process. After the oral administration of the systems (150 mg curcumin/kg body weight), curcumin glucuronide was the main compound present in plasma (AUC0-t = 1556.3 ng·h·ml-1), especially at 2-4 h post-administration. The total curcuminoid bioavailability was increased by 10.6-fold when rats were fed with the curcumin emulsion rather than with a control suspension. Moreover, rats fed with the emulsion showed the highest accumulation of free curcuminoids, which present the highest biological activity, in the liver (129 ng curcumin/g tissue) and brown adipose tissue (193 ng curcumin/g tissue). The obtained results are of great interest since the presence of curcumin in the brown adipose tissue has been shown to play a relevant role in the prevention of obesity and its related metabolic disorders.

Emulsion-Based Delivery Systems to Enhance the Functionality of Bioactive Compounds: Towards the Use of Ingredients from Natural, Sustainable Sources.

In recent years, the trend in the population towards consuming more natural and sustainable foods has increased significantly. This claim has led to the search for new sources of bioactive compounds and extraction methods that have less impact on the environment. Moreover, the formulation of systems to protect these compounds is also focusing on the use of ingredients of natural origin. This article reviews novel, natural alternative sources of bioactive compounds with a positive impact on sustainability. In addition, it also contains information on the most recent studies based on the use of natural (especially from plants) emulsifiers in the design of emulsion-based delivery systems to protect bioactive compounds. The properties of these natural-based emulsion-delivery systems, as well as their functionality, including in vitro and in vivo studies, are also discussed. This review provides relevant information on the latest advances in the development of emulsion delivery systems based on ingredients from sustainable natural sources.

Enhancing in vivo retinol bioavailability by incorporating ß-carotene from alga Dunaliella salina into nanoemulsions containing natural-based emulsifiers.

The use of microalgae as a source of bioactive compounds has gained interest since they present advantages vs higher plants. Among them, Dunaliella salina is one of the best sources of natural ß-carotene, which is the precursor of vitamin A. However, ß-carotene shows reduced oral bioavailability due to its chemical degradation and poor absorption. The work aimed to evaluate the influence of the emulsifier and oil concentration on the digestive stability of Dunaliella Salina-based nanoemulsions and study their influence on the digestibility and the ß-carotene bioaccessibility. In addition, the effect of the emulsifier nature on the absorption of ß-carotene and its conversion to retinol in vivo was also investigated. Results showed that the coalescence observed in soybean lecithin nanoemulsion during the gastrointestinal digestion reduced the digestibility and ß-carotene bioaccessibility. In contrast, whey protein nanoemulsion that showed aggregation in the gastric phase could be redispersed in the intestinal phase facilitating the digestibility and bioaccessibility of the compound. In vivo results confirmed that whey protein nanoemulsion increased the bioavailability of retinol to a higher extent (Cmax 685 ng/mL) than soybean lecithin nanoemulsion (Cmax 394 ng/mL), because of an enhanced ß-carotene absorption.

Effect of the Emulsifier Used in Dunaliella salina-Based Nanoemulsions Formulation on the ß-Carotene Absorption and Metabolism in Rats.

SCOPE: Microalgae such as Dunaliella salina are a potential sustainable source of natural ß-carotene due to their fast growth and high adaptability to environmental conditions. This work aims to evaluate the effect of the incorporation of ß-carotene from this alga into different emulsifier-type nanoemulsions (soybean lecithin [SBL], whey protein isolate [WPI], sodium caseinate [SDC]) on its absorption, metabolization, and biodistribution in rats. METHODS AND RESULTS: Nanoemulsions formulated with different emulsifiers at 8% concentration are obtained by five cycles of microfluidization at 130 mPa, then expose to an in vitro digestion or orally administer to rats. Feeding rats with nanoemulsions improves ß-carotene uptake compared to control suspension, especially using SDC and WPI as emulsifiers. A greater presence of ß-carotene and retinol in the intestine, plasma, and liver is observed, being the liver the tissue that shows the highest accumulation. This fact can be a consequence of the smaller droplets that protein-nanoemulsions present compared to that with SBL in the intestine of rats, which promote faster digestibility and higher ß-carotene bioaccessibility (35%-50% more) according to the in vitro observations. CONCLUSIONS: Nanoemulsions, especially those formulated with protein emulsifiers, are effective systems for increasing ß-carotene absorption, as well as retinol concentration in different rat tissues.

Physicochemical Properties and Bioaccessibility of Phenolic Compounds of Dietary Fibre Concentrates from Vegetable By-Products.

The agro-food industry generates a large volume of by-products, whose revaluation is essential for the circular economy. From these by-products, dietary fibre concentrates (DFCs) can be obtained. Therefore, the objective of this study was to characterise (a) the proximal composition by analysing soluble, insoluble and total Dietary Fibre (DF), (b) the physicochemical properties, and (c) the phenolic profile of artichoke, red pepper, carrot, and cucumber DFCs. In addition, the bioaccessibility of phenolic compounds was also evaluated after in vitro gastrointestinal and colonic digestions. The results showed that the DFCs had more than 30 g/100 g dw. The water holding and retention capacity of the DFCs ranges from 9.4 to 18.7 g of water/g. Artichoke DFC presented high concentration of phenolic compounds (8340.7 mg/kg) compared to the red pepper (304.4 mg/kg), carrot (217.4 mg/kg) and cucumber DFCs (195.7 mg/kg). During in vitro gastrointestinal digestion, soluble phenolic compounds were released from the food matrix, chlorogenic acid, the principal compound in artichoke and carrot DFCs, and hesperetin-7-rutinoside in red pepper cucumber DFCs. Total phenolic content decreased after in vitro colonic digestion hence the chemical transformation of the phenolic compounds by gut microbiota. Based on the results, DFCs could be good functional ingredients to develop DF-enriched food, reducing food waste.

Enhancing the Gastrointestinal Stability of Curcumin by Using Sodium Alginate-Based Nanoemulsions Containing Natural Emulsifiers.

Curcumin presents interesting biological activities but low chemical stability, so it has been incorporated into different emulsion-based systems in order to increase its bioaccessibility. Many strategies are being investigated to increase the stability of these systems. Among them, the use of polysaccharides has been seen to highly improve the emulsion stability but also to modulate their digestibility and the release of the encapsulated compounds. However, the effect of these polysaccharides on nanoemulsions depends on the presence of other components. Then, this work aimed to study the effect of alginate addition at different concentrations (0-1.5%) on the gastrointestinal fate and stability of curcumin-loaded nanoemulsions formulated using soybean lecithin or whey protein as emulsifiers. Results showed that, in the absence of polysaccharides, whey protein was more effective than lecithin in preventing curcumin degradation during digestion and its use also provided greater lipid digestibility and higher curcumin bioaccessibility. The addition of alginate, especially at ≥1%, greatly prevented curcumin degradation during digestion up to 23% and improved the stability of nanoemulsions over time. However, it reduced lipid digestibility and curcumin bioaccessibility. Our results provide relevant information on the use of alginate on different emulsifier-based nanoemulsions to act as carriers of curcumin.

Improving the In Vitro Bioaccessibility of ß-Carotene Using Pectin Added Nanoemulsions.

The intestinal absorption of lipophilic compounds such as ß-carotene has been reported to increase when they are incorporated in emulsion-based delivery systems. Moreover, the reduction of emulsions particle size and the addition of biopolymers in the systems seems to play an important role in the emulsion properties but also in their behavior under gastrointestinal conditions and the absorption of the encapsulated compound in the intestine. Hence, the present study aimed to evaluate the effect of pectin addition (0%, 1%, and 2%) on the physicochemical stability of oil-in-water nanoemulsions containing ß-carotene during 35 days at 4 °C, the oil digestibility and the compound bioaccessibility. The results showed that nanoemulsions presented greater stability and lower ß-carotene degradation over time in comparison with coarse emulsion, which was further reduced with the addition of pectin. Moreover, nanoemulsions presented a faster digestibility irrespective of the pectin concentration used and a higher ß-carotene bioaccessibility as the pectin concentration increased, being the maximum of ≈36% in nanoemulsion with 2% of pectin. These results highlight the potential of adding pectin to ß-carotene nanoemulsions to enhance their functionality by efficiently preventing the compound degradation and increasing the in vitro bioaccessibility.

Nanostructured Lipid-Based Delivery Systems as a Strategy to Increase Functionality of Bioactive Compounds.

Acquisition of a healthy lifestyle through diet has driven the food manufacturing industry to produce new food products with high nutritional quality. In this sense, consumption of bioactive compounds has been associated with a decreased risk of suffering chronic diseases. Nonetheless, due to their low solubility in aqueous matrices, high instability in food products during processing and preparation as well as poor bioavailability, the use of such compounds is sometimes limited. Recent advancements in encapsulation and protection of bioactive compounds has opened new possibilities for the development of novel food products. In this direction, the present review is attempting to describe encapsulation achievements, with special attention to nanostructured lipid-based delivery systems, i.e., nanoemulsions, multi-layer emulsions and liposomes. Functionality of bioactive compounds is directly associated with their bioavailability, which in turn is governed by several complex processes, including the passage through the gastrointestinal tract and transport to epithelial cells. Therefore, an overview of recent research on the properties of these nanostructured lipid-based delivery systems with a strong impact on the functionality of bioactive compounds will be also provided. Nanostructured lipid-based delivery systems might be used as a potential option to enhance the solubility, stability, absorption and, ultimately, functionality of bioactive compounds. Several studies have been performed in this line, modifying the composition of the nanostructures, such as the lipid-type or surfactants. Overall, influencing factors and strategies to improve the efficacy of encapsulated bioactive compounds within nanostructures have been successfully identified. This knowledge can be used to design effective targeted nanostructured lipid-based delivery systems for bioactive compounds. However, there is still a lack of information on food interactions, toxicity and long-term consumption of such nanostructures.

Impact of emulsifier nature and concentration on the stability of ß-carotene enriched nanoemulsions during in vitro digestion.

The presence of emulsifiers facilitates the formation of nanoemulsions and assists in their stabilisation. Moreover, behaviour of nanoemulsions along the gastrointestinal tract primarily depends on their composition, affecting the bioaccessibility of the encapsulated compound. The goal of this work was to study how ß-carotene-enriched nanoemulsions prepared with different emulsifiers (Tween 20, lecithin, sodium caseinate, sucrose palmitate) at various concentrations (2%-8%) would affect their stability (particle size and zeta potential) during an in vitro gastrointestinal tract (GIT) digestion. In addition, the lipid digestibility and ß-carotene's bioaccessibility of nanoemulsions was determined. Nanoemulsions stabilised with Tween 20, lecithin and sodium caseinate did not present any variation in particle size under stomach phase. After the intestinal GIT phase, all nanoemulsions experienced physical changes, i.e. either increase or decrease in their particle size depending on the nature and concentration of the emulsifier used. The zeta potential of all nanoemulsions was maintained negative throughout the GIT digestion; moreover, it was less negative after the stomach GIT phase (between -24.2 and -1.4 mV). Lecithin-stabilised nanoemulsions presented the highest number of free fatty acids when the emulsifier concentration increased from 2% to 8%. In this sense, nanoemulsions containing 8% of lecithin exhibited the highest ß-carotene bioaccessibility (23.5%), suggesting that lecithin can enhance lipid digestion and bioaccessibility of ß-carotene encapsulated within nanoemulsions. This study elucidates the importance of not only the emulsifier's nature but also the concentration used when designing nanoemulsions as delivery systems for lipophilic compounds.

Intake of grape procyanidins during gestation and lactation impairs reverse cholesterol transport and increases atherogenic risk indexes in adult offspring.

Cardiovascular disease (CVD) is one of the most prevalent noncommunicable diseases in humans. Different studies have identified dietary procyanidins as bioactive compounds with beneficial properties against CVD by improving lipid homeostasis, among other mechanisms. The aim of this work was to assess whether grape seed procyanidin consumption at a physiological dose during the perinatal period could influence the CVD risk of the offspring. Wistar rat dams were treated with a grape seed procyanidin extract (GSPE; 25mg/kg of body weight per day) or vehicle during gestation and lactation. The adult male offspring of GSPE-treated dams presented decreased high-density lipoprotein cholesterol (HDL-C) levels, increased total cholesterol-to-HDL-C ratios and an exacerbated fasting triglyceride-to-HDL-C ratios (atherogenic index of plasma) compared to the control group. Impaired reverse cholesterol transport (RCT) was evidenced by the accumulation of cholesterol in skeletal muscle and by decreased fecal excretion of cholesterol and bile acids, which was consistent with the observed mRNA down-regulation of the rate-limiting enzyme in the hepatic bile acid synthesis pathway Cyp7A1. Conversely, GSPE programming also resulted in up-regulated gene expression of different key components of the RCT process, such as hepatic Npc1, Abcg1, Abca1, Lxra, Srebp2, Lcat, Scarb1 and Pltp, and the repression of microRNA miR-33a expression, a key negative controller of hepatic RCT at the gene expression level. Our results show that maternal intake of grape procyanidins during the perinatal period impacts different components of the RCT process, resulting in increased CVD risk in the adult offspring.

Grape seed procyanidins administered at physiological doses to rats during pregnancy and lactation promote lipid oxidation and up-regulate AMPK in the muscle of male offspring in adulthood.

The aim of the present study was to test whether the administration of a grape seed procyanidin extract (GSPE) during pregnancy and lactation, at doses extrapolated to human consumption, programs male offspring toward improved metabolism in adulthood. For this purpose, female rats were fed a normal-fat diet (NFD) and treated with either GSPE (25 mg kg(-1) of body weight/day) or vehicle during gestation and lactation. The metabolic programming effects of GSPE were evaluated in the male offspring fed NFD from 30 to 170 days of life. No changes were observed in body weight, adiposity, circulating lipid profile and insulin sensitivity between the offspring of dams treated with GSPE (STD-GSPE group) and their counterparts (STD-veh). However, the STD-GSPE offspring had lower circulating levels of C-reactive protein and lower respiratory quotient values, shifting whole-body energy catabolism from carbohydrate to fat oxidation. Furthermore, the STD-GSPE animals also exhibited increased levels of total and phosphorylated AMP-activated protein kinase (AMPK) and an over-expression of the mRNA levels of key genes related to fatty acid uptake (Fatp1 and CD36) and ß-oxidation (pparα and had) in skeletal muscle. Our results indicate that GSPE programs healthy male offspring towards a better circulating inflammatory profile and greater lipid utilisation in adulthood. The metabolic programming effects of GSPE that are related to the enhancement of fatty acid oxidation in skeletal muscle seem to be mediated, at least in part, by AMPK. These findings could be of relevance in the prevention of pathologies associated to lifestyle and aging, such as obesity and insulin resistance.

Nanoemulsion-based delivery systems to improve functionality of lipophilic components.

The use of active lipophilic substances such as antimicrobials and health-related compounds in the food industry is still a challenge due to their poor water solubility and instability in food formulations. Nano-sized structures such as nanoemulsions of oil-in-water are regarded as useful tools with a great potential in the food sector to incorporate food ingredients. Reducing the size of the active compounds incorporated within a solution would increase the surface area per mass unit of nanoemulsions, thus enhancing solubility and stability in foods. In addition, the ability of the active lipids to penetrate across biological membranes is also enhanced, thus boosting their biological functionality. An overview of the most significant studies reporting data about the potential benefits of active lipid nanoemulsions over conventional emulsions is presented.

Impact of high-intensity pulsed electric fields on carotenoids profile of tomato juice made of moderate-intensity pulsed electric field-treated tomatoes.

The effect of pulsed electric fields (PEF) on the carotenoid content of tomato juices was studied. First, moderate-intensity PEF (MIPEF) was applied to raw tomatoes. Afterwards, MIPEF-treated and untreated tomatoes were immediately refrigerated at 4 °C for 24 h and then, they were separately ground to produce tomato juices. Juices were treated by heat treatments or by high-intensity PEF (HIPEF) and stored under refrigeration for 56 days. MIPEF treatment of tomatoes increased the content of carotenoid compounds in tomato juices. An enhancement of 63-65% in 15-cis-lycopene was observed in juices prepared with MIPEF-treated tomatoes. A slight increase in cis-lycopene isomers was observed over time, whereas other carotenoids slightly decreased. However, HIPEF treated tomato juices maintained higher carotenoid content (10-20%) through the storage time than thermally and untreated juices. The combination of MIPEF and HIPEF treatments could be used not only to produce tomato juices with high carotenoid content but also, to maintain higher the carotenoid content during storage time.

Distribution of grape seed flavanols and their metabolites in pregnant rats and their fetuses.

SCOPE: Polyphenols have been demonstrated to provide health benefits affecting cellular and physiological processes. This study aims to evaluate the bioavailability and distribution of grape seed flavanol compounds during pregnancy and whether fetuses could be exposed to these compounds. METHODS AND RESULTS: The distribution of flavanols and their metabolites in rat plasma, liver, white adipose tissue, brain, amniotic fluid, placenta, and fetuses after 1 and 2 h of an acute intake of a grape seed proanthocyanidin extract was examined by LC-ESI-TOF/MS. Flavanols and their metabolites were widely distributed in both pregnant and nonpregnant rat plasma and tissues. In liver, the conjugated forms of flavanols were less available in pregnant than nonpregnant rats. Flavanol metabolites were abundant in maternal placenta but detected at low levels in fetuses and amniotic fluid. CONCLUSION: Flavanol metabolization appears to be less active in the liver during pregnancy. Moreover, data indicated that transport across the placenta is not efficient and for flavanols and their metabolites, the placenta seems to act as a barrier. However, these compounds target the fetus and are excreted in the amniotic fluid.

Metabolite profiling of phenolic and carotenoid contents in tomatoes after moderate-intensity pulsed electric field treatments.

A metabolite profiling approach was used to study the effect of moderate-intensity pulsed electric field (MIPEF) treatments on the individual polyphenol and carotenoid contents of tomato fruit after refrigeration at 4°C for 24h. The MIPEF processing variables studied were electric field strength (from 0.4 to 2.0kV/cm) and number of pulses (from 5 to 30). Twenty four hours after MIPEF treatments, an increase was observed in hydroxycinnamic acids and flavanones, whereas flavonols, coumaric and ferulic acid-O-glucoside were not affected. Major changes were also observed for carotenoids, except for the 5-cis-lycopene isomer, which remain unchanged after 24h of MIPEF treatments. MIPEF treatments, conducted at 1.2kV/cm and 30 pulses, led to the greatest increases in chlorogenic (152%), caffeic acid-O-glucoside (170%) and caffeic (140%) acids. On the other hand, treatments at 1.2kV/cm and 5 pulses led to maximum increases of α-carotene, 9- and 13-cis-lycopene, which increased by 93%, 94% and 140%, respectively. Therefore, MIPEF could stimulate synthesis of secondary metabolites and contribute to production of tomatoes with high individual polyphenol and carotenoid contents.

Changes in the polyphenol profile of tomato juices processed by pulsed electric fields.

The effect of pulsed electric fields on the polyphenol profile of tomato juices was studied. First, tomatoes were subjected to moderate-intensity pulsed electric fields (MIPEFs) and then were immediately refrigerated at 4 °C for 24 h. Treated and untreated juices were then subjected to high-intensity pulsed electric fields (HIPEFs) or thermal treatment (90 °C for 60 s). In comparison to references, tomatoes subjected to MIPEF treatments led to juices with a higher content of polyphenol compounds. A slight decrease in polyphenol compounds was observed over time in thermal- and HIPEF-treated juices, with the exception of caffeic acid. However, HIPEF-processed tomato juices had a higher content of polyphenol compounds (ferulic acid, caffeic-O-glucoside acid, p-coumaric acid, chlorogenic acid, rutin, and naringenin) just after processing and through storage than those thermally treated. Therefore, the combination of MIPEFs and HIPEFs could be proposed as a strategy for producing tomato juices with a higher content of phenolic compounds.

Effects of pulsed electric fields on the bioactive compound content and antioxidant capacity of tomato fruit.

The effect of moderate intensity pulsed electric fields (MIPEF) on the bioactive compounds (total polyphenol, lycopene, and vitamin C content) as well as on the antioxidant capacity of tomato fruit was studied. The MIPEF treatment conditions were optimized to obtain tomato fruit with a high content of bioactive compounds. Tomato fruits were subjected to different electric field strengths (from 0.4 to 2.0 kV/cm) and number of pulses (from 5 to 30) and then immediately refrigerated at 4 °C for 24 h. A concentration of bioactive compounds higher than that of untreated tomatoes was obtained in MIPEF-treated tomatoes. A 44% increase in total polyphenol content was achieved under 30 pulses at 1.2 kV/cm. The hydrophilic antioxidant capacity was also enhanced by 44% applying 18 pulses at 1.2 kV/cm, and the lipophilic antioxidant capacity was increased by 37% under 5 pulses at 1.2 kV/cm. The maximum overall level of bioactive compounds and antioxidant capacity in the treated tomatoes was obtained under 16 pulses at 1 kV/cm. Therefore, MIPEF treatments could be considered an effective method to enhance the bioactive compound content and antioxidant potential of tomatoes.

Effect of high-oxygen atmospheres on the antioxidant potential of fresh-cut tomatoes.

The effect of different initial in-package O2 and CO2 concentrations (2.5 kPa of O2 + 5 kPa of CO2, 10 kPa of O2 + 5 kPa of CO2, and 21, 60, and 80 kPa of O2) on the antioxidant potential of fresh-cut tomatoes was investigated. Changes in individual phenolic compounds, individual carotenoids, vitamin C, and antioxidant capacity as well as in O2, CO2, and ethylene headspace concentrations inside packages were assessed for 21 days at 4 degrees C. High-oxygen and passive atmospheres induced higher production of carotenoids and phenolic compounds. The degradation of the initial content of vitamin C was highly promoted by the presence of oxygen. Lower hydrophilic antioxidant capacity (DPPH assay) was obtained in tomato slices stored under 80 kPa of O2, whereas the antioxidant capacity of the lipophilic fraction was enhanced with oxygen availability inside headspace packages. Therefore, 2.5 kPa of O2 + 5 kPa of CO2 atmospheres not only reduced the formation of carotenoids but also maintained vitamin C in fresh-cut tomatoes.

Antioxidant content of fresh-cut pears stored in high-O2 active packages compared with conventional low-o2 active and passive modified atmosphere packaging.

The antioxidant content of fresh-cut 'Flor de Invierno' ( Pyrus communis L.) pears dipped into a 0.75% w/v N-acetylcysteine + 0.75% w/v glutathione solution and packaged under 70 kPa of O2 atmospheres (HOA) was evaluated as an alternative to actively modified low-O2 atmosphere (LOA) and passively modified atmospheres (PA). Changes in color, vitamin C, individual phenolic compounds, and antioxidant activity of fresh-cut pears as well as in O2, CO2, and ethylene headspace concentrations inside the packages were assessed for 14 days at 4 degrees C. Not only did the use of antioxidants prevent browning and reduce ethylene production of fresh-cut pears, but also their application under LOA best maintained vitamin C, chlorogenic acid, and antioxidant capacity compared with HOA. The results show that the use of glutathione and N-acetylcysteine enhanced the formation of phenylpropanoids in fresh-cut pears stored under LOA.