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Natural deep eutectic solvents (NaDES) represent a new generation of green, non-flammable solvents, useful as an efficient alternative to the well-known ionic liquids. They can be easily prepared and exhibit unexpected solubilizing power for lipophilic molecules, although those of a hydrophilic nature are mostly used. For their unique properties, they can be recommend for different cosmetic and pharmaceutical applications, ranging from sustainable extraction, obtaining ready-to-use ingredients, to the development of biocompatible drug delivery responsive systems. In the biomedical field, NaDES can be used as biopolymer modifiers, acting as delivery compounds also known as “therapeutic deep eutectic systems”, being able to solubilize and stabilize different chemical and galenical formulations. The aim of this review is to give an overview of the current knowledge regarding natural deep eutectic solvents specifically applied in the cosmetic and pharmaceutical fields. The work could help to disclose new opportunities and challenges for their implementation not only as green alternative solvents but also as potential useful pathways to deliver bioactive ingredients in innovative formulations.

The objective of this research was to optimize the natural deep eutectic solvent (NADES) extraction process from sour cherry kernels (Prunus cerasus L.). For polyphenol isolation, conventional solid–liquid extraction was employed using different concentrations of ethanol (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, and 96%), as well as the innovative NADES extraction technique. In the initial phase of the research, a screening of 10 different NADESs was conducted, while extraction was carried out under constant parameters (50 °C, 1:20 w/w, 60 min). NADES 4, composed of lactic acid and glucose in a molar ratio of 5:1, exhibited the highest efficiency in the polyphenol isolation. In the subsequent phase of the research, response surface methodology (RSM) was utilized to optimize the extraction process. Three independent variables, namely temperature, extraction time, and solid–liquid (S/L) ratio, were examined at three different levels. The extracted samples were analyzed for total phenol (TP) and antioxidant activity using the DPPH, ABTS, and FRAP assays. ANOVA and descriptive statistics (R2 and CV) were performed to fit the applied model. According to RSM, the optimal extraction conditions were determined as follows: temperature of 70 °C, extraction time of 161 min, and S/L ratio of 1:25 w/w.

In recent years, almost all extraction processes in the perfume, cosmetic, pharmaceutical, food ingredients, nutraceuticals, biofuel and fine chemical industries rely massively on solvents, the majority of which have petroleum origins. The intricate processing steps involved in the industrial extraction cycle makes it increasingly difficult to predict the overall environmental impact; despite the tremendous energy consumption and the substantial usage of solvents, often the yields are indicated in decimals. The ideal alternative solvents suitable for green extraction should have high solvency, high flash points with low toxicity and low environmental impacts, be easily biodegradable, obtained from renewable (non-petrochemical) resources at a reasonable price and should be easy to recycle without any deleterious effect to the environment. Finding the perfect solvent that meets all the aforementioned requirements is a challenging task, thus the decision for the optimum solvent will always be a compromise depending on the process, the plant and the target molecules. The objective of this comprehensive review is to furnish a vivid picture of current knowledge on alternative, green solvents used in laboratories and industries alike for the extraction of natural products focusing on original methods, innovation, protocols, and development of safe products.

Conventional extraction techniques are usually based on highly pollutant and/or flammable organic solvents. Therefore, alternative environmentally friendly extraction methods are of particular interest for the recovery of bioactive compounds for their application as food ingredients and/or nutraceuticals. Natural deep eutectic solvents (NADES) are a green and nontoxic attractive alternative to hydroalcoholic extraction. NADES media primarily depends on the intermolecular interactions (hydrogen bonding) among their components to form a eutectic mixture with a much lower final melting point than its individual components. Examples of natural deep eutectic NADES solvents include aqueous solutions (25%–50% water) of choline chloride, sugars, and polyols. This study aimed to investigate the application of two NADES, namely, betaine:triethylene glycol (Bet : TEG) and choline chloride:1,2-propanediol (Chol : Prop), as sustainable green solvents for the extraction of polyphenols from spent coffee ground (SCG), a by-product of coffee processing. In particular, the extraction yield and selectivity were evaluated and compared with conventional green extractions (hot water and a hydroalcoholic solution). In addition, the effect of NADES on the antioxidant and antimicrobial activity of the extracts was investigated. The main outcomes were as follows: (i) NADES were as effective as other conventional green solvents in the extraction of polyphenols with the added advantage of operating at milder temperature conditions, without flammable solvents and with sustainable and natural compounds; (ii) the antimicrobial activity of the NADES extracts was 10 times higher than that of the ethanolic and aqueous extracts. Given the low toxicity of NADES, they could be used as formulation aid for food ingredients.

PurposeStudy on curcumin dissolved in natural deep eutectic solvents (NADES) was aimed at exploiting their beneficial properties as drug carriers.MethodsThe concentration of dissolved curcumin in NADES was measured. Simulated gastrointestinal fluids were used to determine the concentration of curcumin and quantum chemistry computations were performed for clarifying the origin of curcumin solubility enhancement in NADES.ResultsNADES comprising choline chloride and glycerol had the highest potential for curcumin dissolution. This system was also successfully applied as an extraction medium for obtaining curcuminoids from natural sources, as well as an effective stabilizer preventing curcumin degradation from sunlight. The solubility of curcumin in simulated gastrointestinal fluids revealed that the significant increase of bioavailability takes place in the small intestinal fluid.ConclusionsSuspension of curcumin in NADES offers beneficial properties of this new liquid drug formulation starting from excreting from natural sources, through safe storage and ending on the final administration route. Therefore, there is a possibility of using a one-step process with this medium. The performed quantum chemistry computations clearly indicated the origin of the enhanced solubility of curcumin in NADES in the presence of intestinal fluids. Direct intermolecular contacts leading to hetero-molecular pairs with choline chloride and glycerol are responsible for elevating the bulk concentration of curcumin. Choline chloride plays a dominant role in the system and the complexes formed with curcumin are the most stable among all possible homo- and hetero-molecular pairs that can be found in NADES-curcumin systems.

The roots of the medicinal plant Aralia elata are rich in biologically active natural products, with triterpene saponins constituting one of their major groups. These metabolites can be efficiently extracted by methanol and ethanol. Due to their low toxicity, natural deep eutectic solvents (NADES) were recently proposed as promising alternative extractants for the isolation of natural products from medicinal plants. However, although NADES-based extraction protocols are becoming common in routine phytochemical work, their application in the isolation of triterpene saponins has not yet been addressed. Therefore, here, we address the potential of NADES in the extraction of triterpene saponins from the roots of A. elata. For this purpose, the previously reported recoveries of Araliacea triterpene saponins in extraction experiments with seven different acid-based NADES were addressed by a targeted LC-MS-based quantitative approach for, to the best of our knowledge, the first time. Thereby, 20 triterpene saponins were annotated by their exact mass and characteristic fragmentation patterns in the total root material, root bark and root core of A. elata by RP-UHPLC-ESI-QqTOF-MS, with 9 of them being identified in the roots of this plant for the first time. Triterpene saponins were successfully extracted from all tested NADES, with the highest efficiency (both in terms of the numbers and recoveries of individual analytes) achieved using a 1:1 mixture of choline chloride and malic acid, as well as a 1:3 mixture of choline chloride and lactic acid. Thereby, for 13 metabolites, NADES were more efficient extractants in comparison with water and ethanol. Our results indicate that new, efficient NADES-based extraction protocols, giving access to high recoveries of triterpene saponins, might be efficiently employed in laboratory practice. Thus, our data open the prospect of replacing alcohols with NADES in the extraction of A. elata roots.

DES are mixtures of two or more compounds, able to form liquids upon mixing, with lower freezing points when compared to the individual constituents (eutectic mixtures). This attitude is due to the specific hydrogen-bond interactions network between the components of the mixture. A notable characteristic of DES is the possibility to develop tailor-made mixtures by changing the components ratios or a limited water dilution, for special applications, making them attractive for pharmaceutical purposes. In this review, we focused our attention on application of ChCl-based DES in the synthesis of pharmaceutical compounds. In this context, these eutectic mixtures can be used as solvents, solvents/catalysts, or as chemical donors and we explored some representative examples in recent literature of such applications.

This study aimed to assess the nutritional value, phytochemical composition, and antioxidant activity of Kappaphycus alvarezii cultivated in Integrated Multi-Trophic Aquaculture (IMTA) systems. The parameters were nutritional components, phytochemical content, and aAntioxidant activity. K. alvarezii exhibited substantial nutritional value, with notable protein (15.3%) and carbohydrate (60.0%) content, along with essential minerals such as calcium and magnesium. Phytochemical analysis revealed significant levels of polyphenols (20.0 mg GAE/g), flavonoids (5.5 mg QE/g), and tannins (3.0 mg CE/g), as well as noteworthy saponin (1.2%) and alkaloid (0.9%) contents. Antioxidant assays demonstrated strong activities, with 80.2% DPPH and 70.5% ABTS radical scavenging, a FRAP value of 600 µmol Fe2+/g, and a total antioxidant capacity of 150 mg AA/g. The findings indicate that K. alvarezii from IMTA systems is a valuable source of nutrients and bioactive compounds with significant antioxidant properties.

Usual extraction processes for analyzing foods, supplements, and nutraceutical products involve massive amounts of organic solvents contributing to a negative impact on the environment and human health. In recent years, a new class of green solvents called natural deep eutectic solvents (NADES) have been considered a valid alternative to conventional solvents. Compared with conventional organic solvents, NADES have attracted considerable attention since they are sustainable, biodegradable, and non-toxic but also are easy to prepare, and have low production costs. Here we summarize the major aspects of NADEs such as the classification, preparation method physicochemical properties, and toxicity. Moreover, we provide an overview of novel extraction techniques using NADES as potential extractants of bioactive compounds from foods and food by-products, and application of NADEs in food analysis. This review aims to be useful for the further development of NAES and for broadening the knowledge of these new green solvents in order to increase their use for the extraction of bioactive compounds and in food analysis.

Wild thyme (Thymus serpyllum L.) herbal dust has been recognized as a potential underutilized resource for the recovery of antioxidants. The aim of this paper was to optimize natural deep eutectic solvent (NADES) extraction of polyphenols to obtain improved antioxidant activity of extracts determined by selected in vitro assays (DPPH, FRAP, and ABTS). Twenty different NADES systems were investigated in the first step of the screening of the extraction solvent and l-proline (Pro)–glycerine (Gly) based solvents provided the best results. Preliminary experiments organized by 25−1 fractional factorial design narrowed down the number of extraction factors from five (temperature, extraction time, NADES type, water content and L/S ratio) to three and determined their experimental domain for the final step. A face-centered central composite design with temperature (40–55–70 °C), extraction time (60–120–180 min) and L/S ratio (10–20–30 g NADES/g sample) was applied for influence analysis and process optimization. Multi-response optimization suggested a temperature of 65 °C, time of extraction of 180 min and L/S ratio of 28 g NADES/g DW as optimal extraction parameters. Experimental validation confirmed good agreement between experimental and predicted results in the extract obtained at optimal conditions and the interactions in the most suitable NADES (N16; Pro–Gly–H2O; 1:2:1) were confirmed by the 1H-NMR.