Natural Deep Eutectic Solvents for the Extraction of Bioactive Steroidal Saponins from Dioscoreae Nipponicae Rhizoma

In the present study, a simple and environmentally friendly extraction method based on natural deep eutectic solvents (NADESs) was established to extract four bioactive steroidal saponins from Dioscoreae Nipponicae Rhizoma (DNR). A total of twenty-one types of choline chloride, betaine, and L-proline based NADESs were tailored, and the NADES composed of 1:1 molar ratio of choline chloride and malonic acid showed the best extraction efficiency for the four steroidal saponins compared with other NADESs. Then, the extraction parameters for extraction of steroidal saponins by selected tailor-made NADES were optimized using response surface methodology and the optimal extraction conditions are extraction time, 23.5 min; liquid–solid ratio, 57.5 mL/g; and water content, 54%. The microstructure of the DNR powder before and after ultrasonic extraction by conventional solvents (water and methanol) and the selected NADES were observed using field emission scanning electron microscope. In addition, the four steroidal saponins were recovered from NADESs by D101 macroporous resin with a satisfactory recovery yield between 67.27% and 79.90%. The present research demonstrates that NADESs are a suitable green media for the extraction of the bioactive steroidal saponins from DNR, and have a great potential as possible alternatives to organic solvents for efficiently extracting bioactive compounds from natural products.     

Solubility and Stability of Some Pharmaceuticals in Natural Deep Eutectic Solvents-Based Formulations

Some medicines are poorly soluble in water. For tube feeding and parenteral administration, liquid formulations are required. The discovery of natural deep eutectic solvents (NADES) opened the way to potential applications for liquid drug formulations. NADES consists of a mixture of two or more simple natural products such as sugars, amino acids, organic acids, choline/betaine, and poly-alcohols in certain molar ratios. A series of NADES with a water content of 0–30% (w/w) was screened for the ability to solubilize (in a stable way) some poorly water-soluble pharmaceuticals at a concentration of 5 mg/mL. The results showed that NADES selectively dissolved the tested drugs. Some mixtures of choline-based NADES, acid-neutral or sugars-based NADES could dissolve chloral hydrate (dissociated in water), ranitidine·HCl (polymorphism), and methylphenidate (water insoluble), at a concentration of up to 250 mg/mL, the highest concentration tested. Whereas a mixture of lactic-acid–propyleneglycol could dissolve spironolacton and trimethoprim at a concentration up to 50 and 100 mg/mL, respectively. The results showed that NADES are promising solvents for formulation of poorly water-soluble medicines for the development of parenteral and tube feeding administration of non-water-soluble medicines. The chemical stability and bioavailability of these drug in NADES needs further studies.     

Development of natural deep eutectic solvent (NADES) based on choline chloride as a green solvent to extract phenolic compound from coffee husk waste

Natural deep eutectic solvent (NADES) has been successfully used as a green alternative for the extraction of polyphenolic compounds (phenolic) from coffee husk waste. The NADES was produced by combining b the choline chloride compound with glycerol, glucose, citric acid, and proline. Furthermore, it was characterized using FTIR with the appearance of a widening hydroxyl peak at a wave number of 3277–3364 cm^?1, indicating the presence of hydrogen bond interactions. The results showed that the best composition of NADES solvent was choline chloride and proline ratio of 1:1, providing an extraction yield of 5.88 mg GAE g^?1 with a polyphenol concentration in NADES of 294.02 mg/L. Optimum extraction conditions were carried out with the addition of 50 % water, extraction time of 30 min, and the ratio of sample weight to solvent volume (1:10), obtaining a yield of 6.16 mg GAE g^?1 and the concentration of polyphenols in NADES of 307.81 mg/L. The effect of temperature on the extraction process can increase the extract yield under conditions at 80 °C with a yield of 10.07 mg GAE g^?1 and a polyphenol concentration of 671.4 mg/L. The chlorogenic acid group of polyphenolic compounds was identified using HPLC at a retention time of 3.454 min with a concentration of 63 mg/L. Based on the results, NADES can be use as a green solvent for extracting active compounds from coffee husk waste. These extract can safely be applied to various medicinal and food products.     

Ternary choline chloride/caffeic acid/ethylene glycol deep eutectic solvent as both a monomer and template in a molecularly imprinted polymer

A molecularly imprinted polymer based on a ternary deep eutectic solvent comprised of choline chloride/caffeic acid/ethylene glycol was prepared. The caffeic acid in the ternary deep eutectic solvent was used as both a monomer and template. The molecularly imprinted polymer based on the ternary deep eutectic solvent was characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, field‐emission scanning electron microscopy, Brunauer–Emmett–Teller surface area analysis, atomic force microscopy, and elemental analysis. A series of molecularly imprinted polymers based on choline chloride/caffeic acid/ethylene glycol with different molar ratios was prepared and applied to the molecular recognition of polyphenols. A comparison of the recognition ability of molecularly imprinted polymers to polyphenols revealed that the choline chloride/caffeic acid/ethylene glycol (1:0.4:1, molar ratio) molecularly imprinted polymer had the best molecular recognition effect with 132 μg/g of protocatechuic acid, 104 μg/g of catechins, 80 μg/g of epicatechin, and 123 μg/g of caffeic acid in 6 h, as well as good molecular recognition ability for polyphenols from a Radix Asteris sample. These results show that the ternary deep eutectic solvent based molecularly imprinted polymer is a potential medium that can be applied to drug purification, drug delivery, and drug analysis.     

Choline Chloride–Lactic Acid-Based NADES As an Extraction Medium in a Response Surface Methodology-Optimized Method for the Extraction of Phenolic Compounds from Hazelnut Skin

Deep eutectic solvents (DESs) are promising green solvents for the extraction of compounds from food byproducts. Hazelnut (Corylus avellana L.) is one of the most commonly cultivated tree nuts worldwide. The skin represents one of the major byproducts of the hazelnut industry and accounts for 2.5% of the total hazelnut kernel weight. It is a rich source of phenolic compounds like flavan-3-ols, flavonols, dihydrochalcones, and phenolic acids. In this work, fifteen DESs based on choline chloride and betaine, with different compositions, were studied in order to test their phenolic compounds extraction efficiency through the determination of their total concentration via Folin–Ciocalteu assay. A qualitative analysis of extracted phenolic compounds was assessed by HPLC with UV and MS detection. Using the DES with the best extraction efficiency, a new ultrasound-assisted solid liquid extraction (UA-SLE) method was optimized though the response surface methodology (RSM), taking into account some extraction parameters. Efficient recovery of extracted phenolic compounds was achieved using a 35% water solution of choline chloride and lactic acid (molar ratio 1:2) as an extraction solvent, working at 80 °C and with a solid-to-solvent ratio of 1:25 gmL⁻¹. The optimized conditions made it possible to recover 39% more phenolic compounds compared to a classic organic solvent.     

Extraction of Anthocyanins from Borage (Echium amoenum) Flowers Using Choline Chloride and a Glycerol-Based,Deep Eutectic Solvent: Optimization,Antioxidant Activity,and In Vitro Bioavailability

Borage flower (Echium amoenum), an annual herb native to the Mediterranean region, is an excellent source of anthocyanins and is widely used in various forms due to its biological activities. In the present study, a choline chloride and glycerol (CHGLY)-based natural deep eutectic solvent (NADES) was applied in order to extract the anthocyanins from borage flowers. The traditional solvents, including water, methanol, and ethanol, were used to evaluate the efficiency of CHGLY. The results showed that CHGLY was highly efficient compared to the traditional solvents, providing the highest amounts of the total anthocyanin content (TAC), total phenolic content (TPC), total flavonoid content (TFC), individual anthocyanins, and antioxidant activity (DPPH radical scavenging (DPPH) and ferric-reducing antioxidant power (FRAP) assays). The most dominant anthocyanin found in studied borage was cyanidin-3-glucoside, followed by cyanin chloride, cyanidin-3-rutinoside, and pelargonidin-3-glucoside. The bioavailability % was 71.86 ± 0.47%, 77.29 ± 0.57%, 80.22 ± 0.65%, and 90.95 ± 1.01% for cyanidin-3-glucoside, cyanidin-3-rutinoside, by pelargonidin-3-glucoside and cyanin chloride, respectively. However, cyanidin-3-glucoside was the anthocyanin compound showing the highest stability (99.11 ± 1.66%) in the gastrointestinal environment. These results suggested that choline chloride and glycerol-based NADES is not only an efficient, eco-friendly solvent for the extraction of anthocyanins but can also be used to increase the bioavailability of anthocyanins.     

Vortex‐assisted natural deep eutectic solvent microextraction using response surface methodology optimization for determination of orthophosphate in water samples by molybdenum blue method

A new, rapid, and efficient microextraction technique named vortex‐assisted natural deep eutectic solvent microextraction has been developed for the preconcentration and determination of orthophosphate in real water samples. The method is based on the formation of the phosphomolybdenium blue complex followed by proposed microextraction procedure and subsequent spectrophotometric determination in a microcell. Screening study for the optimal composition of natural deep eutectic solvent was initially performed with different solvents, including choline chloride as hydrogen bond acceptor and different hydrogen bond donors. A ternary mixture of glucose‐choline chloride‐water was used as the most efficient extraction solvent. Response surface methodology based on the central composite design was used to optimize experimental parameters. Under optimal conditions, the calibration graph for orthophosphate determination was linear over the range of 2.0–80.0 µg/L (correlation coefficient of 0.9971) with a detection limit of 0.2 µg/L. The repeatability, reproducibility, and relative error values of the method were below 7%, indicating acceptable precision and accuracy. This approach, using natural deep eutectic solvent as an eco‐friendly solvent with high solubilization power and vortex mixing as an alternative energy source, represents a promising choice for a green separation and preconcentration methodology for determination of orthophosphate in real water samples.     

Extraction and determination of bioactive flavonoids from Abelmoschus manihot (Linn.) Medicus flowers using deep eutectic solvents coupled with high‐performance liquid chromatography

A highly efficient and ecofriendly extraction method using deep eutectic solvents was developed to extract bioactive flavonoids from Abelmoschus manihot (Linn.) Medicus flowers. First, a series of deep eutectic solvents using choline chloride as hydrogen bond acceptor with different hydrogen bond donors was successfully synthesized. Then, the types of deep eutectic solvents and the extraction conditions for bioactive flavonoids (hyperoside, isoquercitrin, and myricetin) were optimized based on the flavonoids extraction efficiencies. The optimized deep eutectic solvent for hyperoside and isoquercitrin extraction was composed of choline chloride and acetic acid with a molar ratio of 1:2. The optimized deep eutectic solvent for myricetin extraction was composed of one mole of choline chloride and two moles of methacrylic acid. The optimal extraction conditions were set as: solid to solvent ratio, 35:1 (mg/mL); extraction time, 30 min; extraction temperature, 30°C. Qualitative and quantitative analysis were performed using ultra high performance liquid chromatography with tandem mass spectrometry and high‐performance liquid chromatography. And the extraction efficiencies of hyperoside, isoquercitrin, and myricetin under optimal extraction conditions were calculated as 11.57, 5.64, and 1.11 mg/g, much higher than those extracted by traditional extraction solvents. Therefore, the prepared deep eutectic solvents can be selected as alternative solvent to extract bioactive flavonoids.     

Polyphenolic Compounds Extracted and Purified from Buddleja Globosa Hope (Buddlejaceae) Leaves Using Natural Deep Eutectic Solvents and Centrifugal Partition Chromatography

Chemical profiling of Buddleja globosa was performed by high-performance liquid chromatography coupled to electrospray ionization (HPLC-DAD-ESI-IT/MS) and quadrupole time-of-flight high-resolution mass spectrometry (HPLC-ESI-QTOF/MS). The identification of 17 main phenolic compounds in B. globosa leaf extracts was achieved. Along with caffeoyl glucoside isomers, caffeoylshikimic acid and several verbascoside derivatives (β-hydroxyverbascoside and β-hydroxyisoverbascoside) were identified. Among flavonoid compounds, the presence of 6-hydroxyluteolin-7-O-glucoside, quercetin-3-O-glucoside, luteolin 7-O-glucoside, apigenin 7-O-glucoside was confirmed. Campneoside I, forsythoside B, lipedoside A and forsythoside A were identified along with verbascoside, isoverbascoside, eukovoside and martynoside. The isolation of two bioactive phenolic compounds verbascoside and forsythoside B from Buddleja globosa (Buddlejaceae) was successfully achieved by centrifugal partition chromatography (CPC). Both compounds were obtained in one-step using optimized CPC methodology with the two-phase solvent system comprising ethyl acetate-n-butanol-ethanol-water (0.25:0.75:0.1:1, v/v). Additionally, eight Natural Deep Eutectic Solvents (NADESs) were tested for the extraction of polyphenols and compared with 80% methanol. The contents of verbascoside and luteolin 7-O-glucoside after extraction with 80% methanol were 26.165 and 3.206 mg/g, respectively. Among the NADESs tested in this study, proline- citric acid (1:1) and choline chloride-1, 2- propanediol (1:2) were the most promising solvents. With these NADES, extraction yields for verbascoside and luteolin 7-O-glucoside were 51.045 and 4.387 mg/g, respectively. Taken together, the results of this study confirm that CPC enabled the fast isolation of bioactive polyphenols from B. globosa. NADESs displayed higher extraction efficiency of phenolic and therefore could be used as an ecofriendly alternative to classic organic solvents.     

Novel Processes for the Extraction of Phenolic Compounds from Olive Pomace and Their Protection by Encapsulation

Olive pomace, the solid by-product derived from olive oil production consists of a high concentration of bioactive compounds with antioxidant activity, such as phenolic compounds, and their recovery by applying innovative techniques is a great opportunity and challenge for the olive oil industry. This study aimed to point out a new approach for the integrated valorization of olive pomace by extracting the phenolic compounds and protecting them by encapsulation or incorporation in nanoemulsions. Innovative assisted extraction methods were evaluated such as microwave (MAE), homogenization (HAE), ultrasound (UAE), and high hydrostatic pressure (HHPAE) using various solvent systems including ethanol, methanol, and natural deep eutectic solvents (NADESs). The best extraction efficiency of phenolic compounds was achieved by using NADES as extraction solvent and in particular the mixture choline chloride-caffeic acid (CCA) and choline chloride-lactic acid (CLA); by HAE at 60 °C/12,000 rpm and UAE at 60 °C, the total phenolic content (TPC) of extracts was 34.08 mg gallic acid (GA)/g dw and 20.14 mg GA/g dw for CCA, and by MAE at 60 °C and HHPAE at 600 MPa/10 min, the TPC was 29.57 mg GA/g dw and 25.96 mg GA/g dw for CLA. HAE proved to be the best method for the extraction of phenolic compounds from olive pomace. Microencapsulation and nanoemulsion formulations were also reviewed for the protection of the phenolic compounds extracted from olive pomace. Both encapsulation techniques exhibited satisfactory results in terms of encapsulation stability. Thus, they can be proposed as an excellent technique to incorporate phenolic compounds into food products in order to enhance both their antioxidative stability and nutritional value.     

Efficacy of Natural Deep Eutectic Solvents for Extraction of Hydrophilic and Lipophilic Compounds from Fucus vesiculosus

The impact of the composition of natural deep eutectic solvents (NADES) and extraction conditions on the simultaneous extraction of hydrophilic ascorbic acid (AA), phlorotannins (TPhC), and lipophilic fucoxanthin (FX) from Fucus vesiculosus was investigated for the first time. In biological tests, the NADES extracts showed the promising ability to scavenge DPPH radicals. A positive correlation was observed between DPPH scavenging activity and AA, TPhC, and FX contents. We calculate the synergistic effect of antioxidants extracted by NADES from F. vesiculosus based on the mixture effect (ME). The addition of 30% water to the NADES and the prolongation of sonication time from 20 min up to 60 min were favorable for the ME. The ME for extracts with the NADES was increased by two folds (ME > 2). In contrast, conventional extraction by maceration with steering at 60 °C does not lead to the synergistic effect (ME = 1). It is notable that the NADES provides high stability and preserves the antioxidant activity of the extracts from F. vesiculosus during storage.     

Fundamental studies on the feasibility of deep eutectic solvents for the selective partition of glaucarubinone present in the roots of Simarouba glauca

Several deep eutectic solvents prepared by the complexation of choline chloride as the hydrogen bond acceptor and hydrogen bond donors such as urea, thiourea, ethylene glycol, and glycerol were employed to partition glaucarubinone, an antimalarial compound present in roots of the plant, Simarouba glauca. Among all the solvents, the deep eutectic solvent consisting of the mixture of choline chloride and urea the most suitable to partition the antimalarial compound from the extract selectively. Analytical tools such as high‐performance liquid chromatography and electrospray ionization mass spectrometry were used for characterizations, and glaucarubinone extracted from the roots of the plant by conventional solvent extraction method was used as a reference for comparison. The hydrogen and noncovalent bonds formed between glaucarubinone and the deep eutectic solvents could be responsible for the selective partition of the drug molecule.     

Urea decomposition: Efficient synthesis of pyrroles using the deep eutectic solvent choline chloride/urea

A simple and efficient method is reported for the synthesis of pyrroles via condensation of a series of tricarbonyl compounds with ammonia, which was generated in situ from decomposition of the deep eutectic solvent choline chloride/urea.     

Green solvents from ionic liquids and deep eutectic solvents to natural deep eutectic solvents

Natural deep eutectic solvents (NADESs) are defined as mixtures of certain molar ratios of natural compounds such as sugars, organic acids, amino acids, and organic bases that are abundant in organisms. The melting points of these mixtures are considerably lower than those of their individual ingredients and far below ambient temperature. The first publications on the NADES concept in 2011 created a great expectation regarding their potential as green solvents that could replace conventional organic solvents in a wide range of applications. This was largely because many of the drawbacks of conventional synthetic ionic liquids (ILs) and deep eutectic solvents (DESs), particularly their toxicity and environmental hazards, could be solved using NADESs. Throughout the last 7 years, the interest in NADESs has increased enormously as reflected by the exponential growth of the number of related publications. The research on NADESs has rapidly expanded particularly into the evaluation of the feasibility of their application in diverse fields such as the extraction of (targeted) bioactive compounds from natural sources, as media for enzymatic or chemical reactions, preservatives of labile compounds, or as vehicles of non–water-soluble compounds for pharmaceutical purposes. Along with the exploration of these potential applications, there have been a large number of other studies related to their physicochemical features, the search for new NADESs, the research into the interactions between NADES components or with solutes, the recovery of solutes from NADES solutions, and the ways of circumventing inherent problems of NADESs such as their high viscosity and the consequent difficulties in handling them. This article contains a review of the applications of NADESs as extraction solvents, reaction media, and preservative, providing also a perspective of their future.     

Optimization extraction and purification of biological activity curcumin from Curcuma longa L by high‐performance counter‐current chromatography

The extraction condition of curcumin from Curcuma longa L was optimized through four factors and three levels orthogonal experiment based on the results of single factor tests. Under the optimal conditions: the concentration of ethanol  80%, extraction temperature 70°C, the ratio of liquid to material 20, and extraction time 3 h, a crude extract with the yield of curcumin 56.8 mg/g could be obtained. The isolation and purification of curcuminoids from the crude extract was performed on high performance counter current chromatography employing an optimized solvent system n‐hexane/ethyl acetate/methanol/water (2/3/3/1, v/v/v/v). From 97 mg crude sample (in which the purity of curmumin was 68.56%), 67 mg curmumin, 18 mg demethoxycurcumin, and 9.7 mg bisdemethoxycurcumin with a high‐performance liquid chromatography purity of 98.26, 97.39, and 98.67%, respectively, were obtained within 70 min. The antioxidant activities and cytotoxicity of purified curcumin was comparable to that of the commercial product, indicating that the biological activity of curcumin could be maintained by this method.     

Evaluation of green and efficient deep eutectic solvents as media for extracting alkaloids from lotus leaf

Deep eutectic solvents (DESs) were applied as eco-friendly solvents in this study for the extraction of alkaloids from lotus leaf, including O-nornuciferine, N-nornuciferine, nuciferine and roemerine. A series of hydrophilic and hydrophobic DESs with different hydrogen bond donors and a acceptors were synthesized and screened for a suitable DESs for extraction of alkaloids from lotus leaf. The study results showed that the hydrophilic DES with choline chloride and propanediol had the highest extraction yield. The main factors affecting the extraction efficiency—choline chloride–propanediol ratio, water content in deep eutectic solvents, solid–liquid ratio and extraction time—were investigated via a single-factor experiment. The optimized extraction conditions were 30% of water in choline chloride–propanediol (1:4) for heated extraction for 30 min and solid–liquid ratio 1:100 g/ml. Under optimum conditions, the extraction yields of O-nornuciferine, N-nornuciferine, nuciferine and roemerine were 0.069, 0.152, 0.334 and 0.041 g/100 g respectively, which were higher than those of methanol in acidified aqueous solution. This study suggests considerable potential for DESs as promising materials for the green and efficient extraction solvents for bioactive alkaloids from natural sources.     

HPTLC and FTIR Fingerprinting of Olive Leaves Extracts and ATR-FTIR Characterisation of Major Flavonoids and Polyphenolics

The aim of this study was to analyse the effect of spontaneous microbial maceration on the release and extraction of the flavonoids and phenolics from olive leaves. Bioprofiling based on thin-layer chromatography effect-directed detection followed by ATR-FTIR spectroscopy proved to be a reliable and convenient method for simultaneous comparison of the extracts. Results show that fermentation significantly enhances the extraction of phenolic compounds and flavonoids. The polyphenolic content was increased from 6.7 µg GAE (gallic acid equivalents) to 25.5 µg GAE, antioxidants from 10.3 µg GAE to 25.3 µg GAE, and flavonoid content from 42 µg RE (rutin equivalents) to 238 µg RE per 20 µL of extract. Increased antioxidant activity of fermented ethyl acetate extracts was attributed to the higher concentration of extracted flavonoids and phenolic terpenoids, while increased antioxidant activity in fermented ethanol extract was due to increased extraction of flavonoids as extraction of phenolic compounds was not improved. Lactic acid that is released during fermentation and glycine present in the olive leaves form a natural deep eutectic solvent (NADES) with significantly increased solubility for flavonoids.     

Using natural deep eutectic solvents for the extraction of metabolites in Byrsonima intermedia leaves

Natural deep eutectic solvents have been used as an alternative to organic solvents for the extraction of plants metabolites, allowing for the extraction of compounds of different polarities, while being inexpensive, non‐toxic, and easy to prepare. This work presents the comparison of the chromatographic profiles by high‐performance liquid chromatography with diode‐array detection obtained from Byrsonima intermedia (Malpighiaceae) using five choline chloride‐based natural deep eutectic solvents, in addition to the most used traditional extraction solvents, methanol/water 7:3 and ethanol/water 7:3 v/v. A reference extract was used to tentatively identify compounds by high‐performance liquid chromatography with tandem mass spectrometry. The water content appeared to be important for the extraction efficiency and the mixture choline chloride/glycerol was shown to be the best candidate for efficiently extracting this matrix when compared with the traditional extraction media in addition to being far greener as shown by the environmental analysis tool. Seven phenolic compounds (digalloyl quinic acid, proanthocyanidin dimer, galloylproanthocyanidin dimer, quercetin‐O‐hexoside, galloyl quercetin hexoside, quercetin‐O‐pentoside, and galloyl quercetin pentoside) were tentatively identified in all extracts. Moreover, the influence of these solvents on the antioxidant activity of the extracts was studied and the results for choline chloride/glycerol extracts were very similar to that of the traditional extraction solvents.     

Application of Deep Eutectic Solvents in the Synthesis of Substituted 2-Mercaptoquinazolin-4(3H)-Ones: A Comparison of Selected Green Chemistry Methods

In this study, deep eutectic solvents (DESs) were used as green and eco-friendly media for the synthesis of substituted 2-mercaptoquinazolin-4(3H)-ones from different anthranilic acids and aliphatic or aromatic isothiocyanates. A model reaction on anthranilic acid and phenyl isothiocyanate was performed in 20 choline chloride-based DESs at 80 °C to find the best solvent. Based on the product yield, choline chloride:urea (1:2) DES was found to be the most effective, while DESs acted both as solvents and catalysts. Desired compounds were prepared with moderate to good yields using stirring, microwave-assisted, and ultrasound-assisted synthesis. Significantly, higher yields were obtained with mixing and ultrasonication (16–76%), while microwave-induced synthesis showed lower effectiveness (13–49%). The specific contribution of this research is the use of DESs in combination with the above-mentioned green techniques for the synthesis of a wide range of derivatives. The structures of the synthesized compounds were confirmed by ¹H and ¹³C NMR spectroscopy.     

Green and enhanced extraction of coumarins from Cortex Fraxini by ultrasound‐assisted deep eutectic solvent extraction

Green and enhanced extraction of bioactive ingredients from medicinal plants has become a hot research field, and deep eutectic solvents have been considered as a novel kind of sustainable solvents in the extraction process. In this study, hydrogen bond acceptor (choline chloride, etc.) and hydrogen bond donor (l ‐malic acid, etc.) were used to prepare different kinds of deep eutectic solvents to extract coumarins from Cortex Fraxini. The extraction conditions, including the composition and moisture content of deep eutectic solvents, extraction time, and liquid‐solid ratio, were systematically optimized basing on the extraction yield of coumarins. To further investigate the extraction mechanism, Fourier transform infrared spectroscopy was performed, and the microstructures of Cortex Fraxini powders were observed before and after extraction using scanning electron microscope. Results showed that the novel ultrasound‐assisted extraction with conditions of deep eutectic solvent containing betaine/glycerin (1:3), aqueous solution (20%), solid‐liquid ratio (15 mg/mL), and extraction time (30 min) exhibited the best extraction yields for the four target coumarins and much better extraction efficiency than with conventional solvent extractions. This suggests that the new ultrasound‐assisted deep eutectic solvent extraction could be used as a green and high‐efficient approach for extraction of the main coumarins from Cortex Fraxini.