Application of deep eutectic solvents on extraction of flavonoids.

Deep eutectic solvents (DESs), as a new type of eco-friendly solvent, have attracted increasing attention on the extraction and separation of flavonoid compounds from various samples, owing to their excellent properties such as biodegradability and ease of handling with very low toxicity. This article provides a status review of the applications of DESs in the extraction of flavonoids, including the introduction of flavonoid compounds, the properties and superiority of DESs, and extraction methods (ultrasonic-assisted extraction, heating reflux extraction, matrix solid-phase dispersion, and solid-phase extraction). Finally, prospects and challenges in the application of DESs on extraction and separation are extensively elucidated and critically reviewed.

Vasorelaxant Activity of (2S)-Sakuranetin and Other Flavonoids Isolated from the Green Propolis of the Caatinga Mimosa tenuiflora.

Some in vitro and in vivo evidence is consistent with the cardiovascular beneficial activity of propolis. As the single actors responsible for this effect have never been identified, an in-depth investigation of flavonoids isolated from the green propolis of the Caatinga Mimosa tenuiflora was performed and their mechanism of action was described. A comprehensive electrophysiology, functional, and molecular docking approach was applied. Most flavanones and flavones were effective CaV1.2 channel blockers with a potency order of (2S)-sakuranetin > eriodictyol-7,3'-methyl ether > quercetin 3-methyl ether > 5,4'-dihydroxy-6,7-dimethoxyflavanone > santin > axillarin > penduletin > kumatakenin, ermanin and viscosine being weak or modest stimulators. Except for eriodictyol 5-O-methyl ether, all the flavonoids were also effective spasmolytic agents of vascular rings, kumatakenin and viscosine also showing an endothelium-dependent activity. (2S)-Sakuranetin also stimulated KCa1.1 channels both in single myocytes and vascular rings. In silico analysis provided interesting insights into the mode of action of (2S)-sakuranetin within both CaV1.2 and KCa1.1 channels. The green propolis of the Caatinga Mimosa tenuiflora is a valuable source of multi-target vasoactive flavonoids: this evidence reinforces its nutraceutical value in the cardiovascular disease prevention arena.

Improvement of Alginate Extraction from Brown Seaweed (Laminaria digitata L.) and Valorization of Its Remaining Ethanolic Fraction.

This study aimed to improve the conventional procedure of alginate isolation from the brown seaweed (Laminaria digitata L.) biomass and investigate the possibility of further valorization of the ethanolic fraction representing the byproduct after the degreasing and depigmentation of biomass. The acid treatment of biomass supported by ultrasound was modeled and optimized regarding the alginate yield using a response surface methodology based on the Box-Behnken design. A treatment time of 30 min, a liquid-to-solid ratio of 30 mL/g, and a treatment temperature of 47 °C were proposed as optimal conditions under which the alginate yield related to the mass of dry biomass was 30.9%. The use of ultrasonic radiation significantly reduced the time required for the acid treatment of biomass by about 4 to 24 times compared to other available conventional procedures. The isolated alginate had an M/G ratio of 1.08, which indicates a greater presence of M-blocks in its structure and the possibility of forming a soft and elastic hydrogel with its use. The chemical composition of the ethanolic fraction including total antioxidant content (293 mg gallic acid equivalent/g dry weight), total flavonoid content (14.9 mg rutin equivalent/g dry weight), contents of macroelements (the highest content of sodium, 106.59 mg/g dry weight), and microelement content (the highest content of boron, 198.84 mg/g dry weight) was determined, and the identification of bioactive compounds was carried out. The results of ultra high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry analysis confirmed the presence of 48 compounds, of which 41 compounds were identified as sugar alcohol, phenolic compounds, and lipids. According to the 2,2-diphenyl-1-picrylhydrazyl assay, the radical scavenging activity of the ethanolic fraction (the half-maximal inhibitory concentration of 42.84 ± 0.81 µg/mL) indicated its strong activity, which was almost the same as in the case of the positive control, synthetic antioxidant butylhydroxytoluene (the half-maximal inhibitory concentration of 36.61 ± 0.79 µg/mL). Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis, and Bacillus cereus) were more sensitive to the ethanolic fraction compared to Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, and Shigella sonnei). The obtained results indicated the possibility of the further use of the ethanolic fraction as a fertilizer for plant growth in different species and antifouling agents, applicable in aquaculture.

Functional genomics and metabolomics advance the ethnobotany of the Samoan traditional medicine "matalafi".

The leaf homogenate of Psychotria insularum is widely used in Samoan traditional medicine to treat inflammation associated with fever, body aches, swellings, wounds, elephantiasis, incontinence, skin infections, vomiting, respiratory infections, and abdominal distress. However, the bioactive components and underlying mechanisms of action are unknown. We used chemical genomic analyses in the model organism Saccharomyces cerevisiae (baker's yeast) to identify and characterize an iron homeostasis mechanism of action in the traditional medicine as an unfractionated entity to emulate its traditional use. Bioactivity-guided fractionation of the homogenate identified two flavonol glycosides, rutin and nicotiflorin, each binding iron in an ion-dependent molecular networking metabolomics analysis. Translating results to mammalian immune cells and traditional application, the iron chelator activity of the P. insularum homogenate or rutin decreased proinflammatory and enhanced anti-inflammatory cytokine responses in immune cells. Together, the synergistic power of combining traditional knowledge with chemical genomics, metabolomics, and bioassay-guided fractionation provided molecular insight into a relatively understudied Samoan traditional medicine and developed methodology to advance ethnobotany.

The First Comprehensive Chemical Profiling of Vachellia gummifera (Willd.) Kyal. & Boatwr., a Plant with Medicinal Value.

Vachellia gummifera (Willd.) Kyal. & Boatwr. is a medicinal plant endemic to Morocco that has no documented studies on its chemical composition. In this study, the chemical composition of the water/methanol (4 : 1) extracts of air-dried leaf and stem samples of Moroccan V. gummifera was determined using UHPLC-MS and NMR. In total, over 100 metabolites were identified in our study. Pinitol was the major compound in both the leaf and stem extracts, being significantly more abundant in the former. Asparagine and 3-hydroxyheteroendrin were the second most abundant compounds in the stem and leaf extracts, respectively, though both compounds were present in each tissue. The other compounds included flavonoids based on quercetin, and phenolic derivatives. Eucomic acid, only identified in the stems and was the major aromatic compound distinguishing the leaf and stem profiles. Quercetin 3-O-(6''-O-malonyl)-ß-D-glucopyranoside was identified as the major flavonoid in the leaves but was also present in the stems. Other malonylated derivatives that were all flavonol glycosides based on myricetin, kaempferol, and isorhamnetin in addition to quercetin were also identified. This is the first report of eucomic acid and malonylated compounds in Vachellia species. This report provides valuable insights into the chemotaxonomic significance of the Vachellia genus.

Chemical Profile and Biological Potential of Scaptotrigona Bee Products (Hymenoptera, Apidae, Meliponini): An Review.

Stingless bees belong to the Meliponini tribe and are widely distributed in the tropics and subtropics, where they perform important ecological services. Among the best distributed groups of stingless bees is the genus Scaptotrigona, which includes 22 species distributed throughout the neotropical region, including the area from Mexico to Argentina. Bees of this genus are responsible for the production of products such as honey, propolis, geopropolis and fermented pollen ("saburá"). This review aimed to provide an overview of the chemical composition and biological activities associated with derived products from stingless bees of the genus Scaptotrigona. The bibliographic review was carried out through searches in the Scopus, Web of Science, ScienceDirect and PubMed databases, including publications from 2003 to January 2023. The study of the chemodiversity of products derived from Scaptotrigona demonstrated the mainly presence of flavonoids, phenolic acids, terpenoids and alkaloids. It was also demonstrated that products derived from bees of the genus Scaptotrigona exhibit a wide range of biological effects, such as antibacterial, antioxidant, anti-inflammatory and antifungal activities, among other bioactivities. This review provides an overview of phytochemical and pharmacological investigations of the genus Scaptotrigona. However, it is essential to clarify the toxicity and food safety of these products.

Flavonoids From the Aerial Parts of Sophora tonkinensis and Their Potential Anti-Inflammatory Activities.

Four undescribed prenylated flavonoids, sophoratones A-D (1-4), and 17 known flavonoids, were obtained from the aerial parts of Sophora tonkinensis. Their structures with absolute configurations were elucidated by detailed interpretation of NMR spectroscopy, mass spectrometry, and ECD calculations. Meanwhile, the ability of these compounds to inhibit the release of nitric oxide (NO) by a lipopolysaccharide induced mouse in RAW 264.7 cells was assayed. The results indicated that some compounds exhibited clear inhibitory effects, with IC50 ranging from 19.91±1.08 to 35.72±2.92 µM. These results suggest that prenylated flavonoids from the aerial parts of S. tonkinensis could potentially be used as a latent source of anti-inflammatory agents.

Chemical Constituents of the Fruits of Cornus Officinalis and Evaluation of their Neuroprotective Activity.

The phytochemical investigation of the fruits of Cornus officinalis yielded a new phenolic acid derivative, neophenolic acid A (1), and a novel flavonoid glycoside, (2R)-naringenin-7-O-ß-(6''-galloyl-glucopyranoside) (2 a), along with six known flavonoid glycosides (2 b-7). Their structures were determined by 1D, 2D NMR and HRESIMS data. The absolute configuration of 1 was established by ECD analysis. Compounds 1- 7 were evaluated for their neuroprotective activities against corticosterone (CORT)-induced injury in PC-12 cells. Compounds 1, 2 a, 2 b, 5, and 6 exhibited neuroprotective activities against CORT-induced neurotoxicity in PC-12 cells. The underlying mechanism study suggested that compounds 1, 2 a, 2 b, 5, and 6 were able to attenuate CORT-induced apoptosis and damage, increase the levels of MMP and decrease Ca2+ inward flow in PC-12 cells.

Flavonoids and Triterpenoids Isolated From the Ethyl Acetate Extract of M. quadrangulata Leaves.

The new flavonoid (-)-4'-O-methylepicatechin 5-O-ß-D-glucopyranoside (1), along with four known triterpenes (2-5), a steroid (6), and a flavonoid (7) were isolated from the ethyl acetate extract of Maytenus quadrangulata leaves. The chemical structures of the isolated compounds were determined through analysis of 1D NMR (1H and 13C) spectroscopic data, in addition to 2D NMR and spectrometric (MS) data for compound 1. This is the first report of the isolation of daucosterol (6) and (-)-4'-O-methylepigallocatechin (7) from this species. Compounds 1 and 7 were evaluated against the bacteria Staphylococcus aureus and Klebsiella pneumoniae, but neither exhibited activity even at the highest concentration tested.

Exploring the Pharmacognostical and Phytochemical Profiles of Aqueous Extracts of Kalanchoe.

The use of plants for medicinal purposes has a long history, however it is desirable a continuous evaluation seeking for complementary scientific evidences for their safe application. Species within the Kalanchoe genus are often referred to as "miracle leaf" due to their remarkable healing properties. Traditionally, these plants have been used to treat infections, inflammation, and cancer. Despite their widespread use, the identification of their active components remains incomplete. This study aimed to differentiate K. crenata (KC), K. marmorata (KM), and K. pinnata (KP) by conducting detailed histochemical and phytochemical analyses, and to assess their antioxidant capabilities. The investigation revealed significant differences between the species, highlighting the variability in phenolic (PC) and flavonoid contents (FC) and their distinct antioxidant effects. The KM demonstrated the greatest results (PC: 59.26±1.53 mgEqGA/g; FC: 12.63±0.91 mgEqCQ/g; DPPH⋅ (IC50): 110.66 ug/mL; ABTS⋅+ (IC50): 26.81 ug/mL; ORAC: 9.65±0.75 mmolTE) when compared to KC and KP. These findings underscore a new reference for research within the Kalanchoe genus.

Chemical Composition of Extracts and Fractions from Miconia Ibaguensis (Melastomataceae) Leaves and Evaluation of Biological Activities.

The study aimed to assess the chemical composition of Miconia ibaguensis leaves extracts and fractions obtained from the ethanolic extract (EE), along with evaluating their antifungal, antibacterial, antidiabetic, and antioxidant activities. The ethyl acetate fraction (EAF) exhibited potent antifungal activity against Candida spp (1.95-3.90 µg mL-1) and potent antioxidant activity in the DPPH (1.74±0.07 µg mL-1), FRAP (654.01±42.09 µmol ETrolox/gsample), and ORAC (3698.88±37.28 µmol ETrolox/gsample) methods. The EE displayed inhibition against the α-amylase enzyme (8.42±0.05 µg mL-1). Flavonoids, hydrolysable tannins, triterpenoids, and phenolic acids, identified in the EE and fractions via (-)-HPLC-ESI-MS/MS analysis, were found to contribute to the species' biological activity potentially. These findings suggest promising avenues for further research and potential applications in pharmacology and natural products, offering new possibilities in the fight against global health issues.

Flavonoid Compounds in Hippophae rhamnoides L. Protect Endothelial Cells from Oxidative Damage Through the PI3K/AKT-eNOS Pathway.

Sea buckthorn, a traditional medicinal plant, has been used for several years in China for the prevention and treatment of various diseases, a practice closely associated with its significant antioxidant activity. The aim of this study was to investigate the protective effects of sea buckthorn flavonoids on vascular endothelial cells in an oxidative stress environment. We isolated and extracted active compounds from sea buckthorn and investigated their impact on endothelial nitric oxide synthase (eNOS) activity through the PI3K/AKT-eNOS signaling pathway through a combination of network pharmacology and cellular experiments, elucidating the regulatory effects of these compounds on endothelial cell functions. Three flavonoids, named Fr.4-2-1, Fr.4-2-2 and Fr.4-2-3, were obtained from sea buckthorn. The results of network pharmacology indicated that they might exert their effects by regulating the PI3K-AKT signaling pathway. In vitro results showed that all three flavonoids were effective in alleviating the degree of oxidative stress in cells, among which Fr.4-2-1 exerted its antioxidant effects by modulating the PI3K/AKT-eNOS pathway. Flavonoids in sea buckthorn can effectively inhibit oxidative stress-induced cellular damage, preserving the integrity and functionality of endothelial cells, which is crucial for maintaining vascular health and function.

Microwave and ultrasound extraction of antioxidant phenolic compounds from Lantana camara Linn. leaves: Optimization, comparative study, and FT-Orbitrap MS analysis.

INTRODUCTION: The species Lantana camara is used in folk medicine. The biological activities of this medicinal plant are attributable to the presence of various derivatives of triterpenoids and phenolic compounds present in its preparations, indicating excellent economic potential. OBJECTIVE: In this study, the operational conditions of ultrasound-assisted extraction (UAE) and microwave-assisted extraction (MAE) were optimized using Box-Behnken design to improve the total phenolic content (TPC) recovered in hydroethanolic extracts of L. camara leaves. MATERIAL AND METHODS: The TPC, total flavonoid content (TFC), and antioxidant activities of the hydroalcoholic extracts of L. camara, prepared by UAE and MAE under the optimized extraction conditions, were compared with those of the extracts obtained by conventional extraction methods. RESULTS: Under the optimal conditions, the extracts obtained by UAE (35% ethanol, 25 min, and a solvent-to-solid ratio of 60:1 mL/g) and by MAE (53% ethanol, 15 min, and 300 W) provided high yields of 32.50% and 38.61% and TPC values of 102.89 and 109.83 mg GAE/g DW, respectively. The MAE extract showed the best results with respect to TPC, TFC, and antioxidant activities, followed by extracts obtained by UAE, Soxhlet extraction, decoction, maceration, and infusion, in that order. CONCLUSION: The results obtained indicate that L. camara may be used as an important source of antioxidant phenolic compounds to obtain products with high biological and economic potential, especially when the extraction process is performed under appropriate conditions using MAE and/or UAE, employing environmentally friendly solvents such as water and ethanol.

Bioactive neolignan, iridoid and flavonoid glycosides from the leaves of Vaccinium bracteatum.

Two neolignan glycosides including a new one (1), along with seven iridoid glycosides (3 - 9) and nine flavonoid glycosides (10 - 18), were isolated from the leaves of Vaccinium bracteatum. Their structures were established mainly on the basis of 1D/2D NMR and ESIMS analyses, as well as comparison to known compounds in the literature. The structure of 1 with absolute stereochemistry was also confirmed by chemical degradation and ECD calculation. Selective compounds showed antiradical activity against ABTS and/or DPPH. Moreover, several isolates also suppressed the production of ROS in RAW264.7 cells and exerted neuroprotective effect toward PC12 cells.

The Inhibition Activity of Natural Methoxyflavonoid from Inula britannica on Soluble Epoxide Hydrolase and NO Production in RAW264.7 Cells.

Soluble epoxide hydrolase (sEH) is an enzyme targeted for the treatment of inflammation and cardiovascular diseases. Activated inflammatory cells produce nitric oxide (NO), which induces oxidative stress and exacerbates inflammation. We identify an inhibitor able to suppress sEH and thus NO production. Five flavonoids 1-5 isolated from Inula britannica flowers were evaluated for their abilities to inhibit sEH with IC50 values of 12.1 ± 0.1 to 62.8 ± 1.8 µM and for their effects on enzyme kinetics. A simulation study using computational chemistry was conducted as well. Furthermore, five inhibitors (1-5) were confirmed to suppress NO levels at 10 µM. The results showed that flavonoids 1-5 exhibited inhibitory activity in all tests, with compound 3 exhibiting the most significant efficacy. Thus, in the development of anti-inflammatory inhibitors, compound 3 is a promising natural candidate.

Optimization of Pressurized Liquid Extraction (PLE) Parameters for Extraction of Bioactive Compounds from Moringa oleifera Leaves and Bioactivity Assessment.

Moringa oleifera leaves are rich sources of bioactive compounds with potential health benefits, including antioxidants and anti-inflammatory agents. Pressurized liquid extraction (PLE) stands out as a promising technique for effectively extracting valuable compounds from natural sources. In this study, we aimed to optimize PLE parameters, such as temperature, extraction duration, and pressure, to maximize bioactive compound (polyphenols, flavonoids, and ascorbic acid) yield from M. oleifera leaves and evaluate their antioxidant and anti-inflammatory activities. According to the outcomes of this research, the maximum achieved total polyphenol content was 24.10 mg gallic acid equivalents (GAE)/g of dry weight (dw), and the total flavonoid content was increased up to 19.89 mg rutin equivalents (RtE)/g dw. Moreover, after HPLC-DAD analysis, neochlorogenic and chlorogenic acids, catechin and epicatechin, rutin, and narirutin were identified and quantified. As far as the optimum ascorbic acid content is concerned, it was found to be 4.77 mg/g dw. The antioxidant activity was evaluated by three different methods: ferric reducing antioxidant power (FRAP), the DPPH method, and the anti-hydrogen peroxide activity (AHPA) method, resulting in 124.29 µmol ascorbic acid equivalent (AAE)/g dw, 131.28 µmol AAE/g dw, and 229.38 µmol AAE/g dw values, respectively. Lastly, the albumin denaturation inhibition was found to be 37.54%. These findings underscore the potential of PLE as an efficient extraction method for preparing extracts from M. oleifera leaves with the maximum content of bioactive compounds.

Optimization of Extraction Process and Analysis of Biological Activity of Flavonoids from Leaves of Cultivated 'Qi-Nan' Agarwood.

Currently, the planting of 'Qi-Nan' is continuously increasing, yet a substantial amount of 'Qi-Nan' leaves have not been properly exploited. To improve the 'Qi-Nan' tree 's utilization value, 'Qi-Nan' leaves were used as a raw material. An ultrasound-assisted method was performed to obtain the flavonoids from the 'Qi-Nan' leaves, followed by optimization of the extraction factors using a one-way and response surface methodology to enhance the extraction of flavonoids. Subsequently, the composition of the flavonoids, as well as their bioactive abilities, were analyzed by ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) and in vitro activity testing methods. The findings demonstrated that a 1:50 material-to-liquid ratio, 60% ethanol concentration, and ultrasound-assisted extraction time of 30 min were the ideal procedures for extracting flavonoids (flavonoid content: 6.68%). Meanwhile, the 'Qi-Nan' leaves possessed the antioxidant and medicinal potential to prevent diabetes and Alzheimer 's disease, as evidenced by the semi-inhibitory concentrations (IC50 values) of flavonoid extracts for scavenging DPPH• free radicals, scavenging ABTS•+ free radicals, inhibiting acetylcholinesterase, and inhibiting α-glucosidase, which were 12.64 µg/mL, 66.58 µg/mL, 102.31 µg/mL, and 38.76 µg/mL, respectively, which indicated that the 'Qi-Nan' leaves possessed the properties of antioxidant and medicinal potential for the prevention of Alzheimer 's disease and diabetes.

Optimization of Flavonoid Extraction from Abelmoschus manihot Flowers Using Ultrasonic Techniques: Predictive Modeling through Response Surface Methodology and Deep Neural Network and Biological Activity Assessment.

Understanding the optimal extraction methods for flavonoids from Abelmoschus manihot flowers (AMF) is crucial for unlocking their potential benefits. This study aimed to optimize the efficiency of flavonoid extraction from AMF. After comparing extraction methods, the ultrasonic cell crusher demonstrated superior performance over conventional techniques. Four key factors-solid-to-liquid ratio (1:10 to 1:50 g·mL-1), ethanol concentration (55% to 95%), ultrasonic time (10 to 50 min), and ultrasonic power (5% to 25% of 900 W)-were investigated and normalized using the entropy weight method. This led to a comprehensive evaluation (CE). Optimization of extraction conditions for the ultrasonic cell crusher was achieved through response surface methodology and a deep neural network model, resulting in optimal parameters: ethanol volume fraction of 66%, solid-to-liquid ratio of 1:21 g/mL, extraction efficiency of 9%, and extraction duration of 35 min, yielding a CE value of 23.14 (RSD < 1%). Additionally, the inhibitory effects of the optimized extracts against Streptococcus mutans (S. mutans) were assessed. The results revealed that AMF extract (AMFE) exhibits inhibitory effects on S. mutans, with concomitant inhibition of sucrase and lactate dehydrogenase (LDH). The MIC of AMFE against planktonic S. mutans is 3 mg/mL, with an MBC of 6 mg/mL. Within the concentration range of 1/8 MIC to 2 MIC of AMFE, the activities of sucrase and LDH decreased by 318.934 U/mg prot and 61.844 U/mg prot, respectively. The antioxidant activity of AMFE was assessed using the potassium ferricyanide reduction and phosphomolybdenum methods. Additionally, the effect of AMFE on DPPH, ABTS, and ·OH free radical scavenging abilities was determined. The concentrations at which AMFE exhibited over 90% scavenging rate for ABTS and DPPH free radicals were found to be 0.125 mg/mL and 2 mg/mL, respectively.

Optimizing the Extraction of the Polyphenolic Fraction from Defatted Strawberry Seeds for Tiliroside Isolation Using Accelerated Solvent Extraction Combined with a Box-Behnken Design.

Tiliroside is a natural polyphenolic compound with a wide range of biological activity, and defatted strawberry seeds are its rich source. The goal of this study was to optimize accelerated solvent extraction (ASE) conditions, including temperature, solvent composition, and the number of extraction cycles, using Box-Behnken design to maximize the yield of tiliroside. UPLC-DAD-MS was applied to investigate the polyphenolic composition of the extracts, and preparative liquid chromatography (pLC) was used for isolation. All obtained mathematical models generally showed an increase in the efficiency of isolating polyphenolic compounds with an increase in temperature, ethanol content, and the number of extraction cycles. The optimal established ASE conditions for tiliroside were as follows: a temperature of 65 °C, 63% ethanol in water, and four extraction cycles. This allowed for the obtainment of a tiliroside-rich fraction, and the recovery of isolated tiliroside from plant material reached 243.2 mg from 100 g. Our study showed that ASE ensures the isolation of a tiliroside-rich fraction with high effectiveness. Furthermore, defatted strawberry seeds proved to be a convenient source of tiliroside because the matrix of accompanying components is relatively poor, which facilitates separation.

Exploring Phenolic Compounds Extraction from Saffron (C. sativus) Floral By-Products Using Ultrasound-Assisted Extraction, Deep Eutectic Solvent Extraction, and Subcritical Water Extraction.

Saffron (Crocus sativus) floral by-products are a source of phenolic compounds that can be recovered and used in the nutraceutical, pharmaceutical, or cosmetic industries. This study aimed to evaluate the phenolic compounds' extraction using green extraction techniques (GETs) in saffron floral by-products and to explore the influence of selected extraction techniques on the phytochemical composition of the extracts. Specifically, ultrasound-assisted extraction (UAE), subcritical water extraction (SWE), and deep eutectic solvents extraction (DESE) were used. Phenolic compounds were identified with (HR) LC-ESI-QTOF MS/MS analysis, and the quantitative analysis was performed with HPLC-PDA. Concerning the extraction techniques, UAE showed the highest amount for both anthocyanins and flavonoids with 50:50% v/v ethanol/water as solvent (93.43 ± 4.67 mg/g of dry plant, dp). Among SWE, extraction with 96% ethanol and t = 125 °C gave the best quantitative results. The 16 different solvent mixtures used for the DESE showed the highest amount of flavonoids (110.95 ± 5.55-73.25 ± 3.66 mg/g dp), while anthocyanins were better extracted with choline chloride:butane-1,4-diol (16.0 ± 0.80 mg/g dp). Consequently, GETs can be employed to extract the bioactive compounds from saffron floral by-products, implementing recycling and reduction of waste and fitting into the broader circular economy discussion.