The changed structures of Cyperus esculentus protein decide its modified physicochemical characters: Effects of ball-milling, high pressure homogenization and cold plasma treatments on structural and functional properties of the protein.

Three physical treatments, including ball-milling (BM), high pressure homogenization (HPH) and cold plasma (CP) were applied to modify structural and functional properties of Cyperus esculentus protein (CEP). The results showed that three treatments significantly altered morphology and reduced particle size of CEP. Both primary and secondary structures of CEP were hardly changed, while disulfide bonds and hydrophobic forces between amino acid residues of CEP were interrupted by three treatments, releasing free sulfhydryls and hydrophobic groups. With the free moiety accumulation, the reformed interactions between them enhanced the crystallinity and thermostability of CEP. Besides, solubility and emulsifying properties of CEP were significantly improved within a certain range of treatment duration and intensity, and three treatments decreased water but increased oil holding capacity of CEP. Conclusively, the modified physicochemical properties of CEP were decided by the changed molecular structures of CEP, and different treatments may satisfy different processing requirements for the protein.

Development of quinoa (Chenopodium quinoa Willd) protein isolate-gum Arabic conjugates via ultrasound-assisted wet heating for spice essential oils emulsification: Effects on water solubility, bioactivity, and sensory stimulation.

Quinoa protein isolate-gum Arabic (QPI-GA) conjugates were developed by ultrasound-assisted wet heating to improve the water solubility and bioactivity of spice essential oils (EOs) in this study. The optimal conditions for QPI-GA conjugates preparation were found to be: heating temperature of 72 ℃, ultrasound power of 450 W, and reaction time of 46 min. QPI-GA conjugates displayed significantly higher emulsifying efficiency and stronger tolerance to pH variation, high salt concentration, and storage than raw materials. The emulsifying efficiency of emulsions was also influenced by the pH and viscosity of EOs, zeta potential of the emulsion as well as the relative density and lipid/water partition coefficient (P) of EOs were the possible factors impacting the stability of EO emulsions. The water solubility, antioxidant ability, and antibacterial ability of tested EOs were improved after emulsification. Meanwhile, encapsulation with QPI-GA conjugates played a good effect on reducing the sensory stimulation of EOs.

Mechanism of feed moisture levels in extrusion treatment to improve the instant properties of Chinese yam (Dioscorea opposita Thunb.) flour.

Extruded yam flour was prepared at different feed moisture to improve its instant properties. The water solubility index (WSI) and water absorption index (WAI) were used to compare the instant properties of yam flour. Their chemical compositions, particle size distribution, crystalline structure, and microscopic forms were also analyzed to assess the effects of feed moisture on the instant properties of yam flour. We found that extrusion significantly improved the instant properties of yam flour, while the WSI value increased from 29.50% to 71.86% and the WAI value decreased from 387.88% to 228.06% with decreased feed moisture. Extrusion led to the degradation of total starch and amylopectin, and the contents of soluble substances increased markedly. Extrusion destroyed the granular and crystalline structures, which were reconstituted as amylose-lipid complexes with a significant decrease in relative crystallinity. Increasing the feed moisture was beneficial to the flow and color retention, while lower feed moisture was more favorable to enhance the instant properties.

Development of Delayed Release Oral Formulation Comprising Esomeprazole Spray Dried Dispersion Utilizing Design of Experiment As An Optimization Strategy.

Solid dispersion (SD) technology is one of the most widely preferred solubility enhancement methods, especially for Biopharmaceutics classification system class II and IV drugs. Since the last decade, its application for the dual purpose of solubility hike and modified release using novel carriers has been in demand for its added advantages. Spray drying is a commercially accepted technique with high aspects of scalability and product characteristics. The current study used spray-dried dispersion to design delayed release capsule for the proton pump inhibitor esomeprazole. The SD carrier hydroxypropyl methylcellulose acetate succinate-medium grade (HPMCAS-MF) enhanced solubility, inhibited precipitation of saturated drug solutions, and allowed enteric release owing to its solubility above pH 6. The proposed approach avoided compression, coating with enteric polymers, and the development of multi-particulate pellet-based formulations, improving manufacturing feasibility. The formulation was optimized using Box-Behnken design, considering significant formulation variables like HPMCAS-MF proportion and critical process parameters like feed flow rate and inlet temperature. The optimized spray-dried dispersion were characterized based on Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM) and also evaluated for solubility, in vitro drug release, residual solvent content, and stability testing. Response surface methodology optimization anticipated that formulation variables affected solubility and release profile, whereas CPPs affected yield. The design space was developed via overlay plot based on constraints specified to attain the desired response and validated using three checkpoint batches with desirability 1. FTIR showed active pharmaceutical ingredient-polymer compatibility. Particle size and SEM studies showed spherical particles with an average Z-value of 1.8 µ. DSC and PXRD confirmed SD's amorphous nature. The drug release investigation and release kinetics prediction utilizing DD-solver software showed a 2-h lag time with > 90% cumulative drug release up to 4 h for the DR formulation. ESM SDD were prepared by spray drying technique using the novel solid dispersion carrier HPMCAS-MF to serve the dual purpose of solubility enhancement and delayed release. The ratio of API:carrier and process variables like feed flow rate and inlet temperature were varied using the Box-Behnken Design to determine the design space of optimized product to procure the desired characteristics of solubility improvement compared to crystalline API and delayed release of PPI to avoid the degradation in the gastric environment. The developed formulation represents several benefits over the already existing marketed products.

Adapting physiologically-based pharmacokinetic models for machine learning applications.

Both machine learning and physiologically-based pharmacokinetic models are becoming essential components of the drug development process. Integrating the predictive capabilities of physiologically-based pharmacokinetic (PBPK) models within machine learning (ML) pipelines could offer significant benefits in improving the accuracy and scope of drug screening and evaluation procedures. Here, we describe the development and testing of a self-contained machine learning module capable of faithfully recapitulating summary pharmacokinetic (PK) parameters produced by a full PBPK model, given a set of input drug-specific and regimen-specific information. Because of its widespread use in characterizing the disposition of orally administered drugs, the PBPK model chosen to demonstrate the methodology was an open-source implementation of a state-of-the-art compartmental and transit model called OpenCAT. The model was tested for drug formulations spanning a large range of solubility and absorption characteristics, and was evaluated for concordance against predictions of OpenCAT and relevant experimental data. In general, the values predicted by the ML models were within 20% of those of the PBPK model across the range of drug and formulation properties. However, summary PK parameter predictions from both the ML model and full PBPK model were occasionally poor with respect to those derived from experiments, suggesting deficiencies in the underlying PBPK model.

Integrated Protein Solubility Shift Assays for Comprehensive Drug Target Identification on a Proteome-Wide Scale.

Target proteins are often stabilized after binding with a ligand and thereby typically become more resistant to denaturation. Based on this phenomenon, several methods without the need to covalently modify the ligand have been developed to identify target proteins for a specific ligand. These methods usually employ complicated workflows with high cost and limited throughput. Here, we develop an iso-pH shift assay (ipHSA) method, a proteome-wide target identification method that detects ligand-induced protein solubility shifts by precipitating proteins with a single concentration of acidic agent followed by protein quantification via data-independent acquisition (DIA). Using a pan-kinase inhibitor, staurosporine, we demonstrated that ipHSA increased throughput compared to the previously developed pH-dependent protein precipitation (pHDPP) method. ipHSA was found to have high complementarity in staurosporine target identification compared with the improved isothermal shift assay (iTSA) and isosolvent shift assay (iSSA) using DIA instead of tandem mass tags (TMTs) for quantification. To further improve target identification sensitivity, we developed an integrated protein solubility shift assay (IPSSA) by pooling the supernatants yielded from ipHSA, iTSA, and iSSA methods. IPSSA exhibited increased sensitivity in screening staurosporine targets by 38, 29, and 38% compared to individual methods. Increasing the number of replicate experiments further enhanced the sensitivity of target identification. Meanwhile, IPSSA also improved the throughput and reduced the cost compared with previous methods. As a fast and efficient tool for drug target identification, IPSSA is expected to have broad applications in the study of the mechanism of action.

Solubility of lamotrigine in age-specific biorelevant media that simulated the fasted- and fed-conditions of the gastric and intestinal environments in pediatrics and adults: implications for traditional, re-formulated, modified, and new oral formulations.

BACKGROUND: Lamotrigine is an effective antiseizure medication that can be used in the management of focal and generalized epilepsies in pediatric patients. This study was conducted to quantify and compare the solubility of lamotrigine in age-specific biorelevant media that simulated the fasted and fed conditions of the gastric and intestinal environments in pediatrics and adults. Another aim was to predict how traditional, re-formulated, modified, and new oral formulations would behave in the gastric and intestinal environments across different age groups. METHODS: Solubility studies of lamotrigine were conducted in 16 different age-specific biorelevant media over the pH range and temperature specified by the current biopharmaceutical classification system-based criteria. The age-specific biorelevant media simulated the environments in the stomach and proximal gastrointestinal tract in both fasted and fed conditions of adults and pediatric sub-populations. The solubility of lamotrigine was determined using a pre-validated HPLC-UV method. RESULTS: Lamotrigine showed low solubility in the 16 age-specific biorelevant media as indicated by a dose number of > 1. There were significant age-specific variabilities in the solubility of lamotrigine in the different age-specific biorelevant media. Pediatric/adult solubility ratios of lamotrigine fell outside the 80-125% range in 6 (50.0%) and were borderline in 3 (25.0%) out of the 12 compared media. These ratios indicated that the solubility of lamotrigine showed considerable differences in 9 out of the 12 (75.0%) of the compared media. CONCLUSION: Future studies are still needed to generate more pediatric biopharmaceutical data to help understand the performances of oral dosage forms in pediatric sub-populations.

Contribution of Insoluble Bound Antioxidants from Germinated Seeds of Wheat and Spelt to the Nutritional Value of White Bread.

This research aimed to study the dynamic changes in phenolic antioxidants between the germ and the rest of the germinated seed of wheat and spelt and to evaluate the whole grain flour from germinated seeds as a functional supplement. Longer germination resulted in higher TPC, DPPH, and ABTS values when considering the entire germinated seed, while the optimal germination time was not consistent when considering the germ and the remaining germinated seed separately. While in the germinated seed (without germ) the majority of TPC was determined to be bound phenolics (up to 92%), the extractable form dominated in the germ (up to 69%). The most abundant phenolic antioxidants in germinated wheat and spelt seeds, trans-ferulic acid, cis-ferulic acid, and p-coumaric acid, increased significantly with germination. Only breads with 5% germinated spelt or wheat flour were suitable for the production of a food product, showing higher extractable TPC, antioxidant activity, individual phenolic acids, and improved specific volume, and were preferred because of their appearance, aroma, and color. The PCA biplot showed that the addition of 15% and 30% germinated flours had the greatest positive impact on phenolic properties, while breads with the addition of 5% germinated flour had the greatest positive impact on specific volume and color.

The emerging role of ATP as a cosolute for biomolecular processes.

ATP is an important small molecule that appears at outstandingly high concentration within the cellular medium. Apart from its use as a source of energy and a metabolite, there is increasing evidence for important functions as a cosolute for biomolecular processes. Owned to its solubilizing kosmotropic triphosphate and hydrophobic adenine moieties, ATP is a versatile cosolute that can interact with biomolecules in various ways. We here use three models to categorize these interactions and apply them to review recent studies. We focus on the impact of ATP on biomolecular solubility, folding stability and phase transitions. This leads us to possible implications and therapeutic interventions in neurodegenerative diseases.

Improving the anti-HIV-1 activity and solubility of poorly water-soluble DAPYs by heteroaromatic replacement strategy: From naphthalene-DAPYs to quinoline-DAPYs.

To enhance the anti-HIV-1 efficacy and solubility of our previously documented NNRTI 1, a collection of innovative quinoline-substituted DAPY derivatives were devised using heteroaromatic replacement strategy. The results of biological evaluation revealed that the representative compound 5h possessed the highest inhibitory activity against wild-type HIV-1 and selectivity index (EC50 = 0.0018 µM, SI > 166667), which were obviously better than that of 1 (EC50 = 0.00978 µM, SI > 37764), NVP (EC50 = 0.059 µM, SI > 158), EFV (EC50 = 0.028 µM, SI > 269), and ETR (EC50 = 0.0029 µM, SI > 1519). The water solubility of compound 5h was remarkably improved, surpassing that of 1, ETR and RPV. Additionally, this compound exerted significantly enhanced anti-resistance potency, compared to 1, and displayed comparable activity to ETR against WT RT of HIV-1 (IC50 = 0.011 µM). To elucidate the underlying molecular mechanisms, molecular docking studies were conducted to investigate the crucial interactions between 5h and WT/mutant strains of HIV-1. These findings provide valuable insights and drive further advancements in the development of DAPYs for HIV therapy.

Nano-based formulations of curcumin: elucidating the potential benefits and future prospects in skin cancer.

Skin cancer refers to any malignant lesions that occur in the skin and are observed predominantly in populations of European descent. Conventional treatment modalities such as excision biopsy, chemotherapy, radiotherapy, immunotherapy, electrodesiccation, and photodynamic therapy (PDT) induce several unintended side effects which affect a patient's quality of life and physical well-being. Therefore, spice-derived nutraceuticals like curcumin, which are well tolerated, less expensive, and relatively safe, have been considered a promising agent for skin cancer treatment. Curcumin, a chemical constituent extracted from the Indian spice, turmeric, and its analogues has been used in various mammalian cancers including skin cancer. Curcumin has anti-neoplastic activity by triggering the process of apoptosis and preventing the multiplication and infiltration of the cancer cells by inhibiting some signaling pathways and thus subsequently preventing the process of carcinogenesis. Curcumin is also a photosensitizer and has been used in PDT. The major limitations associated with curcumin are poor bioavailability, instability, limited permeation into the skin, and lack of solubility in water. This will constrain the use of curcumin in clinical settings. Hence, developing a proper formulation that can ideally release curcumin to its targeted site is important. So, several nanoformulations based on curcumin have been established such as nanogels, nanoemulsions, nanofibers, nanopatterned films, nanoliposomes and nanoniosomes, nanodisks, and cyclodextrins. The present review mainly focuses on curcumin and its analogues as therapeutic agents for treating different types of skin cancers. The significance of using various nanoformulations as well non-nanoformulations loaded with curcumin as an effective treatment modality for skin cancer is also emphasized.

Nanosuspension encapsulated chitosan-pectin microbeads as a novel delivery platform for enhancing oral bioavailability.

The current study aimed to overcome the poor solubility and colon-specific delivery of curcumin (CUR) by formulating a curcumin nanosuspension (CUR-NS) using the antisolvent precipitation method. Freeze-dried CUR-NS was encapsulated into microbeads (CUR-NS-MB) by the ionotropic gelation method using zinc chloride (as a cross-linking agent) with the help of rate-controlling polymers, pectin, and chitosan. Furthermore, cellulose acetate phthalate (CAP) is incorporated as an enteric polymer to protect against acidic medium degradation. Particle size, surface morphology, interaction studies, and entrapment studies were performed to optimize CUR-NSs. Nanosuspensions stabilized with hydroxypropyl methylcellulose (HPMC E-15; 1 % w/v) showed an average particle size of 193.5 ± 4.31 nm and a polydispersity index (PDI) of 0.261 ± 0.020. The optimized microbeads (CUR-NS-MB) showed 89.45 ± 3.11 % entrapment efficiency with a drug loading of 14.54 ± 1.02 %. The optimized formulation (CUR-NS-MB) showed colon-specific in vitro drug release bypassing acid pH degradation. In animal studies, a 2.5-fold increase in Cmax and a 4.4-fold increase in AUC048h were observed with CUR-NS-MB, which was more significant than that of plain CUR. Therefore, the developed CUR-NS-MB has the potential to be used as a colon-specific delivery system.

Composites of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide with Polymers: Effect of Crystallinity on Solubility and Stability.

This work aimed to develop and characterize a water-soluble, high-release active pharmaceutical ingredient (API) composite based on the practically water-insoluble API N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-3), a substance with antidepressant and anxiolytic action. This allows to ensure the bioavailability of the medicinal product of combined action. Composites obtained by the method of creating amorphous solid dispersions, where polyvinylpyrrolidone (PVP) or Soluplus® was used as a polymer, were studied for crystallinity, stability and the release of API from the composite into purified water. The resulting differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and dissolution test data indicate that the resulting composites are amorphous at 1:15 API: polymer ratios for PVP and 1:5 for Soluplus®, which ensures the solubility of GML-3 in purified water and maintaining the supercritical state in solution.

Unravelling the Role of Uncommon Hydrogen Bonds in Cyclodextrin Ferrociphenol Supramolecular Complexes: A Computational Modelling and Experimental Study.

We sought to determine the cyclodextrins (CDs) best suited to solubilize a patented succinimido-ferrocidiphenol (SuccFerr), a compound from the ferrociphenol family having powerful anticancer activity but low water solubility. Phase solubility experiments and computational modelling were carried out on various CDs. For the latter, several CD-SuccFerr complexes were built starting from combinations of one or two CD(s) where the methylation of CD oxygen atoms was systematically changed to end up with a database of ca. 13 k models. Modelling and phase solubility experiments seem to indicate the predominance of supramolecular assemblies of SuccFerr with two CDs and the superiority of randomly methylated ß-cyclodextrins (RAMEßCDs). In addition, modelling shows that there are several competing combinations of inserted moieties of SuccFerr. Furthermore, the models show that ferrocene can contribute to high stabilization by making atypical hydrogen bonds between Fe and the hydroxyl groups of CDs (single bond with one OH or clamp with two OH of the same glucose unit).

Development and In Vitro-In Vivo Correlation Evaluation of IMM-H014 Extended-Release Tablets for the Treatment of Fatty Liver Disease.

This study aimed to develop extended-release tablets containing 25 mg IMM-H014, an original drug formulated by a direct powder pressing method based on pharmaceutical-grade hydrophilic matrix polymers such as hydroxypropyl methylcellulose, to establish an in vitro-in vivo correlation (IVIVC) to predict bioavailability. The tablets' mechanical properties and in vitro and in vivo performance were studied. The formulation was optimized using a single-factor experiment and the reproducibility was confirmed. The in vitro dissolution profiles of the tablet were determined in five dissolution media, in which the drug released from the hydrophilic tablets followed the Ritger-Peppas model kinetics in 0.01 N HCl medium for the first 2 h, and in phosphate-buffered saline medium (pH 7.5) for a further 24 h. Accelerated stability studies (40 °C, 75% relative humidity) proved that the optimal formulation was stable for 6 months. The in vivo pharmacokinetics study in beagle dogs showed that compared to the IMM-H014 immediate release preparation, the maximum plasma concentration of the extended-release (ER) preparation was significantly decreased, while the maximum time to peak and mean residence time were significantly prolonged. The relative bioavailability was 97.9% based on the area under curve, indicating that the optimal formulation has an obvious ER profile, and a good IVIVC was established, which could be used to predict in vivo pharmacokinetics based on the formulation composition.

A Novel Betulinic Acid Analogue: Synthesis, Solubility, Antitumor Activity and Pharmacokinetic Study in Rats.

Betulinic acid (BA) and betulin (BE) are naturally pentacyclic triterpenes with documented biological activities, especially antitumor and anti-inflammatory activity. However, their bioavailability in vivo is not satisfactory in terms of medical applications. Thus, to improve the solubility and bioavailability so as to improve the efficacy, 28-O-succinyl betulin (SBE), a succinyl derivative of BE, was synthesized and its solubility, in vitro and in vivo anti-tumor activities, the apoptosis pathway as well as the pharmacokinetic properties were investigated. The results showed that SBE exhibited significantly higher solubility in most of the tested solvents, and showed a maximum solubility of 7.19 ± 0.66 g/L in n-butanol. In vitro and in vivo anti-tumor activity assays indicated both BA and SBE exhibited good anti-tumor activities, and SBE demonstrated better potential compared to BA. An increase in the ratio of Bad/Bcl-xL and activation of caspase 9 was found in SBE treated Hela cells, suggesting that the intrinsic mitochondrial pathway is involved in SBE induced apoptosis. Compared with BA, SBE showed much-improved absorption and bioavailability in pharmacokinetic studies.

Herbicide and Cytogenotoxic Activity of Inclusion Complexes of Psidium gaudichaudianum Leaf Essential Oil and ß-Caryophyllene on 2-Hydroxypropyl-ß-cyclodextrin.

The present investigation aimed to develop inclusion complexes (ICs) from Psidium gaudichaudianum (GAU) essential oil (EO) and its major compound ß-caryophyllene (ß-CAR), and to evaluate their herbicidal (against Lolium multiflorum and Bidens pilosa) and cytogenotoxic (on Lactuca sativa) activities. The ICs were obtained using 2-hydroxypropyl-ß-cyclodextrin (HPßCD) and they were prepared to avoid or reduce the volatility and degradation of GAU EO and ß-CAR. The ICs obtained showed a complexation efficiency of 91.5 and 83.9% for GAU EO and ß-CAR, respectively. The IC of GAU EO at a concentration of 3000 µg mL-1 displayed a significant effect against weed species B. pilosa and L. multiflorum. However, the ß-CAR IC at a concentration of 3000 µg mL-1 was effective only on L. multiflorum. In addition, the cytogenotoxic activity evaluation revealed that there was a reduction in the mitotic index and an increase in chromosomal abnormalities. The produced ICs were able to protect the EO and ß-CAR from volatility and degradation, with a high thermal stability, and they also enabled the solubilization of the EO and ß-CAR in water without the addition of an organic solvent. Therefore, it is possible to indicate the obtained products as potential candidates for commercial exploration since the ICs allow the complexed EO to exhibit a more stable chemical constitution than pure EO under storage conditions.

A machine learning approach for thermodynamic modeling of the statically measured solubility of nilotinib hydrochloride monohydrate (anti-cancer drug) in supercritical CO2.

Nilotinib hydrochloride monohydrate (NHM) is an anti-cancer drug whose solubility was statically determined in supercritical carbon dioxide (SC-CO2) for the first time at various temperatures (308-338 K) and pressures (120-270 bar). The mole fraction of the drug dissolved in SC-CO2 ranged from 0.1 × 10-5 to 0.59 × 10-5, corresponding to the solubility range of 0.016-0.094 g/L. Four sets of models were employed to evaluate the correlation of experimental data; (1) ten empirical and semi-empirical models with three to six adjustable parameters, such as Chrastil, Bartle, Sparks, Sodeifian, Mendez-Santiago and Teja (MST), Bian, Jouyban, Garlapati-Madras, Gordillo, and Jafari-Nejad; (2) Peng-Robinson equation of state (Van der Waals mixing rule, had an AARD% of 10.73); (3) expanded liquid theory (modified Wilson model, on average, the AARD of this model was 11.28%); and (4) machine learning (ML) algorithms (random forest, decision trees, multilayer perceptron, and deep neural network with respective R2 values of 0.9933, 0.9799, 0.9724 and 0.9701). All the models showed an acceptable agreement with the experimental data, among them, the Bian model exhibited excellent performance with an AARD% of 8.11. Finally, the vaporization (73.49 kJ/mol) and solvation (- 21.14 kJ/mol) enthalpies were also calculated for the first time.

A modified strategy to improve the dissolution of flavonoids from Artemisiae Argyi Folium using ultrasonic-assisted enzyme-deep eutectic solvent system.

In this study, enzyme-deep eutectic solvent-assisted ultrasonic extraction technique (EnDUE) was developed for the efficient dissolution of flavonoids from Artemisiae Argyi Folium. The extraction results of Artemisiae Argyi Folium flavonoids (quercetin, luteolin, and isorhamnetin) were used as indicators to investigate the influencing factors through single factor experiment, Placket-burman design, and Box-behnken design, so as to obtain satisfactory yields. After systematic optimization, the optimal conditions for extraction of the target flavonoids were: Choline chloride/1,4-butanediol with a water content of 25%, cellulase+pectinase with a concentration of 1.6%, solid-liquid ratio of 1/32 g/mL, pH of 4.2, ultrasonic frequency of 80 kHz, ultrasonic power of 160 W, ultrasonic temperature of 40 °C, and ultrasonic time of 25 min, respectively, which derived a total yield of 8.06 ± 0.29 mg/g. Compared with the reference techniques, the proposed EnDUE technique showed significant advantages in the yield and extraction efficiency of flavonoids. In addition, after preliminary purification, the Artemisiae Argyi Folium flavonoids showed good antioxidant activity. Deep eutectic solvent (DES) can degrade the cell wall components and increase the action site of enzyme, and enzyme can promote the penetration of DES into the cell wall matrix, which is mutually beneficial to the dissolution of intracellular components. Therefore, the extraction technique proposed in this work (EnDUE) greatly promotes the dissolution of flavonoids from Artemisiae Argyi Folium, and provides theoretical support for the further application of plant flavonoids.