Aglycone Part Research Articles

Unveiling the Molecular Mechanism of Diosmetin and its Impact on Multifaceted Cellular Signaling Pathways.

Diosmetin is an O-methylated flavone and the aglycone part of the flavonoid glycosides diosmin that occurs naturally in citrus fruits. Pharmacologically, diosmetin is reported to exhibit anticancer, antimicrobial, antioxidant, oestrogenic, and anti-inflammatory activities. This comprehensive review was aimed to critically explore diverse pharmacological activities exhibited by diosmetin. Along with that, this review can also identify potential research areas with an elucidation of the multifactorial underlying signaling mechanism of action of diosmetin in different diseases. A comprehensive collection of evidence and insights was obtained from scientific journals and books from physical libraries and electronic platforms like Google Scholar and PubMed. The time frame selected was from year 1992 to July 2023. The review delves into diosmetin's impact on cellular signaling pathways and its potential in various diseases. Due to its ability to modulate signaling pathways and reduce oxidative stress, it can be suggested as a potential versatile therapeutic agent for mitigating oxidative stressassociated pathogenesis. The amalgamation of the review underscores diosmetin's promising role as a multifaceted therapeutic agent, highlighting its potential for drug development and clinical applications.

Absolute Configuration Determination of Sugar: A Review of the Different Methods

Determination of the stereochemistry of the stereocenter from the aglyconic part of carbohydrates is always one of the most important tasks for chemistry carbohydrates researchers. The absolute configuration (AC), a challenge for synthetic chemists, has attracted much attention. During the past few decades, many techniques and approaches have been developed to determine the AC of carbohydrates, including methods of X-ray diffraction (XRD), electronic and vibrational circular dichroism (ECD and VCD), Raman optical activity (ROA), nuclear magnetic resonance (NMR) utilizing anisotropic effects of chiral derivatizing agents, and quantum chemical calculations. On the other hand, none of the currently applied techniques can dominate AC determination, since they each have their respective limitations corresponding to the different structural features. This review summarizes most of the techniques and methods commonly used in AC assignment of carbohydrates (but specifically glycosides), in the last decades (2000-2023).
 GRAPHICAL ABSTRACT

Anticandedal Effect action of Different Concentrations of Aglycon fraction of Anthroquinon (monoanathron) isolated from Aloe vera on Heat cure Acrylic Resins

Aim of study: to investigate the effects of different concentrations of aloe vera , aglycon part (monoanathron ) against candida albicance adhere to two types of heat cure acrylic resin denture base (conventional and Hi- impact) on two periods of time (30 minutes and 8 hours).
 Materials & methods: A total of 120 specimens were prepared, sixty specimens of each hot cure denture base acrylic resin material, each sixty specimens were farther divided into two subgroups of 30 specimens according to the time of immersion, each 30 specimens were farther subdivided into three 10 specimen groups according to the concentration of aleo vera used, isolation of free aglycon (Monoianthron) from anthroquinon glycoside of aloe vera plant; Candida albicans isolation and identification and preparation of candida albicans suspension; autoclaved specimens of each sub-group for both heat cure acrylic resins were placed into the tubes containing brain heart infusion plus inoculum and remained for 12 hours at 37 0C in order to favor an initial colonization of the acrylic resin surfaces, the disinfection step was performed over two periods, colony formation was then counted after incubation.
 Results: The two concentration of aloe Vera studied in the present investigation exhibited varying degree of inhibitory effect against candida albicans adherent to different type of heat cure denture base acrylic resins. The degree of inhibition varied depending on the concentration of the extract while the period of immersion has no significant effect on the number colony.
 Conclusion: with the limitation of this study it can be concluded that 100% and 75% concentrations of monoanthron aglycon part of anthroquinon isolated from aloe vera have anticandidal effect, 100%concentration has higher effect than75%. Immertion period has no effect on the anticandidal activity of the solutions.

Gymnemagenin a Promising Drug Candidate for Management of Hyperglycemia: In-Vitro and In-Vivo Study

Background: Diabetes mellitus is a chronic metabolic disorder resulting from absolute or relative impairments in β-cell functions, insulin resistance, or both and has been exceptionally increasing worldwide. Gymnema sylvestre is an important traditional plant used for the treatment and management of diabetes. Gymnemagenin is an aglycone part of gymnemic acids which is a bioactive component of G. sylvestre. The objective of the present study was to undertake in-vitro and in-vivo studies to generate a stronger biochemical rationale for the management of diabetes mellitus. Results: The result of the preliminary in-vitro study of gymnemagenin suggested further evaluation of the inhibition of key enzymes related to carbohydrate metabolism. Gymnemagenin showed strong α-amylase (IC50 1.17±0.02 mg/mL) and strong α-glucosidase (IC50 2.04±0.17mg/mL) inhibitory activity. The positive in-vitro enzyme inhibition tests paved the way for confirmatory in-vivo studies. The in-vivo studies demonstrated that gymnemagenin (20 mg/kg, b.w.) given orally significantly (P<0.01) reduced area under curve (AUC) in mice when challenged with oral administration of starch and sucrose separately. The reduction in AUC by gymnemagenin was comparable to that of acarbose (10 mg/kg, b.w., p.o.). Conclusion: The research findings clearly supported the traditional use of G. sylvestre in the treatment of diabetes mellitus.

The Custom R Group Enumeration with Various R Group Libraries at Designated Sites on Amphotericin B.

Amphotericin B is a gold-standard drug, particularly for the treatment of systemic fungal infections. However, its low solubility and permeability limit its application. To improve its bioavailability, AmB may be conjugated with various water-soluble auxiliary groups. Custom R group Enumeration was used at the designated sites of Amphotericin B. The designated sites taken into consideration are the carboxyl moiety of the aglycone part and the amine moiety of the glycone part of Amphotericin B for Enumeration purposes. The enumerated molecules were subjected to QikProp properties. We identified fourteen hits with improved predicted aqueous solubility and cell permeability. Enumeration might be applicable in improving bioavailability, which could lead to the oral formulation of the Amphotericin B drug.

C-H Glycosylation of Native Carboxylic Acids: Discovery of Antidiabetic SGLT-2 Inhibitors.

C-Glycosides are critical motifs embedded in many bioactive natural products. The inert C-glycosides are privileged structures for developing therapeutic agents owing to their high chemical and metabolic stability. Despite the comprehensive strategies and tactics established in the past few decades, highly efficient C-glycoside syntheses via C-C coupling with excellent regio-, chemo-, and stereoselectivity are still needed. Here, we report the efficient Pd-catalyzed glycosylation of C-H bonds promoted by weak coordination with native carboxylic acids without external directing groups to install various glycals to the structurally diverse aglycon parts. Mechanistic evidence points to the participation of a glycal radical donor in the C-H coupling reaction. The method has been applied to a wide range of substrates (over 60 examples), including many marketed drug molecules. Natural product- or drug-like scaffolds with compelling bioactivities have been constructed using a late-stage diversification strategy. Remarkably, a new potent sodium-glucose cotransporter-2 inhibitor with antidiabetic potential has been discovered, and the pharmacokinetic/pharmacodynamic profiles of drug molecules have been changed using our C-H glycosylation approach. The method developed here provides a powerful tool for efficiently synthesizing C-glycosides to facilitate drug discovery.

Metabolomics as a Potential Chemotaxonomical Tool: Application on the Selected Euphorbia Species Growing Wild in Serbia.

Chemotaxonomy presents various challenges that need to be overcome in order to obtain valid and reliable results. Individual genetic and environmental variations can give a false picture and lead to wrong conclusions. Applying a holistic approach, based on multivariate data analysis, these challenges can be overcome. Thus, a metabolomics approach has to be optimized depending on the subject of research. We used 1H NMR-based metabolomics as a potential chemotaxonomic tool on the selected Euphorbia species growing wild in Serbia. Principal components analysis (PCA), soft independent modeling by class analogy (SIMCA) and Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) were used to analyze obtained NMR data in order to reveal chemotaxonomic biomarkers. The standard protocol for plant metabolomics was optimized aiming to extract more specific metabolites, which are characteristic for the Euphorbia genus. The obtained models were validated, which revealed that variables unique for each species were associated with certain classes of molecules according to literature data. In E. salicifolia, acacetin-7-O-glycoside (not found before in the species) was detected, and the structure of the aglycone part was solved based on 2D NMR data. In the presented paper, we have shown that metabolomics can be successfully used in Euphorbia chemotaxonomy.

Click mediated synthesis of functionalized glycolipids with peptide-peptoid linkages

The present work describes the synthesis of a new class of glycolipids with systematic variations in the linkage region, as well as in the aglycon part using Cu(I) catalyzed click reaction. The linkage region between sugar and the aglycon part was diversified using amide, amido-triazole and 5-benzoyl triazole moieties. The structural diversity of glycolipids was further amplified by incorporating several polar peptide foldamer groups such as triazole, amide, peptide, or N-aryl peptoid in the aglycon part. The newly designed glycolipids were derived from the amalgamation of different peptide bond mimics. This work reports the first use of N-aryl peptoid in the synthesis of glycolipids. The newly synthesized glycolipids were characterized using different spectroscopic and spectrometric analyses. The impact of the amide bond as well as the triazole ring in the linkage region on the morphology of the glycolipids was analysed by comparing their self-assemblies using SEM analysis. The geometries of the glycolipids were also optimized using density functional theory and the optimized structures were found to be minima in the potential energy surfaces.

Mechanistic Insights of Rutin against Metabolic Disorders

Rutin, a quercetin glycoside comes under the class flavonol. The aglycone part of rutin is known as quercetin. It is found in numerous fruits and plants, especially apricots, buckwheat, cherries, grapefruit, grapes, oranges, and plums. Rutin shows cardioprotective, neuroprotective, and nephroprotective effects mediated via its antioxidant mechanism. The neuroprotective effect of rutin is utilized in the treatment of Parkinson’s disease. It has been documented in the scientific literature that rutin improves obesity through brown fat activation, modulates DNA damage signaling in cancer cells, reduces inflammation by inhibiting eicosanoid biosynthesis, lipoxygenase, cyclooxygenase, and phospholipase A2 activities, enhances insulin release as well as decreases the expression of resistin along with increases the expression of PPAR γ in diabetic patients, increases total cholesterol, high-density lipoprotein and very low-density lipoprotein levels, whereas low-density lipoprotein level decreases resulting into antilipidemic activity, inhibits diabetic liver injury and diabetic cardiomyopathy. Repurposing of rutin was also done against SARS-CoV-2. Our study aims to survey the most recent progress with emphasis on how rutin adapts intracellular signaling cascades to treat different metabolic disorders. However, the precise cellular and molecular mechanisms of rutin are known and more clinical studies are required to provide a novel therapeutic approach for the treatment of metabolic disorders.

The Chemistry and the Anti-Inflammatory Activity of Polymethoxyflavonoids from Citrus Genus.

Polymethoxyflavonoids (PMFs) are a large group of compounds belonging to the more general class of flavonoids that possess a flavan carbon framework decorated with a variable number of methoxy groups. Hydroxylated polymethoxyflavonoids (HPMFs), instead, are characterized by the presence of both hydroxyl and methoxy groups in their structural unities. Some of these compounds are the aglycone part in a glycoside structure in which the glycosidic linkage can involve the -OH at various positions. These compounds are particular to Citrus genus plants, especially in fruits, and they are present mainly in the peel. A considerable number of PMFs and HPMFs have shown promising biological activities and they are considered to be important nutraceuticals, responsible for some of the known beneficial effects on health associated with a regular consumption of Citrus fruits. Among their several actions on human health, it is notable that the relevant contribution in controlling the intracellular redox imbalance is associated with the inflammation processes. In this work, we aim to describe the status concerning the chemical identification and the anti-inflammatory activity of both PMFs and HPMFs. In particular, all of the chemical entities unambiguously identified by isolation and complete NMR analysis, and for which a biochemical evaluation on the pure compound was performed, are included in this paper.

Novel Sesquiterpene and Diterpene Aminoglycosides from the Deep-Sea-Sediment Fungus Trichoderma sp. SCSIOW21.

Six new sesquiterpene aminoglycosides, trichaspside F (2) and cyclonerosides A-E (5-9), two new diterpene aminoglycosides, harzianosides A and B (10, 11), and three known sesquiterpenes, trichodermoside (1), cycloneran-3,7,10,11-tetraol (3), and cyclonerodiol (4), have been isolated from the n-butanol extract of Trichoderma sp. SCSIOW21 (Hypocreaceae), a deep-sea-sediment-derived fungus. The structures and relative configurations of the new compounds were determined using spectroscopic techniques and comparisons with those reported in the literature. The absolute configurations of the aglycone part of cyclonerosides A-E (5-9) were tentatively proposed based on optical rotation and biogenic considerations. Cyclonerosides A-E (5-9) represent the first glycosides of cyclonelane-type sesquiterpenes generated from Trichoderma. The NO-production-inhibitory activities were evaluated using macrophage RAW264.7 cells. Among the isolated compounds, trichaspside F (2) and cyclonerosides B-E (6-9) exhibited the strongest NO-production-inhibitory activities with IC50 values of 54.8, 50.7, 57.1, 42.0, and 48.0 µM, respectively, compared to the IC50 value of 30.8 µM for the positive control (quercetin). When tested for anti-fungal activities against several pathogenic fungi, none of the compounds exhibited significant activities at a concentration of 100 µM.

Alzheimer's Disease as a Major Public Health Concern: Role of Dietary Saponins in Mitigating Neurodegenerative Disorders and Their Underlying Mechanisms.

Saponins are triterpenoid or steroidal glycosides and are an important group of naturally occurring compounds of plant origin. They exhibit diverse pharmacological potentials including radical scavenging, as well as neuroprotective, anti-diabetic and anti-inflammatory activities, owing to their diverse chemical scaffolds. Saponins consist of an aglycone part (non-sugar) and a glycone part (sugar) and have at least one glycosidic (C–O sugar bond) linkage present between the glycone and aglycone mostly at C-3. On the basis of the aglycone part, saponins are classified into triterpenoid glycosides, steroid glycosides and alkaloid glycosides. Saponins exhibit neuroprotective activities against various disorders of the central nervous system (CNS) including stroke, Alzheimer’s disease (AD), Huntington’s disease (HD) and Parkinson’s disease (PD). They mediate their therapeutic effects by modulation of various pathological targets. This study highlights various neuroprotective mechanisms of saponins including free radical scavenging, modulation of neuroprotective signaling pathways, activation of neurotrophic factors, modulation of neurotransmitters, inhibition of BACE1 enzyme and tau hyper-phosphorylation. The study concludes that saponins have considerable efficacy against various pathological targets of neurological disorders, especially AD, and might be an important source of leads against neurodegenerative disorders.

Interaction of cyanidin with a hydroxylated surface (kaolin), modeling the effect of pН

The development of interest in anthocyanins in recent years is associated with an increase in the range of applications of these natural glycosides, contained in plants and berries, the color changes from red to blue with increasing pH. In addition to coloring properties (clay, fabric, hair), the use of anthocyanins – components of red and blue berries (including blueberries) – helps to reduce the risk of cardiovascular disease, Parkinson's disease and more.Most practical studies concern the interaction of anthocyanins with surfaces (clay, tissue, gastrointestinal mucosa, etc.) that have many hydroxyl groups. Therefore, the question of determining the approximate pH range is relevant, in which such an interaction is most likely. The aim of the work was to determine the priority form of the dye (according to the pH of the medium), which can be better fixed on the surface of kaolinSimulation of the interaction of cyanidin with the surface of white clay was performed by the Hartree-Fock-Rutaan method, using the GAMESS software package.The paper presents the results of modeling the interaction of different forms of the anthocyanin model – cyanidin (the content of cyanidin in plants is 50 % of the mass of all types of anthocyanins) in solutions with pH<3 (red – forms of cyanidin), 3<pH<7 (violet) and pH>7 (blue) with a hydroxylated surface of white clay – kaolin, having different types of hydroxyl groups.
 The aglycone part of the cyanidin molecule artificially was approached at a distance of approximately 2.5 Å to the surface of kaolin.
 It was shown, that the quinoid form of cyanidin (violet) was the most active of the three forms, mainly in interaction with the silanol groups of the kaolin surface. The form of cyanidin at pH<3 (red) have the lowest energies of interaction with the surface of kaolin

Environmentally benign, ultrasonication assisted, sustainable valorization for commercially important nutraceutical-Daucosterol from the heartwood of invasive Prosopis juliflora (Sw.) DC

Steroidal saponins are amphiphilic glycosidic chemical constructs, which possess diverse biological activities, that are attributable to the structural variations in the aglycone part and in the carbohydrate part. Daucosterol, a steroidal saponin, is a nutraceutical possessing various pleiotropic effects such as food preservative, immunomodulatory, anticancer and hypoglycemic effects. Non-conventional extraction methods have gained more importance as they provide target specific isolation, and thus, an eco-friendly sustainable process, optimized using Response surface methodology can be a viable proposition. P. juliflora, is an invasive plant, is seen as a major threat to agricultural lands, and is known to be a rich source for these saponins. Here we have reported a greener valorization procedure for Daucosterol from the heartwood of the invasive weed P. juliflora, various factors such as solvent, Solid-solvent ratio, extraction time, temperature, as well as aided valorization methods with microwave and ultrasonication were tested. Based on ‘one variable at a time’ experiments, which could influence the extraction process, an ultrasound-assisted valorization for daucosterol was developed. Response surface methodology was designed using a Box-Behnken method. Acetonic precipitation of Daucosterol yielded 8.02 mg/g of PJ, with the optimized conditions being 49.5 °C temperature, 14.6% solid loading and 0.76 M HCl in ethanol (v/v). It is also found that solvent had a greater influence on the extraction process. In order to understand the effect of acid treatment on the material, the cell wall constituents were quantified, and an acid-ethanol treatment method, improved the cell wall degradation and thereby increased the extraction efficiency of the nutraceutical, as evidenced by SEM images.

Chemical and Chemo-Enzymatic Syntheses of Glycans Containing Ribitol Phosphate Scaffolding of Matriglycan.

Ribitol phosphate modifications to the core M3 O-mannosyl glycan are important for the functional maturation of α-dystroglycan. Three sequentially extended partial structures of the core M3 O-mannosyl glycan including a tandem ribitol phosphate were regio- and stereo-selectively synthesized: Rbo5P-3GalNAcβ, Rbo5P-1Rbo5P-3GalNAcβ, and Xylβ1-4Rbo5P-1Rbo5P-3GalNAcβ (Rbo5P, d-ribitol-5-phosphate; GalNAc, N-acetyl-d-galactosamine; Xyl, d-xylose). Rbo5P-3GalNAcβ with p-nitrophenyl at the aglycon part served as a substrate for ribitol phosphate transferase (FKRP, fukutin-related protein), and its product was glycosylated by the actions of a series of glycosyltransferases, namely, ribitol xylosyltransferase 1 (RXYLT1), β1,4-glucuronyltransferase 1 (B4GAT1), and like-acetyl-glucosaminyltransferase (LARGE). Rbo5P-3GalNAcβ equipped with an alkyne-type aglycon was also active for FKRP. The molecular information obtained on FKRP suggests that Rbo5P-3GalNAcβ derivatives are the minimal units required as the acceptor glycan for Rbo5P transfer and may serve as a precursor for the elongation of the core M3 O-mannosyl glycan.

Saikosaponins: A Review of Structures and Pharmacological Activities

Radix Bupleuri is a traditional medicine widely used in China and other Asian countries. Phytochemistry and pharmacology study reveal that saikosaponins(SSs) are the main bioactive compounds in Radix Bupleuri. SSs are complex compounds composed of triterpene aglycone and carbohydrate part containing 1-13 monosaccharides, which can be divided into seven types based on their structural characteristics. Many different kinds of SSs have been isolated from plants of Bupleurum L. SSs show a variety of biological activities, such as central nervous system protection, liver protection, antivirus, anti-tumor, anti-inflammation, hormone-like effects, and immune regulation functions. Due to their broad activity and favorable safety profile, SSs attract an increasing amount of attention in recent years. In this review, the structures of 86 SSs are summarized based on the different aglycones due to the diverse structures of saikosaponin(SS). The pharmacological effects and related mechanism of SSs are thoroughly reviewed, and perspectives for future research are further discussed.

Evaluating the efficacy of Capparis spinosa Total flavonoids to control Bird Lice (Menacanthus stramineus)

The present study included an in-vitro and in-vivo insecticidal investigation for one of wild Iraqi plant Capparis spinosa total flavonids on locally chicken lice (Menacanthus stramineus). Extraction of total flavonoids from 115g of fresh plant samples by reflex extraction with 600ml distilled water with (10% v/ v) HCl, for 8 hours continuously and the aglycon part was obtained with ethyl acetate. The acetate layer was dried and the residue was weighted and subjected for qualitative and quantitative analysis. Three flavonoids concentrations of Capparis spinosa total Flavonoid (5,3 and 1) mg/ml in 100ml distilled water to treat a collected sample of Bird Lice (Menacanthus stramineus) in vitro and in vivo at different life stages in comparison to a traditional anti lice drug treatment permethrin (0.5mg/ml) as positive control. Distilled water application was considered as negative control. Results of present study showed that the plant was rich with different types of flavonoids and the effect of flavonoid extracts of the Capparis spinosa plant in the decimation of the different stage of chicken body lice, as the concentration factor had non-significant effect on the killing of adult and a significant effect on the killing of eggs/nymph, and this effect increased with the increase in the concentrations of the extract.

INVESTIGATION OF THE POSSIBILITY OF USING THE METHOD OF DIFFERENTIAL SPECTROPHOTOMETRY FOR THE ANALYSIS OF OVERLAPPING ABSORPTION BANDS OF TRITERPENE SAPONINS CHROMOPHORES AND THEIR QUANTITATIVE DETERMINATION IN AQUEOUS SOLUTIONS

A detailed analysis of the absorption spectra of mono- and bidesmoside triterpene glycosides was performed. It is suggested that the maximum in the region of 198–208 nm is attributed to the absorption of the double bond in the cyclohexene ring of the aglycone. The second less seen maximum at a wavelength of 280 nm is observed in the spectrum of saponin Quillaja Saponaria and is almost completely absent in the spectrum of saponin Mukorossi Sapindus. Identification of this maximum is extremely difficult, since its presence can be due to both the aldehyde group in the aglycone and the hydroxyl and carboxyl groups in the carbohydrate molecules.
 Using the method of differential spectrophotometry, a method for decomposing the UV spectrum of saponins into its constituent components is proposed and justified. A spectral analysis was performed, including the assignment of the absorption bands to the functional groups of the studied compounds. The possibility of estimating changes in the spectral properties of glycoside solutions with changes in the acidity of the medium is considered. The possibility of a bathochromic shift of the maximum absorption of the aglyconic part of saponin depending on the microenvironment (the structure of the carbohydrate part) and changes in the pH of the solution is established. It is shown that the bands at 274, 280.5 nm correspond to n-π* transitions of carbonyl and carboxyl groups and are determined only in the regions of high concentrations in Quillaja Saponaria saponin solutions. Based on the results obtained, calibration models for the quantitative determination of saponins in solutions are proposed. The regression analysis of the calibration equations is carried out, the main statistical indicators are calculated.

Studies on Natural Products Using Monoclonal Antibodies: A Review.

An immunoblotting system (“eastern blotting”) was developed for small-molecule herbal medicines like glycosides, with no conjugation function to the membrane. Briefly, the crude extracts of herb medicines were developed by thin-layer chromatography (TLC). The small-molecule herbal medicines on TLC plates were transferred to polyvinylidene fluoride (PVDF) or polyethersulfone (PES) membranes by heating. Antigen components were divided into two categories based on their function, i.e., their membrane recognizing (aglycone part) and fixing (sugar moiety) abilities. This procedure allows for the staining of only target glycosides. Double eastern blotting was developed as a further staining system for two herb medicines using a set of MAbs and substrates.

A molecular dynamics simulations study of the ionic liquid effect on the β-glucosidase active site interactions with a flavonoid glycoside

Since the ionic liquid (IL) media is an appropriate environment for the enzymatic extraction of glycosides from natural resources, a detailed molecular understanding of the effect of IL concentration on enzyme function, with a focus on enzyme-substrate interactions, is critical. The best docking pose of Quercetin-4′-O-beta-D-glucopyranoside (Q-4′) in the active site of the β-glucosidase (BGL) enzyme was determined using molecular docking methods. Since flavonoid glycosides and enzymes are soluble in imidazolium-based ILs, the aqueous 1-butyl-3-methylimidazolium chloride ([BMIM][Cl]) was used as a solvent in this study. The interactive residues of the BGL active site, as well as the types of interactions, in BGL–Q-4′ complex were then discovered using structural interaction fingerprints (SIFt) calculations. After that, the molecular perspective of the ionic liquid (IL) concentration effect on this complex and its interactions were simulated using 100 ns all-atom MD simulations. According to SIFt changes, changing the IL concentration influenced the overall interactions in the BGL–Q-4′ complex and involved residues. The RMSF findings indicated that the maximum flexibility of the interactive residues was observed in the 50% IL solution, however, flexibility changes were not high enough to alter enzyme activity. More analysis showed that solvent effects influenced hydrogen bond (HB) interactions with the substrate in both active site subsites; glycone (subsite -1) and aglycone subsites. Aromatic interactions followed a similar trend, suggesting that changes in IL concentration affected them. The solvent effects had a greater impact on the interactions with the aglycone part in both cases, which was attributed to aglycone subsite's greater solvent accessibility. Furthermore, it was found that IL concentration had a negative impact on the enzymatic hydrolysis process by influencing the formation of HB with Glu193 as well as the nucleophilic attack of Glu402. Finally, SDF findings indicated that an accumulation of IL molecules at the active site entrance could reduce enzyme activity by reducing the active site's accessibility to the substrate. By providing a molecular perspective on the BGL-substrate complex behavior in the IL system, our findings lead to a deeper understanding of the flavonoid glycoside hydrolysis process in these useful solvents.